I have invited Victor to be an Associate Researcher-Writer for this blog and expect that one or two of his first blog entries will appear online today.  Victor responded to my recent Call for associate researcher-writers by submitting a number of candidate blog entries.  Those items and correspondence with him convinced me that Victor has what it takes to extend the coverage of this blog in scope and depth while maintaining and improving its quality: in-depth knowledge of key science areas relevant to longevity, scientific integrity, an interest in scouring the ever-changing literature, a probing mind seeking to investigate new developments for their possibilities, a passion for discovery, an attention to detail,  an interest in communicating, and a capability to write clearly.  Victor’s blog entries will appear with minimum or no editing on my part.  To the extent that he offers views and opinions, they will be his own and may be different than mine.  If I feel a need to comment on anything he says I will do so via blog comments just like any other blog reader. 

We are in the midst of a long-term shift in paradigms related to the essence of how we take care of ourselves as we live until we die.  The shift is from the predominant current model which we call healthcare to a new model which I call wellness-longevity.  I contrast these models and discuss specific examples of the multiple ways in which the new model is slowly emerging.

Healthcare

“Health care is the diagnosis, treatment and prevention of disease, illness, injury, and other physical and mental impairments in humans. Health care is delivered by practitioners in medicine, chiropractic, dentistry, nursing, pharmacy, allied health, and other care providers.” Healthcare in advanced countries is mainly based on a medical model, a repair-shop model primarily focused on trying to cure people or allow them to be functional after they obviously get sick or become debilitated.  This is often an inefficient process and for many situations like age-related dementia and several cancers works poorly or not at all.   

Healthcare is an extremely large and diverse industry.   According to an overview of the healthcare industry: “The United States of America has one of the largest medical and healthcare industries in the world, followed by Switzerland and Germany. The USA’s medical industry comprises of more than 750,000 physicians and 5,200 hospitals. USA witnesses approximately 3.8 million inpatient visits and 20 million outpatients visit on a daily basis. Furthermore, the United States of America has the largest workforce i.e. one in every 11 US residents employed in the health care business.” Important additional components of the healthcare industry includes the pharmaceutical industry, many biotech companies, medical equipment manufacturers, government agencies like the National Institutes of Health and the FDA, multiple State health and regulatory agencies, health insurance companies, the armed services medical corps, and university schools of medicine, dentistry and public health.

The economics of healthcare are staggering.   “The Global prescription drug market was $550 billion in the year 2006. Also, the total health care expenditures across the world were $4.5 trillion last year. Of which, US solely account for $ 2.2 trillion, $ 2 trillion in OECD countries and remaining $ 0.3 in other countries of the world. Learn about the challenges for the medical industry in the article ‘2009 Financial Crisis: Top 9 Issues for Health Industries(ref).” “Dramatic figures in the CMS report show that health care accounted for 17.3% of the U.S. economy in 2009(ref).” (I would not be surprised if the number is now up to 20%) “The increase in health spending, from $2.34 trillion in 2008 to $2.47 trillion in 2009, was the largest one-year jump since 1960. CMS predicts total U.S. health spending in 2019 will be $4.5 trillion.” Breakdown of US national health care expenditures can be found here.

Besides becoming ever-more and more expensive and possibly unworkable, the health care model often produces poor results.  If a car is poorly maintained, by the time blue smoke is coming out of the exhaust and oil is being burned, the rings and valves in the engine could already be ruined and the car not economically repairable.  Simple maintenance and regular oil and oil filter changes can largely avert the problem.  If the body of an obese elderly person is poorly taken care of with insufficient exercise and poor diet, by the time active signs of diabetes show up the body’s metabolic systems could have so remodeled themselves that cure is impossible.  Simple preventative maintenance including a program of exercise and good diet can also frequently prevent diabetes from manifesting itself.

Wellness-longevity

Wellness-longevity is a new paradigm that subsumes health care but goes far beyond it.  It is a paradigm that has been discussed for a long time but that is only now starting to become manifest. Wellness-longevity is not focused on sickness but rather on maintenance of health and longevity.  It is comparable to preventive maintenance where steps are taken to prevent debility or sickness sufficiently in advance so that debility or sickness becomes relatively scarce.  While important aspects of wellness-longevity are captured in the traditional idea of preventative medicine, wellness-longevity goes much further in expectations for ever-enhanced longevity, personal productivity and transformed lifestyles.

Airliner safety maintenance – a working model of wellness and longevity

Prodded by governments, long ago commercial airlines industry decided to adopt a wellness-longevity model for their airplanes.   When air crashes occur it is usually because that model has not been followed diligently.  The decision to make this model universal was based on safety and economics.  If the airlines industry were to follow a model like our healthcare systems where most problems are addressed only after they became manifest, we would probably be hearing about dozens of crashed airplanes every week. 

It is useful to look at the airlines wellness-longevity model and see how it works and how effective it is.  As it turns out, many aspects of the model can be applied to human wellness-longevity.  The objective of the airliner safety program is to assure that every working airliner is a safe to fly in as a new one. Even if the aircraft is 50 years old.  So different aircraft can compete in terms of efficiency, range, comfort, etc., but are basically the same in terms of passenger safety.

Details of the wellness-longevity program for aircraft are contained in this Maintenance: Airplane and Airline FAQ.  Aspects of the program include limitations on the numbers of flights and flight hours between inspection, multiple levels of preventative maintenance including before every flight, maintenance of detailed computer records on the history of every component in the aircraft, a schedule of frequent inspections of multiple kinds, computerized logs of multiple kinds, definitions of when parts must be overhauled or replaced, documentation of every problem observed no matter how slight, multiple monitoring systems built into the aircraft, centralized reporting of problems with information shared across airlines, government-mandated upgrades and constant manufacturer improvement of components.  If and when accidents occur there is careful analysis of what happened and identification of possible corrective actions. 

Clearly there are some things in this program like stripping out all the parts and maintaining or replacing  them individually can’t be done with humans.  But many other aspects of the program may well be worth emulating.  For example: “AIRWORTHINESS DIRECTIVES (A.D.’s)  As a further double-check that the commercial airline fleet is meticulously maintained, the FAA has set up an information system where maintenance reliability data can be shared by the airlines. If certain important components of an aircraft such as the engines, flight controls, hydraulic system, brakes, etc. should fail during flight, the individual airline must notify the FAA, which forwards the data to all airlines. This serves as an alert to the airlines so their inspection schedule can be altered as necessary. If another failure should occur with that same component, the FAA can order a mandatory change in the inspection timetable by issuing an Airworthiness Directive. Regardless of how soon the next preventive maintenance or overhaul is scheduled, an A.D. requires immediate action in the time allowed by the FAA, even if it requires removing an airplane from service. If an unsafe condition exists, an A.D. will be issued that will ground an entire fleet of airplanes, until a safe fix can be found(ref).” 

Despite these rules, adherence to them by different airlines vary.  Five-year safety records for different airlines can be found here.  The main point is that even for the worst airlines, air travel is by far the safest form of travel on a per-mile basis.  Accidents are very rare and not the norm.  This chart shows how the vast majority of important airlines in the world have not had a fatal accident in the last 10 years.  Why can’t we do something like this for people?  I am convinced we can and will and are already started on the way to getting there.

 A human model for wellness-longevity

 What the human model for wellness-longevity will look like in the long term is unknown.  I have, however, already provided a fairly thorough vision of it in the recent blog entry The 2011 Bio-IT World Conference & Expo – On the way to Personalized Predictive Preventative Participatory Medicine and in last  year’s blog entry Harnessing the engines of finance and commerce for life-extension.  Reading those blog entries you will see that there is a striking similarity to what I envisage and what the airlines are doing:  pursuing a healthy lifestyle in every regard, regular preventative maintenance, maximum use of information systems, maintaining very detailed personalized records (whether personalized to an individual or to a specific aircraft), strictly following a number of wellness regimens, identification and use of biomarkers (performance and wear indicators in the case of aircraft parts),  widespread sharing of information, sharing of information among relevant parties (hospitals, patients, doctors for people, different airlines; manufacturers and government agencies for aircraft), prompt analysis of breakdowns and warnings to others, etc.

The benefits of going beyond healthcare to wellness-longevity paradigm

The healthcare paradigm by itself is broken, obsolete, and produces poor results.   Despite the fact that the US spends more per capita on healthcare than leading European countries that put somewhat more emphasis on wellness, we trail those countries miserably in multiple measures of health and trail them in longevity.  See the blog US falling behind in longevity increases – why?    Curing diseases after they occur is vastly more difficult than preventing disease occurrences in the first place.  Further, many diseases themselves create multiple forms of collateral damage, particularly in elderly patients.  So a serious disease late in life often leads to a down-hill cascade of events leading soon to disability and death.  And many diseases of old age like Alzheimer’s disease have proven themselves to be resistant to the possibility of “cure” despite tens of billions of dollars spent researching them.

For individuals, benefits of moving to the new paradigm are a longer healthier life.  For health plans and health insurance companies, immediate benefits include drastically lowered health care costs.  The same is true for state and federal governments and for corporations that provide health care coverage for employees.  And along with lowered health care costs go increased productivity of healthier longer-lived people. 

Examples of the emerging wellness-longevity paradigm

Expressions of the new wellness-longevity paradigm are showing up in multiple forms.  I mention only a few of the many things happening.

SilverSneakers

 “The SilverSneakers® Fitness Program is an innovative health, exercise and wellness program helping older adults live healthy, active lifestyles.”  The program is offered through health plans. “The Silver Sneakers Fitness Program brings yoga, Pilates, aquatic and cardio circuit classes to older Americans at 10,000 locations in 50 states. “We have done a lot to educate,” said Stephanie Wong, spokesperson for Silver Sneakers. “Particularly among 70- and 80-year olds who have not been members of a gym, it’s a whole new ball game.”  Brain booster exercises are also on the menu for the Silver Sneaker participant, whose average age is 72. “The longer you can be independent, the more successfully you’re going to age,” Wong said. “If you prevent falling you avoid being transitioned into a senior centre. Physical activity promotes brain health. Recent studies support that(ref).”

  “SilverSneakers is a fun, energizing program that helps older adults take greater control of their health by encouraging physical activity and offering social events. — Unlock the door to greater independence and a healthier life with SilverSneakers. Health plans around the country offer our award-winning program to people who are eligible for Medicare or to group retirees. SilverSneakers provides a fitness center membership to any participating location across the country. This great benefit includes:

·        access to conditioning classes, exercise equipment, pool, sauna and other available amenities

·        customized SilverSneakers classes designed exclusively for older adults who want to improve their strength, flexibility, balance and endurance

·        health education seminars and other events that promote the benefits of a healthy lifestyle

·        a specially trained Senior AdvisorSM at the fitness center to introduce you to SilverSneakers and help you get started

·        member-only access to online support that can help you lose weight, quit smoking or reduce your stress

·        SilverSneakers Steps for members without convenient access to a location(ref)”

Let’s Move

Lest it be thought that the emerging wellness-longevity paradigm is concerned only with seniors Let’s Move is a fitness thrust oriented to children.  Let’s Move is a campaign designed to reduce the incidence of childhood obesity being promoted by Michelle Obama.  As such it is oriented to people at the opposite end of age demographics.  It is concerned with promotion of healthy food and nutrition as well as regular exercise as tools for preventing obesity and creating a healthier generation of younger Americans at all economic levels. 

PreventObesity.net

 PreventObesity.net is an initiative designed to foster networking to support the prevention of childhood obesity. “We offer free services to support leaders and organizers as you work to change policies and environments to help children and families eat well and move more, especially in communities at highest risk for obesity.” – “Driven by a belief that technology offers an opportunity to tap the talents, creativity, expertise and energy of potential collaborators, the Robert Wood Johnson Foundation (RWJF) launched PreventObesity.net to harness the power of online networks to reverse the childhood obesity epidemic.

 Netcentric

RWJF has engaged with Netcentric Campaigns to create and implement networking strategies that support the Foundation, the Robert Wood Johnson Foundation Center to Prevent Childhood Obesity, other RWJF-funded national programs and others working in the field. Netcentric has supported other health-related online campaigns such as the Health Care for America Now (HCAN) campaign.

Entrepreneurial ventures

Because of institutional rigidities, the new wellness-longevity paradigm may be moved along swiftly by entrepreneurial ventures.  Here are a few examples:

23andMe

23andme is a $207 personal genotyping service oriented toward ordinary people and the wellness rather than the healthcare market.  Using a DNA chip, the service scans the saliva of a customer to look for the presence of about a million SNPs that are spread across the entire genome. “A single-nucleotide polymorphism (SNP, pronounced snip) is a DNA sequence variation occurring when a single nucleotide — A, T, C, or G — in the genome (or other shared sequence) differs between members of a biological species or paired chromosomes in an individual(ref)”  The SNPs looked for are ones known to be “tag” SNPs correlated with ones that have important disease, hereditary and other associations.  “23andMe is a retail DNA testing service providing information and tools for consumers to learn about and explore their DNA. We utilize the Illumina OmniExpress Plus Research Use Only Chip which has been customized for use in all of our products and services by 23andMe. All of the laboratory testing for 23andMe is done in a CLIA-certified laboratory.”  Among things scanned for are carrier status for 24 inherited conditions, 19 kinds of drug responses, 50 traits and disease risk for 100 conditions.  Output is a personalized profile with much interpretative and educational material. 

The 23andMe service includes a one-year Personal Genome Service  subscription which includes updates about yourself, browsable raw data, discounts on future platforms, secure storage, and alerts when relatives are discovered.   

The 23andMe service is careful to point out that the genotyping does not constitute a diagnostic test: a) because the 23andme service it is not FDA approved, b) because the gene chips involved are less reliable than much more expensive ones, c) because the number of SNPs scanned for is a small fraction of those known to show up in the whole human genome, d) because many of the disease and other associations indicated by the presence of SNPs are weak indicating only a probabilistic propensity,  and perhaps most critically, e) because interpretations of SNPs are only as good as the association studies that provide such interpretations.  Rather, 23andMe is a direct-to-consumer wellness-longevity service that is in the genotyping area where the medical profession has been slow to respond.

MDVIP

MDVIP is a network of primary care doctors who deliver both personalized wellness services as well as conventional medical services in a service model defined by MDVIP.  Current membership includes 450 doctors in 33 states.  While an average family practitioner may have 2,400 patients, MDVIP limits the load to 600 patients per doctor and requires all participating doctors to follow its model.  Focus is on personalized care, detection and early prevention.   “When it comes to your health, you deserve an equal partner. — With the right support, you have the power to transform your life. That’s why at MDVIP, we’ve created a unique approach to healthcare that puts you, your health and your needs first. You’ll have the chance to create a strong, compassionate partnership with your personal doctor – a relationship that will help you reach your wellness goals and become an advocate for healthy living in your community. — Our approach departs from traditional healthcare systems that reward doctors for seeing as many patients as possible. Instead, we give your doctor the time and freedom to get to know you, your lifestyle and your current health. He or she can then offer you carefully thought out, comprehensive health plans with long-term health benefits. Your doctor can follow up with you on a regular basis to help prevent any new medical issues from going undetected.”  Patients pay from $1,500 to $1,800 per year to their MDVIP doctor for wellness services not covered by insurance.  This makes joining MDVIP attractive to primary care doctors who tend to be overworked and underpaid when compared to their medical-specialty peers. 

Apparently the MDVIP model is successful in both providing wellness and reducing medical costs, reducing hospital utilization by 75% in the case of medicare patients, reducing hospital utilization by 65% in the case of privately-insured patients.  This is according to information provided me by MDVIP. I plan to do a separate blog entry on MDVIP. 

Shape up the nation

The web service shapeupthenation.com seeks to utilize social networking for personal achievement of health objectives.  The concept is connecting with people you trust to help you fulfill your health goals.  “Shapeupthenation offers a web platform that can be used by health plans to achieve a number of objectives including “Embrace Social Networking: Health plans across the nation are trying to figure out their social networking strategy. Our platform harnesses the power of trusted social networks to help you achieve your business objectives using the latest and most innovative technology. Don’t keep putting it off — it’s time to get started. — Engage Members: Healthy, engaged members are every health plan’s dream. Let us help you build positive relationships with your members and bring them together with your company as the central partner in their health.  Build Value for Employers: Your employer groups are desperately seeking ways to control rising health care costs and boost morale, productivity, and retention. Help them by offering a proven way to change employee behavior and transform company culture.  Reduce Costs: Our evidence–based program is proven to help members increase exercise and lose weight. In fact, a recent study shows that the average participant loses one Body Mass Index point, which translates to a $202.30 reduction in claims annually.  Help Community: Some health plans are looking beyond their current membership and wondering how they can play a role in helping to promote healthy lifestyles on a community–wide basis. We have experience in running large–scale community wellness programs and can do the same for you.”

Smartphone apps

Perhaps nowhere can small-scale entrepreneurial initiatives for wellness-longevity be seen more dramatically than in the swelling list of health-fitness apps for iPhones and Android phones.  There are hundreds of such apps out there, mainly supported by small entrepreneurial companies. 

Smartphones have orientation and motion sensors that can help determine your kinds and levels of movement.  They have GPS and cell-tower location sensing that allows you, for example, to track an exercise path in the woods.  They have cameras that can be used to read bar codes on food packages and monitor heart rates.  And they have Bluetooth capability that enables them to link to Bluetooth-enabled body sensors.  They can listen to and interpret what you say and talk back to you.  They are usually with you.  They can keep you in constant connection with multiple health databases. And the data related to the apps are available both wirelessly and online via computers and tablet devices.

I find these apps fascinating and plan to do a blog entry on them in the near future.  For now, Android health and fitness marketplace apps are here.  You can check out the “8 best android apps for health and fitness,” the “50 Coolest Fitness and Health Apps for the iPhone,”  and “100 Fabulous iPhone Apps for Your Health and Fitness.” Yesterday, I started using a couple of apps on my Google Android phone, both of which were downloaded for free.  One is called Myfitnesspal, an application allows the user to set and track weight goals by detailed monitoring of daily diet and exercise.   It knows calorie contents of many foods.  Online access is available either via computer or Android phone.  Another amazing app I have started using measures heart rate using your my phone’s camera.  It is called Instant Heart Rate and has been downloaded 250,000 times.

We are in interesting times!  I invite my blog readers to comment on these and other wellness-longevity initiatives you may find to be particularly interesting.

Multiple factors are implicated in age-related physical brain changes and normal decline of memory and brain functioning.  Continuing research is clarifying the relationships among these factors with new insights coming into focus.  I report here on some of those relationships as well as interventions that can avert or even possibly reverse age-related cognitive or memory decline.  This blog entry particularly deals with what is going on in the aging hippocampus and links up a number of topics I have discussed previously in this blog and in my longevity treatise –  neurogenesis,  BDNF, exercise, resveratrol, and curcumin. 

About the hippocampus and aging

“The hippocampus is a major component of the brains of humans and other mammals. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Like the cerebral cortex, with which it is closely associated, it is a paired structure, with mirror-image halves in the left and right sides of the brain. In humans and other primates, the hippocampus is located inside the medial temporal lobe, beneath the cortical surface.  It contains two main interlocking parts: Ammon’s horn and the dentate gyrus. — Since different neuronal cell types are neatly organized into layers in the hippocampus, it has frequently been used as a model system for studying neurophysiology. The form of neural plasticity known as long-term potentiation (LTP) was first discovered to occur in the hippocampus and has often been studied in this structure. LTP is widely believed to be one of the main neural mechanisms by which memory is stored in the brain. (ref).”

Brain cell renewal depends on neurogenesis due to differentiation of neural stem cells mainly in the hippocampus and cell migration.  The process goes on throughout life.

The rate of neurogenesis tends to decline with aging and maintenance of an adequate level of neurogenesis is another important consideration in keeping an aging brain vital. 

From the August 2010 blog post Neurogenesis, curcumin and longevity: “An introductory discussion of neurogenesis can be found in my treatise in the section on the Neurological degeneration theory of aging. “Increasing research evidence suggests that maintaining a sufficient and consistent rate of neurogenesis in the brain, particularly in the hippocampus, is important for the maintenance of cognitive health. Insufficient or irregular neurogenesis is thought to be a causative factor in bipolar disease and other mood disorders. Neurogenesis takes place throughout the life of a mammal in two major brain structures: the dentate gyrus of the hippocampus and the subventricular zone of the forebrain. In these regions neural progenitor cells continuously divide and give birth to new neurons and glial cells. In the mammalian brain neural progenitor cells are multipotent. They can differentiate into neurons, astrocytes or oligodendrocytes, though the factors that determine differentiation are poorly understood. The rate of neurogenesis tends to decline with advancing age in old mammals, as well as the does the number of functional neurons.”

The 2009 publication Endogenous regulation of neural stem cells in the adult mammalian brain relates: “Tissue-specific stem cells replenish organs by replacing cells lost due to tears and wears or injury throughout life. Long considered as an exception to this rule, the adult mammalian brain has consistently been found to possess stem cells that ensure neurogenesis. Neural stem cells persist within the subventricular zone bordering the lateral ventricles of the brain. Constitutively, neural stem cells proliferate and produce a continuous supply of new neurons that migrate towards the olfactory bulb where they ensure turnover of interneurons. Owing to their potential clinical use for the treatment of neurodegenerative diseases, the factors that control proliferation, self-renewal and differentiation of neural stem cells have received increasing interest. These studies have unraveled that the cellular dynamic within the subventricular zone is tightly controlled by astrocytes and endothelial cells that neighbor neural stem cells. These neighboring cells produce substrate-bound and soluble factors that make up a specialized microenvironment named the neurogenic niche. The equilibrium between neural stem cells activity and quiescence is adjusted by neurons located in remote brain areas that adapt neuron production to physiological and pathological constraints. Brain injury or neurodegenerative diseases affect neural stem cells proliferation, differentiation and migration suggesting that neural stem cells are involved in brain self-repair. Understanding the endogenous mechanisms that regulate neural stem cells will help to replenish cellular constituents lost by injury and thereby allow an effective development of neural stem cells based therapies of brain diseases.”

The 2009 publication Cell migration in the normal and pathological postnatal mammalian brain relates “In the developing brain, cell migration is a crucial process for structural organization, and is therefore highly regulated to allow the correct formation of complex networks, wiring neurons, and glia. In the early postnatal brain, late developmental processes such as the production and migration of astrocyte and oligodendrocyte progenitors still occur. Although the brain is completely formed and structured few weeks after birth, it maintains a degree of plasticity throughout life, including axonal remodeling, synaptogenesis, but also neural cell birth, migration and integration. The subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampus are the two main neurogenic niches in the adult brain. Neural stem cells reside in these structures and produce progenitors that migrate toward their ultimate location: the olfactory bulb and granular cell layer of the DG respectively. The aim of this review is to synthesize the increasing information concerning the organization, regulation and function of cell migration in a mature brain. In a normal brain, proteins involved in cell-cell or cell-matrix interactions together with secreted proteins acting as chemoattractant or chemorepellant play key roles in the regulation of neural progenitor cell migration. In addition, recent data suggest that gliomas arise from the transformation of neural stem cells or progenitor cells and that glioma cell infiltration recapitulates key aspects of glial progenitor migration. Thus, we will consider glioma migration in the context of progenitor migration. Finally, many observations show that brain lesions and neurological diseases trigger neural stem/progenitor cell activation and migration toward altered structures. The factors involved in such cell migration/recruitment are just beginning to be understood. Inflammation which has long been considered as thoroughly disastrous for brain repair is now known to produce some positive effects on stem/progenitor cell recruitment via the regulation of growth factor signaling and the secretion of a number of chemoattractant cytokines. This knowledge is crucial for the development of new therapeutic strategies. One of these strategies could consist in increasing the mobilization of endogenous progenitor cells that could replace lost cells and improve functional recovery.”

The April 2011 publication Adult Neural Stem Cells: Response to Stroke Injury and Potential for Therapeutic Applications reports “The plasticity of neural stem/progenitor cells allows a variety of different responses to many environmental cues. In the past decade, significant research has gone into understanding the regulation of neural stem/progenitor cell properties, because of their promise for cell replacement therapies in adult neurological diseases. Both endogenous and grafted neural stem/progenitor cells are known to have the ability to migrate long distances to lesioned sites after brain injury and differentiate into new neurons. Several chemokines and growth factors, including stromal cell-derived factor-1 and vascular endothelial growth factor, have been shown to stimulate the proliferation, differentiation, and migration of neural stem/progenitor cells, and investigators have now begun to identify the critical downstream effectors and signaling mechanisms that regulate these processes. Both our own lab and others have shown that the extracellular matrix and matrix remodeling factors play a critical role in directing cell differentiation and migration of adult neural stem/progenitor cells within injured sites. Identification of these and other molecular pathways involved in stem cell homing into ischemic areas is vital for the development of new treatments. To ensure the best functional recovery, regenerative therapy may require the application of a combination approach that includes cell replacement, trophic support, and neural protection.”

With aging there is normally a decline in the volume of the hippocampus along with a decline in memory and brain processing capability.  However, such declines appear not to be universal and may be averted.

The 2010 publication Involvement of BDNF in age-dependent alterations in the hippocampus reports.”It is known since a long time that the hippocampus is sensitive to aging. Thus, there is a reduction in the hippocampal volume during aging. This age-related volume reduction is paralleled by behavioral and functional deficits in hippocampus-dependent learning and memory tasks. This age-related volume reduction of the hippocampus is not a consequence of an age-related loss of hippocampal neurons. The morphological changes associated with aging include reductions in the branching pattern of dendrites, as well as reductions in spine densities, reductions in the densities of fibers projecting into the hippocampus as well as declines in the rate of neurogenesis.”

Brain-derived neurotrophic factor (BDNF) is a factor critically involved in the regulation of age-related processes in the hippocampus including loss of hippocampal volume.

The previously-mentioned publication reports “In this review it is hypothesized that brain-derived neurotrophic factor (BDNF) is a factor critically involved in the regulation of age-related processes in the hippocampus. Moreover, evidences suggest that disturbances in the BDNF-system also affect hippocampal dysfunctions, as e.g. seen in major depression or in Alzheimer disease.” For background on BDNF see my March 2010 blog entry BDNF gene – personality, mental balance, dementia, aging and epigenomic imprinting.  That blog entry discusses BDNF in relationship to dementia, mental balance, aging, mental exercise and epigenetics.

The 2010 publication   Brain-derived neurotrophic factor is associated with age-related decline in hippocampal volume relates “Hippocampal volume shrinks in late adulthood, but the neuromolecular factors that trigger hippocampal decay in aging humans remains a matter of speculation. In rodents, brain-derived neurotrophic factor (BDNF) promotes the growth and proliferation of cells in the hippocampus and is important in long-term potentiation and memory formation. In humans, circulating levels of BDNF decline with advancing age, and a genetic polymorphism for BDNF has been related to gray matter volume loss in old age. In this study, we tested whether age-related reductions in serum levels of BDNF would be related to shrinkage of the hippocampus and memory deficits in older adults. Hippocampal volume was acquired by automated segmentation of magnetic resonance images in 142 older adults without dementia. The caudate nucleus was also segmented and examined in relation to levels of serum BDNF. Spatial memory was tested using a paradigm in which memory load was parametrically increased. We found that increasing age was associated with smaller hippocampal volumes, reduced levels of serum BDNF, and poorer memory performance. Lower levels of BDNF were associated with smaller hippocampi and poorer memory, even when controlling for the variation related to age. In an exploratory mediation analysis, hippocampal volume mediated the age-related decline in spatial memory and BDNF mediated the age-related decline in hippocampal volume. Caudate nucleus volume was unrelated to BDNF levels or spatial memory performance. Our results identify serum BDNF as a significant factor related to hippocampal shrinkage and memory decline in late adulthood.”

“Changes in the concentration of brain-derived neurotrophic factor (BDNF) might be contributing to shrinkage of the hippocampus in late adulthood. BDNF, a molecule that is highly concentrated in the hippocampus (Murer et al., 2001; Phillips et al., 1990; Wetmore et al., 1990), is important in synaptic plasticity (Figurov et al., 1996; Kang & Schuman, 1995; Pang et al., 2004; Stoop & Poo, 1996; Tanaka et al., 2008) and is thought to contribute to neurogenesis in the dentate gyrus (Benraiss et al., 2001; Pencea et al., 2001; Takahashi et al., 1999), but its concentration declines in late adulthood (Lommatzsch et al., 2005; Ziegenhorn et al., 2007, however see Lapchak et al., 1993). Smaller hippocampal volumes predict more rapid conversion to dementia (Grundman et al., 2002) and poorer memory function (Erickson et al., 2009) (ref).”

Polymorphisms in the BDNF gene can be associated with mental disorders and such changes can also affect hippocampus volume

The above-mentioned blog entry discusses how the Val66Met polymorphism of the BDNF gene can affect mental states and dementia. 

“In humans, a single nucleotide polymorphism in the BDNF gene affects the regulated secretion of BDNF in the hippocampus (Egan et al., 2003) and has been related to lower serum levels of BDNF (Ozan et al., 2010) and smaller hippocampal volumes (Bueller et al., 2006; Pezawas et al., 2004; Szeszko et al., 2005)—RESULTS Hippocampal, but not caudate nucleus volume, declines with increasing age.  Consistent with prior research (e.g. Raz et al., 2005), hippocampal volume declined with advancing age after adjusting for total intracranial volume and sex. — Spatial memory performance declines with increasing age — Larger hippocampal volumes were positively associated with spatial memory performance — BDNF is positively related to spatial memory performance — we found that increasing age was associated with reduced levels of BDNF, and reduced levels of BDNF were related to both decline in hippocampal volume and elevated memory deficits.  — Interestingly, the mediation results of the hippocampus on age-related memory decline were relatively specific to the left hippocampus, and not to the right. Other studies have reported asymmetries in the volume and function of the left and right hippocampus (Erickson et al., 2009) and suggest that the left and right hemispheres might play different, but complementary roles, in memory tasks that emphasize speed. Our results suggest that the left hippocampus is related to measures of speed for all memory set sizes, and the right hippocampus only for the 3-item condition(ref).”

Exercise causes upregulated expression of BDNF leading to increase in hippocampus size and memory improvement

The 2011 publication Exercise training increases size of hippocampus and improves memory reports “The hippocampus shrinks in late adulthood, leading to impaired memory and increased risk for dementia. Hippocampal and medial temporal lobe volumes are larger in higher-fit adults, and physical activity training increases hippocampal perfusion, but the extent to which aerobic exercise training can modify hippocampal volume in late adulthood remains unknown. Here we show, in a randomized controlled trial with 120 older adults, that aerobic exercise training increases the size of the anterior hippocampus, leading to improvements in spatial memory. Exercise training increased hippocampal volume by 2%, effectively reversing age-related loss in volume by 1 to 2 y. We also demonstrate that increased hippocampal volume is associated with greater serum levels of BDNF, a mediator of neurogenesis in the dentate gyrus. Hippocampal volume declined in the control group, but higher preintervention fitness partially attenuated the decline, suggesting that fitness protects against volume loss. Caudate nucleus and thalamus volumes were unaffected by the intervention. These theoretically important findings indicate that aerobic exercise training is effective at reversing hippocampal volume loss in late adulthood, which is accompanied by improved memory function.”  The effect is not a large one but is still significant.”

One mechanism that may be involved in increasing brain volume through exercise may be the increased expression of BDNF brought about by exercise.  The positive effect of exercise on BDNF expression has been noted for some time, for example in the 2002 publication Voluntary Exercise Induces a BDNF-Mediated Mechanism That Promotes Neuroplasticity.  Another is Endurance training enhances BDNF release from the human brain.

In the recent blog entry PQQ – activator of PGC-1alpha, SIRT3 and mitochondrial biogenesis I discussed how the supplement substance PQQ encourages mitochondrial biogenesis emulating exercise in that regard, and is neuroprotective. PQQ works via mitochondria by upregulating expression of the PGC-1alpha gene and expression of the SIRT3 gene.  I looked hard at the literature to see what I could find out about interaction of the BDNF and PGC-1alpha/SIRT3 exercise-related pathways.  I discovered little, however, and it appears that the pathways probably function independently but possibly synergistically.

The blog post BDNF gene – personality, mental balance, dementia, aging and epigenomic imprinting point out how mental exercise also stimulates expression of BDNF and longevity.  See too the blog posts Mental exercise and dementia in the news again and Brain fitness, Google and comprehending longevity .

Cognitive and memory decline with age is not inevitable and can be influenced by many factors including diet and exercise.

Maintaining neuronal and cognitive plasticity is important for averting age-related memory decline and cognitive aging. 

The November 2010 publication Neuronal and Cognitive Plasticity: A Neurocognitive Framework for Ameliorating Cognitive Aging relates: “Neuronal plasticity (e.g., neurogenesis, synaptogenesis, cortical re-organization) refers to neuron-level changes that can be stimulated by experience. Cognitive plasticity (e.g., increased dependence on executive function) refers to adaptive changes in patterns of cognition related to brain activity. We hypothesize that successful cognitive aging requires interactions between these two forms of plasticity. Mechanisms of neural plasticity underpin cognitive plasticity and in turn, neural plasticity is stimulated by cognitive plasticity. We examine support for this hypothesis by considering evidence that neural plasticity is stimulated by learning and novelty and enhanced by both dietary manipulations (low-fat, dietary restriction) and aerobic exercise. We also examine evidence that cognitive plasticity is affected by education and training. — Across a range of species – rats, monkeys, and humans – a sizeable subset of older individuals do not succumb to cognitive or brain decline (Willis and Schaie, 1986; Rapp and Amaral, 1991; Gallagher et al., 1993; Lee et al., 1994; Glisky et al., 2001). Moreover, even in old age the brain remains capable of plasticity – ability to change neurons and networks in response to experience (Kleim et al., 2003). The apparent persistence of plasticity late in life may provide some protection against age-related cognitive decline.”

The relationship between age-related brain shrinkage and cognitive capability is not clear

Continuing from the same publication: “The neural substrate of cognitive aging is not understood. Although cortical shrinkage occurs with age, such shrinkage is unrelated to cognitive change. Several research groups have attempted to relate regional cortical shrinkage to longitudinal cognitive change and found either an inverse relation or no relation (Rodrigue and Raz, 2004; Van Petten, 2004; Van Petten et al., 2004). Looking longitudinally over 5 years, shrinkage in neither hippocampus nor prefrontal cortex was related to cognitive change over the same period. Only shrinkage in entorhinal cortex, known to be the initial site of pathology of AD, was related to memory change (Rodrigue and Raz, 2004). Similarly, neuron loss in aging is minimal. Although for many years, age-related neuron loss was reported, the use of newer, un-biased, stereological techniques for counting neurons revealed no significant neuron loss in old age (reviewed in (Morrison and Hof, 1997). Although cross-sectional studies show near linear decline in many cognitive functions from young to old adulthood (Park et al., 2002), white matter actually increases over the same age range (Bartzokis, 2004). Synapse loss occurs only late in life after age 65 or so (reviewed in Masliah et al., 2006) and is reversible (reviewed in Greenwood, 2007). Effects of aging on biophysical properties of neurons are selective and subtle, seen only in specific brain regions and cell types (Burke and Barnes, 2006). Dopamine neurotransmission has been found to influence working memory performance, in a way that varies with age but also varies with cognitive performance regardless of age (Volkow et al., 1998; Backman et al., 2000). Thus, the substrate of cognitive aging is not known. One source of the difficulty in relating brain structure to cognitive change in old age may be the brain’s ability to adapt. In light of evidence that plastic changes leading to improved function after training can occur even following stroke (Taub et al., 2002; Ro et al., 2006), plastic changes may be ongoing, even in the face of cortical shrinkage and white matter damage. As reviewed below, there is evidence for such adaptation in old age in the heightened activation of cortical regions supporting executive resources, claimed to occur as compensation (Grady, 1996; Grady et al., 2005; Wingfield and Grossman, 2006).”

Exercise enhances neurogenesis and synaptic plasticity

Continuing: “ Animal work has consistently shown that physical exercise increases proliferation and survival of new neurons in the dentate gyrus of the hippocampus of adults (Gould et al., 1999; van Praag et al., 1999; Lou et al., 2008; Naylor et al., 2008). Rodents given access to a running wheel typically voluntarily run as much as 3–8 km per night and this is associated with a doubling or tripling of the number of newborn cells in the subventricular zone of the dentate gyrus where neurogenesis occurs. Voluntary wheel running over long periods of time is also associated with an increase in survival of later-stage progenitor cells and newly-formed (early post-mitotic) neurons in mouse dentate gyrus (Kronenberg et al., 2006). After experimental stroke, voluntary running enhanced progenitor cell survival in dentate gyrus in mice (Luo et al., 2007). This effect may extend beyond the hippocampus, as running rats also showed significantly higher number of cholinergic neurons in the diagonal band of Broca (Ang et al., 2003). — Some of the benefits of exercise on learning may be attributable to its effects on mechanisms of synaptic plasticity. LTP, which is a durable increase in the strength of a synapse after being repeatedly stimulated, appears to be the basis for memory formation, in that it can be induced by learning alone (Whitlock et al., 2006). In the dentate gyrus of the hippocampus, benefits of exercise have been observed on both neurogenesis (Pereira et al., 2007) and LTP (Farmer et al., 2004). Finally, exercise also alters the length and complexity of dendrites and of the density of the spines found on dendrites (Eadie et al., 2005). These exercise-induced dendritic changes can improve the efficiency of communication between neurons.”

The discussion in the publication goes on to point out that factors favoring brain plasticity include many of the “usual suspect” healthy lifestyle and dietary patterns and supplements that I have discussed in multiple past blog entries including confronting daunting mental challenges, avoidance of dietary fat, adherence to a Mediterranean-type diet , and taking omega-3 fatty acids and  resveratrol.

Curcumin is also a powerful promoter of neurogenesis in the hippocampus

The August 2010 blog entry Neurogenesis, curcumin and longevity is specifically concerned with the impact of the dietary supplement curcumin on neurogenesis in the hippocampus and the impact of curcumin neural plasticity.

All behavioral experience as well as lifestyle patterns are reflected in epigenetic records which impact neuron and synapse formation in the hippocampus

I have written frequently about the all-pervasive effects of epigenetic records in the aging process.  A specific discussion of such an effect is provided in the 2010 publication Synaptogenesis in adult-generated hippocampal granule cells is affected by behavioral experiences.  “Adult-generated hippocampal immature neurons play a functional role after integration in functional circuits. Previously, we found that hippocampus-dependent learning in Morris water maze affects survival of immature neurons, even before they are synaptically contacted. Beside learning, this task heavily engages animals in physical activity in form of swimming; physical activity enhances hippocampal neurogenesis. In this article, the effects of training in Morris water maze apparatus on the synapse formation onto new neurons in hippocampus dentate gyrus and on neuronal maturation were investigated in adult rats. — The main result we found was the anticipated appearance of GABAergic synapses at 6 days in learner, cued and swimmer rats, supported also by immunohistochemical result. Swimmer rats showed the highest percentage of GFP-positive neurons with glutamatergic response at 10 and 12 days postmitosis. Moreover, primary dendrites were more numerous at 7 days in learner, cued and swimmer rats and swimmer rats showed the greatest dendritic tree complexity at 10 days. Finally, voltage-dependent Ca(2+) current was found in a larger number of newborn neurons at 7 days postinfusion in learner, cued and swimmer rats. In conclusion, experiences involving physical activity contextualized in an exploring behavior affect synaptogenesis in adult-generated cells and their early stages of maturation.”

The 2010 publication An epigenetic hypothesis of aging-related cognitive dysfunction suggests “a new hypothesis for the role of epigenetic mechanisms in aging-related disruptions of synaptic plasticity and memory. Epigenetics refers to a set of potentially self-perpetuating, covalent modifications of DNA and post-translational modifications of nuclear proteins that produce lasting alterations in chromatin structure. These mechanisms, in turn, result in alterations in specific patterns of gene expression. Aging-related memory decline is manifest prominently in declarative/episodic memory and working memory, memory modalities anatomically based largely in the hippocampus and prefrontal cortex, respectively. The neurobiological underpinnings of age-related memory deficits include aberrant changes in gene transcription that ultimately affect the ability of the aged brain to be “plastic”. The molecular mechanisms underlying these changes in gene transcription are not currently known, but recent work points toward a potential novel mechanism, dysregulation of epigenetic mechanisms. This has led us to hypothesize that dysregulation of epigenetic control mechanisms and aberrant epigenetic “marks” drive aging-related cognitive dysfunction.”  The article focuses on “reviewing current knowledge concerning epigenetic molecular mechanisms, as well as recent results suggesting disruption of plasticity and memory formation during aging.”

Wrapping it up

·        There are several important changes in human brains that typically start in middle age and that accelerate with advancing age: hippocampus size decreases, BDNF expression decreases, there is significant shrinkage of gray matter; there is a decrease in neurogenesis and often but not always decrease in cognitive capability and loss of memory.

·        Shrinking of the hippocampus, the prefrontal cortex, entorhinal cortex, and caudate nucleus in late adulthood are thought to contribute to the patterns of cognitive and memory decline often observed in older adults.

·         Age-related loss of neurogenesis is thought to be a main factor leading to age-related decline.  Neurogenesis in the brain is a tightly controlled lifelong process.  It primarily takes place in neurogenic niches in parts of the hippocampus.  New neurons migrate to their destination locations. 

·        Disorders in BDNF gene expression are implicated in many aberrant mental conditions and Alzheimer’s disease.  BDNF expression decreases with age and age-related loss in BDNF expression is thought to lead to hippocampal shrinking with age.

·        Maintaining neuronal and cognitive plasticity is important for averting age-related memory decline and cognitive aging.

·        Cognitive and memory decline with age is not inevitable and can be influenced by many factors.   Neurogenesis, BDNF expression and synaptic plasticity are highly dynamic processes in healthy individuals.  They can be upregulated with physical and mental exercise, good lifestyle patterns, via good diet and via taking certain supplements including resveratrol, curcumin and omega3 fatty acids.

·        Epigenetic regulation of brain aging is a new topic that I expect will attract significant attention as time progresses, revealing the behavior-driven gene-activation mechanisms that affect brain aging and the mechanisms that inhibit such aging. 

·        Besides the materials discussed here, a search of the index of this blog will reveal many additional articles on the key topics discussed here as well as many related topics such as Alzheimer’s disease.

I intend to keep researching and writing interesting new entries for this blog.  And I would also like to see a greater frequency of blog entries to keep up with what is going on related to aging sciences.  To accomplish this and to fulfill the Mission implied by the new blog name Aging Sciences, I need help. 

Back in February in the blog entry The evolution of my perspective as a longevity scientist, I wrote “I am not sure how much longer I can keep up with the central research developments relevant to longevity.  The pace of research is increasing and many of the key discoveries are increasingly technical.  I have had to be more selective in picking topics for blog entries.  And I am struggling harder and harder to understand what is going on in the areas of some of my blog entries(ref).”  In a comment the reader Peter had to say “Vince, you mention the difficulty in keeping up with the research which pertains to each potential cause of aging. I wonder if you have given thought to farming some of this out? For example, if you had a small team (2 to 6) of like-minded people who each agreed to take on one or two theories/pathways to stay on top of, and to distill the information down into clearly written living summaries (complete with sourcing) it might go along ways to allowing you to have the time to integrate all of this into a meaning full whole and step back enough to see patterns and interconnection among the theories/pathways.”

I think Peter’s suggestion is excellent and I would like to proceed with it.  So, I am looking for a few Associate Researchers/Writers to join me.  I am initially looking for people who can cover relatively broad swaths of the longevity sciences in depth as I have been doing.  Later, it may make sense to add more researchers/writers focusing on specialized areas.  In such a case, the initial Associates could possibly graduate to becoming Area Editors.  So I am herewith putting out a “casting call.”

CASTING CALL FOR ASSOCIATES

If you satisfy the following, please communicate with me by e-mail:

   ·        You have a passionate interest in the longevity sciences or in an applied area related to longevity, perhaps with a focus in a certain key area,

  ·        You are good at perusing the scientific literature to see what is going on,

  ·        You can express yourself well in writing and would like that writing to have targeted exposure that generates feedback,

  ·        You have sufficient training, background and patience to scan key areas of the emerging literature, identify important new trends, and generate blog entries with the sophistication and degree of literature documentation typically found in this blog.  A number of  readers have commented that this blog is the best source of scientific information related to aging on the web.  I want to keep it that way,

  ·        You are aligned with the Mission of this blog and willing to respect the blog guidelines outlined here.  The Mission of the blog is to present clearly information on key current research developments pertaining to aging and information on related technological and social topics.  Secondarily, it is to share informed opinions on the same topic.  The target audience includes professionals and students in the aging science community, health and geriatric practitioners, and informed individuals with a substantial interest in aging and aging sciences. 

  ·        You would like to get your signed writings out to a growing International community which I estimate currently to be more than 15,000 regular readers.  Currently, about 2,000 different readers visit the blog every day and new registrations from all over the world keep coming in every day.

  ·        You are willing to research and write at least one blog entry a month.  Documented mini-reviews of key topics are particularly welcome. The history of previous blog entries illustrates consider acceptable topics and blog formats, the degree of citation documentation, and the quality of the writing I will be looking for. 

  ·        You are willing to follow the general guidelines of this blog such as no commercial product promotions, no giving of medical advice and staying broadly “on topic” with respect to longevity.  While individual blog entries can be concerned with specific theories of aging or anti-aging interventions, the blog itself is inclusive of a wide variety of viewpoints provided that they are informed and anchored in respectable research.  Opinions, when offered, will be identified as such.  And I will also entertain occasional humor pieces,

  ·        You are willing to work now for the same compensation I am getting – zero pay but significant acknowledgement and opportunity to learn,

  ·        You are willing to have me review and possibly lightly edit your blog entries before they are published on the blog.  And I will reserve the right to not publish any writings if I feel they don’t meet quality or other standards of the blog.   

 My e-mail is vegiuliano@comcast.net.  Please use the e-mail heading BLOG WRITER so I can easily sort your message out from junk.  Tell me about yourself, your background, what you know/don’t know, your academic and work status, any institutional affiliation you may have or had, why you want to contribute and what you have to offer.  Also please point me to online examples of your relevant writings or attach same to your e-mails.  Finally, you might wish to identify the subject of any initial blog entries you might want to write. 

If I invite you to join me as an Associate, I will do an editorial review of your blog entries before they go online and everything you write will be attributable to your authorship.

Please do not let your age or academic or institutional status be seen as a barrier here if you have what it takes to do the job.  Whether you are a vital oldster like me or a young graduate student, this could be an opportunity to get yourself out to a big audience of readers and make a difference.

I introduced the PPPPM concept a year ago in a blog post Harnessing the engines of finance and commerce for life-extension.   I wrote that post just after having attended the 2010 version of the 2010 Bio-IT World Conference & Expo.  I speculated that PPPPM will create a basic shift that profoundly affects our health and longevity.  In that blog entry I characterized PPPPM this way: 

“1. The objective of PPPPM is not so much to cure diseases as it is to detect and predict disease susceptibilities before a disease starts or at very early stages of disease progression and initiate personalized interventions to prevent the progression of the disease before it becomes symptomatic or does damage.

 2. PPPPM is participatory in the sense that the collaborative participation of large numbers of health research institutions and care agencies is involved in doing the research and creating the infrastructure to make it workable. It involves a tight and continuing linkup loop of researchers, practitioners, patients and healthy people who want to stay healthy.

Together, these studies suggest that negative health and longevity effects could well result from the prolonged taking of large doses of glucosamine.

Efficacy of glucosamine for averting or treating osteoarthritis is another matter with some studies supporting its capability to address joint diseases and other studies suggesting that the existence of such a capability is questionable. The last study cited above suggests it may be efficacious.   Also in that category is the work reported in the March 2011 publication Effects of glucosamine derivatives and uronic acids on the production of glycosaminoglycans by human synovial cells and chondrocytes. “Glucosamine (GlcN) has been widely used to treat osteoarthritis (OA) in humans. However, its chondroprotective action on the joint is poorly understood. In this study, to elucidate the chondroprotective action of GlcN, we examined the effects of GlcN-derivatives (GlcN and N-acetyl-D-glucosamine) and uronic acids (D-glucuronic acid and D-galacturonic acid) (0.1-1 mM) on the production of glycosaminoglycans (GAG), such as hyaluronic acid (HA), keratan sulfate and sulfated GAG by human synovial cells and chondrocytes. — Together these observations indicate that GlcN may exhibit chondroprotective action on joint diseases such as OA by modulating the expression of HA-synthesizing enzymes and inducing the production of HA (a major component of GAG contained in synovial fluid) especially by synovial cells.”

By Vince Giuliano 

Minor update July 12, 2013

Pyrroloquinoline quinone (PQQ), a redox cofactor available as a dietary supplement, appears to have at least three central biological effects with powerful downstream health and longevity consequences: it stimulates the generation of PGC1-alpha, results in expression of SIRT3, and induces mitochondrial biogenesis.  After brief recapitulation of background, I review some of the key research literature involved.  Of possible practical significance, supplementation with PQQ could possibly offer the benefits of exercise in a pill.

 Background on PGC-1alpha

In a June 2010 blog entry AMPK and longevity, I discussed how exercise activates the AMPK pathway and the role of PGC-1alpha (peroxisome-proliferator-activated receptor gamma co-activator-1alpha) as a co-transcriptional regulation factor that induces mitochondrial biogenesis by activating transcription factors.

The August 2010 blog entry PGC-1alpha and exercise provides a further and more general introduction to PGC1alpha.  I said “You can probably expect to hear a lot about PGC-1alpha as time goes on because this remarkable substance is turning out to have a lot to do with health and longevity. It appears to be the mediator of the health benefits produced by exercise. This blog post is about PGC-1alpha, about its relationship to exercise, and about efforts to stimulate it with various substances, in essence seeing if it is possible to provide “exercise in a pill.” 

In that blog entry I described how exercise generates PGC1alpha. Expression of PGC-1alpha can also come about as a consequence of cellular stress such as induced by cold.  I also discussed a number of physiological properties of PGC-1alpha affecting health and longevity including:

·        PGC-1alpha regulates energy metabolism involving both white and brown fat.  “PPARgamma coactivator-1alpha (PGC-1alpha), in cooperation with several transcription factors, has emerged as a key regulator of several aspects of mammalian energy metabolism including mitochondrial biogenesis, adaptive thermogenesis in brown adipose tissue, glucose uptake, fiber type-switching in skeletal muscle, gluconeogenesis in liver and insulin secretion from pancreas. Recent studies have shown a reduced expression of PGC-1alpha in skeletal muscle of diabetic and prediabetic humans. Moreover, expression of PGC-1alpha in white fat cells activates a broad program of adaptive thermogenesis characteristic of brown fat cells(ref).”

·         “PGC-1alpha turns on the biogenesis of mitochondria primarily in brown fat, working through NRF1, NRF2 and ERRalpha. It promotes fatty acid oxidation working through the PPARs and RXRs, NRF1 and NRF2, combats ROS and promotes glucose utilization, promotes oxidative phosphorylation working via NRF2 and ERRalpha, promotes angiogenesis working through ERRalpha, and contributes to fiber-type switching.”

·        “PGC-1alpha stimulates mitochondrial biogenesis and promotes the remodeling of muscle tissue to a fiber-type composition that is metabolically more oxidative and less glycolytic in nature, and it participates in the regulation of both carbohydrate and lipid metabolism(ref).”

·        Exercise-induced expression of PGC-1alpha appears to enhance insulin sensitivity.  Thus, it is likely that maintenance of upregulated levels of PGC-1alpha is protective against diabetes.

·        Muscle PGC-1alpha protects against oxidative damage in aging muscle and PGC1alpha prevents age-related loss of endurance running capacity.

·        “It is highly likely that PGC-1alpha is intimately involved in disorders such as obesity, diabetes, and cardiomyopathy. In particular, its regulatory function in lipid metabolism makes it an inviting target for pharmacological intervention in the treatment of obesity and Type 2 diabetes(ref).”

Background on sirt3 mitochondrial biogenesis

Besides the above references to mitochondrial biogenesis, the blog entry SIRT3 research – tying together knowledge of aging points out:

·        Systematic exercise up-regulates PGC-1alpha and increases SIRT3 expression as well as associated CREB phosphorylation. “CREB (cAMP response element-binding) is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the downstream genes^[1] (ref).”

·        Cellular stress causes SIRT3 to translocate from the nucleus to the mitochondria and to be highly expressed in brown adipose tissue.  SIRT3 is a mitochondrial sirtuin protein that serves to deacetylate acetyllysine-modified proteins in mitochondria.  

·        “(PGC-1alpha) plays important roles in adaptive thermogenesis, gluconeogenesis, mitochondrial biogenesis and respiration. PGC-1alpha induces several key reactive oxygen species (ROS)-detoxifying enzymes, –Here we show that PGC-1alpha strongly stimulated mouse Sirt3 gene expression in muscle cells and hepatocytes. – Furthermore, Sirt3 was essential for PGC-1alpha-dependent induction of ROS-detoxifying enzymes and several components of the respiratory chain, including glutathione peroxidase-1, superoxide dismutase 2, ATP synthase 5c, and cytochrome c. — Our results indicate that Sirt3 functions as a downstream target gene of PGC-1alpha and mediates the PGC-1alpha effects on cellular ROS production and mitochondrial biogenesis. Thus, SIRT3 integrates cellular energy metabolism and ROS generation(ref).”

 Background on PQQ

PQQ is a quinone, a bacterial redox co-factor and antioxidant.  It is a natural dietary substance found in common foods, good sources being parsley, green tea, tofu, tomatoes green peppers, kiwi fruit and papaya(ref).The roots of the original discovery of PQQ goes back to 1964(ref) and the substance was first isolated in 1979(ref).  However, the biological significance of the substance has been discovered only through a chain of slowly-developing research.  Much of the original research on PQQ was concerned with its roles in bacteria.  PQQ was not known to be essential to human metabolism until 2003 and research on its central roles in stimulating PGC-1alpha and mitochondrial biogenesis was published until 2010.  The Wikipedia article on PQQ provides an excellent overview with an ample list of research citations. 

The basic relevance of PQQ in terms of the above discussion, put simply, is that it is an upstream activator of CREB which is an activator of PGC-1alpha which in turn activates SIRT3.  Therefore, PQQ is potentially an initiator of the chain of health and longevity benefits that devolve from expression of PGC-1alpha and SIRT3.  The substance could be the long sought-after “exercise in pill form.”

There appear to be some 200 publications on PQQ including a few books.  I will skip over the historical publications and start with a key 2010 publication and work selectively forwards from there.  That 2010 publication is Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression.  “Bioactive compounds reported to stimulate mitochondrial biogenesis are linked to many health benefits such increased longevity, improved energy utilization, and protection from reactive oxygen species. Previously studies have shown that mice and rats fed diets lacking in pyrroloquinoline quinone (PQQ) have reduced mitochondrial content. Therefore, we hypothesized that PQQ can induce mitochondrial biogenesis in mouse hepatocytes. Exposure of mouse Hepa1–6 cells to 10–30 μm PQQ for 24–48 h resulted in increased citrate synthase and cytochrome c oxidase activity, Mitotracker staining, mitochondrial DNA content, and cellular oxygen respiration. The induction of this process occurred through the activation of cAMP response element-binding protein (CREB) and peroxisome proliferator-activated receptor-gamma coactivator-alpha (PGC-1alpha), a pathway known to regulate mitochondrial biogenesis. PQQ exposure stimulated phosphorylation of CREB at serine 133, alpha mRNA and protein expression. PQQ did not stimulate mitochondrial biogenesis after small interfering RNA-mediated reduction in either PGC-1alpha or CREB expression. Consistent with activation of the PGC-1alpha pathway, PQQ increased nuclear respiratory factor activation (NRF-1 and NRF-2) and Tfam, TFB1M, and TFB2M mRNA expression. Moreover, PQQ protected cells from mitochondrial inhibition by rotenone, 3-nitropropionic acid, antimycin A, and sodium azide. The ability of PQQ to stimulate mitochondrial biogenesis accounts in part for action of this compound and suggests that PQQ may be beneficial in diseases associated with mitochondrial dysfunction.”

It is established that cAMP response element-binding protein (CREB) is an important regulator of PGC-1alpha that facilitates PGC-1alpha activation (ref).

NRF-2 is introduced in the blog entry Nrf2 and cancer chemoprevention by phytochemicals and I have mentioned its beneficial effects in a number of other blog postings.  ““Nuclear factor-erythroid-2-related factor 2 (Nrf2) plays a crucial role in the coordinated induction of those genes encoding many stress-responsive and cytoptotective enzymes and related proteins. These include NAD(P)H:quinone oxidoreductase-1, heme oxygenase-1, glutamate cysteine ligase, glutathione S-transferase, glutathione peroxidase, thioredoxin, etc.(ref).” (Several additional blog entries written after this one further characterize the health benefits of Nrf2.)

 “The function of PQQ in mammalian physiology remains controversial. PQQ has been proposed as a vitamin (19), but it has not been demonstrated that PQQ serves as an enzyme cofactor in mammalian tissues (20, 21). Upon appreciation that mitochondrial content can be influenced by PQQ nutritional status and that reported beneficial effects of PQQ may be directly related to mitochondrial function, we hypothesized that PQQ may induce mitochondrial biogenesis through a mitochondrial-related cell signaling mechanism. Given that many mitochondrial-related events are regulated by PGC-1alpha and nuclear respiratory factors (15), we hypothesized that PQQ may interact with a PGC-1alpha-related pathway. We used the mouse Hepa1–6 hepatocyte cell line as a model to investigate these hypotheses. We also explored whether PQQ may protect against the toxic effects of mitochondrial electron transport chain inhibition(ref).”

The aforementioned article goes on to describe experimental procedures that establish:

·        PQQ induces mitochondrial biogenesis.

·        PQQ induces nuclear respiratory factor (NRF) activation, both NRF-1 and NRF-2.  

·        PQQ induces PGC-1alpha promoter activation and increases PGC-1alpha mRNA and protein expression.  Further, PGC-1alpha binding can directly regulate NRF-1 and NRF-2 activity.

·        PGC-1alpha is required for the induction of mitochondrial biogenesis by PQQ.

·        PQQ stimulates the phosphorylation of CREB at serine 133 and CREB is required for PQQ-induced mitochondrial biogenesis.

·        PQQ-mediated mitochondrial biogenesis is not due to auto-oxidation or IPQ addition.  That is, “PQQ-induced mitochondrial biogenesis and nuclear respiratory factor activation is not caused by generation of either hydrogen peroxide, superoxide, or IPQ in the media by PQQ(ref).” 

·        PQQ improves cell viability and preserves mitochondrial function due to mitochondrial inhibitors.

·        The exact role of CREB in  PQQ stimulation of  PGC-1alpha is not clear. “CREB has been shown to regulate PGC-1alpha, and data shown here suggest that PQQ acts through CREB to regulate PGC-1alpha, but regulation of the PGC-1alpha and PGC-1-related co-activator by CREB has not yet been demonstrated. Also, it is recognized that the PGC-1 family of co-activators likely act and respond to differing physiological stimuli and processes (ref).”

PQQ and neuroprotectivity

 The 2011 publication The neuroprotective action of pyrroloquinoline quinone against glutamate-induced apoptosis in hippocampal neurons is mediated through the activation of PI3K/Akt pathwayreports “In this study, we investigated the effects of PQQ on glutamate-induced cell death in primary cultured hippocampal neurons and the possible underlying mechanisms. We found that glutamate-induced apoptosis in cultured hippocampal neurons was significantly attenuated by the ensuing PQQ treatment, which also inhibited the glutamate-induced increase in Ca2+ influx, caspase-3 activity, and ROS production, and reversed the glutamate-induced decrease in Bcl-2/Bax ratio. The examination of signaling pathways revealed that PQQ treatment activated the phosphorylation of Akt and suppressed the glutamate-induced phosphorylation of c-Jun N-terminal protein kinase (JNK). — Taken together, our results indicated that PQQ could protect primary cultured hippocampal neurons against glutamate-induced cell damage by scavenging ROS, reducing Ca2+ influx, and caspase-3 activity, and suggested that PQQ-activated PI3K/Akt signaling might be responsible for its neuroprotective action through modulation of glutamate-induced imbalance between Bcl-2 and Bax.”

PQQ and uranium toxicity

The 2011 publication Uranium exerts acute toxicity by binding to pyrroloquinoline quinone cofactor provides at least one explanation of why uranium is so toxic – it binds to PQQ and prevents its biological actions.  “Uranium as an environmental contaminant has been shown to be toxic to eukaryotes and prokaryotes; however, no specific mechanisms of uranium toxicity have been proposed so far. Here a combination of in vivo, in vitro, and in silico studies are presented describing direct inhibition of pyrroloquinoline quinone (PQQ)-dependent growth and metabolism by uranyl cations. Electrospray-ionization mass spectroscopy, UV-vis optical spectroscopy, competitive Ca(2+)/uranyl binding studies, relevant crystal structures, and molecular modeling unequivocally indicate the preferred binding of uranyl simultaneously to the carboxyl oxygen, pyridine nitrogen, and quinone oxygen of the PQQ molecule. The observed toxicity patterns are consistent with the biotic ligand model of acute metal toxicity. In addition to the environmental implications, this work represents the first proposed molecular mechanism of uranium toxicity in bacteria, and has relevance for uranium toxicity in many living systems.”

Other health benefits of PPQ

Here is a sample of recent publications outlining other health benefits of PPQ, particularly as related to cancers and Alzheimer’s disease:

·        Pyrroloquinoline quinone inhibits the fibrillation of amyloid proteins. (2010)

·        Role of glutathione in augmenting the anticancer activity of pyrroloquinoline quinone (PQQ)  (2010)

·        Protective effect of pyrroloquinoline quinone against Abeta-induced neurotoxicity in human neuroblastoma SH-SY5Y cells  (2009)

·        Identification of transcriptional networks responding to pyrroloquinoline quinone dietary supplementation and their influence on thioredoxin expression, and the JAK/STAT and MAPK pathways  (2010)

·        The inhibitory effect of pyrroloquinoline quinone on the amyloid formation and cytotoxicity of truncated alpha-synuclein (2010)

In addition, there have been many recent studies concerned with the chemistry and biochemistry of PQQ and its behavior in a number of bacteria.

The case for PQQ as a dietary supplement

 The first-mentioned publication goes on in its discussion to make what seems to be a possible case for PQQ supplementation: “The induction of mitochondrial biogenesis by PQQ has a number of health implications. PGC-1α elevation, particularly in muscle and adipose tissue, may also be helpful in that PGC-1alpha expression is decreased in obesity (56, 57). CREB null and PGC-1alpha null mice have hepatic steatosis and impaired gluconeogenesis and β-oxidation (38, 58, 59). PQQ-deficient mice have elevated serum triglycerides, which is reversed upon PQQ repletion (1). In addition, mice with deletion of all CREB isoforms have reduced commissural structure formation and impaired fetal T cell development (60), and other mouse models of CREB-targeted deletion show impaired memory and neurodegeneration (61, 62). Likewise, dietary PQQ deprivation results in immune dysfunction (63). PQQ is also neuroprotective when administered by intraperitoneal injection (64, 65) or diet supplementation (66).”

PQQ is not the only dietary supplement that can activate PGC-1alpha and therefore unleash its chain of beneficial results including enhanced SIRT3 expression and mitochondrial biogenesis.  Resveratrol and and other substances in my anti-aging firewalls dietary supplement regimen, can also do this.  And the drug rapamycin can also enhance PGC-1alpha expression(ref).

The basic arguments for PQQ supplementation relate to solubility and bioavailability.  Going on to quote additionally from the 2010 publication: “Although other phytochemicals are associated with the activation of cell signaling pathways important to mitochondrial function, PQQ has properties that set it apart from other compounds. As an example, resveratrol and genisten have been demonstrated to affect cell-signaling pathways, including those important for mitochondrial biogenesis. Resveratrol can induce deacetylation of PGC-1alpha (ref) and AMP-activated protein kinase activation (ref), which are potential mechanisms for PGC-1α activation. Both resveratrol and genistein are relatively insoluble in water, and increasing its water solubility does not increase resveratrol absorption (ref), although genistein bioavailability can be increased by complexing genistein with cyclodextrins (ref). In contrast, PQQ is relatively water-soluble (>1 g of PQQ/liter of water) and is easily absorbed at low dietary concentrations intakes (ref). Although genistein can induce PGC-1alpha protein expression and mitochondrial biogenesis (3), genistein may also have phytoestrogenic properties because of its ability to activate the estrogen receptor (ref).”

Going on: “The observed effects of PQQ are also observed at concentrations lower than those for resveratrol and genistein, particularly in vivo. In cell cultures in vitro, PQQ causes changes in mitochondriogenesis and function at concentrations similar to those reported recently for small molecule activators of SIRT1 (ref), which are being explored for their therapeutic potential (ref). These observations suggest that further study related to PQQ is warranted. One important note is that PQQ can increase PGC-11alpha mRNA transcription, which is different from the post-translation regulation of PGC-1alpha by resveratrol and raises the likelihood that a combination of various compounds, such as are often present in fruits and vegetables, can stimulate mitochondrial biogenesis through different modes of action. Because mitochondria function as the principal energy source of the cell, compromised function of this key organelle is linked to numerous diseases and metabolic disorders (ref)(ref). In this regard, PQQ would appear to have therapeutic potential similar to resveratrol, genistein, hydroxytyrosol, quercetin, or other compounds that can induce mitochondrial biogenesis(ref).”

Does PGG supplementation make sense?

My impression is that the PQQ supplementation phenomenon is new and just taking off. A few of the supplement companies have picked up on the 2010 findings outlined above and are starting to offer PQQ supplements, Life Extension Foundation having been a leader in this regard.  Most supplement vendors offer PQQ only in proprietary combinations with other substances.   I have found this discussion of PPG supplementation dosage on a site providing practical Pyrroloquinoline Quinone & Methoxatin information. My impression is that the information on that site is responsible and informative although not completely documented.  For example, that site contains an  interesting table for the PQQ  content that researchers have found in food.  That discussion points out that there are many imponderable factors that could affect what is the optimum amount for a healthy adult to take as a daily PQQ supplement. “This question has not been fully resolved and is complicated by the inability to measure all forms of PQQ (pyrroloquinoline quinone | methoxatin). However, it is possible to make several good inferences from current animal studies and data–.”  The discussion argues that, all things considered, 10-20mg of PQQ a day is probably a reasonable dose.  The supplement-makers apparently concur and the PQQ supplement products I have seen range from having 5 to 20 mg of PQQ per pill. 

In considering PQQ supplementation, I hasten to point out that a number of other dietary supplements offer positive benefits for mitochondrial health including r-alpha-lipoic acid, acetyl-l-carnitine, resveratrol, quercetin and co-enzyme Q10.  For a discussion of the supplements I have been  taking related to mitochondrial health, you can have a look at the Mitochondrial Damage Firewall in my treatise.

Some supplement marketers are representing PQQ as being a new vitamin, although whether it satisfies the criteria for being a vitamin has been disputed(ref).

Given that I exercise at least 45 minutes a day, eat a reasonable diet, and take all the supplements in my anti-aging firewalls dietary supplement regimen, do I think additional enhancement of PGC-1alpha and all of the associated health benefits would come about for me if I added PQQ as a supplement?  Or would adding PQQ to my dietary regimen be simply redundant?  Or could I increase the effectiveness or reduce the cost of the regimen by substituting PQQ for other supplements?  I simply did not know when I first drafted this blog in April 2011.  Because of the importance of SIRT3 expression, however, in 2012 I started regular supplementation with PQQ and have continued that pattern since (July 2013).

Since drafting the above over two years ago,  another 50 research publications relating to PQQ have appeared in pubmed.org, further elucidating its mechanisms of action and health benefits. In the interim I have developed an increased appreciation of the importance of SIRT3 expression for controlling mitochondrial ROS and general health maintenance during aging.  At some point I will generate a new blog entry covering the new research and updating this one.

The situation at the Fukushima nuclear plant in Japan is giving great urgency to the issue of personal protection against ionizing radiation.  This blog entry is about how a degree of personal protection against radiation damage can be achieved by taking antioxidants.  I do not think it is an exaggeration to say that what I will be discussing could in the long term save the lives of millions of people. 

The Fukushima nuclear disaster

As of this writing the situation at the Fukushima Daiichi reactors remains uncontrolled.   It is a slowly-unfolding disaster, appearing to get worse and worse.   Smoke or metallic vapor from overheated or melted fuel rods contain large quantities of radioactive fission byproducts.   And very little can be done to stop fuel rod overheating without pumping in large quantities of water which releases radioactive pollution into the environment via steam and water runoff.  An immense amount of radioactive material has already been released into the atmosphere affecting a vast area of Japan as well as the ocean.   Many workers at the plant are expected to die quickly due to radiation exposure.  We don’t know how and when the continuing release of radiation can be contained.  Much of Japan including Tokyo could be contaminated semi-permanently by fallout resulting in radiation levels orders of magnitude higher than are normally acceptable.  Tens of millions of people are likely to be effected. 

An excellent source of information on the situation in Japan is the blog All Things Nuclear.  The March 30 entry relates: “Today the IAEA has finally confirmed what some analysts have suspected for days: that the concentration per area of long-lived cesium-137 (Cs-137) is extremely high as far as tens of kilometers from the release site at Fukushima Dai-Ichi, and in fact would trigger compulsory evacuation under IAEA guidelines. — The IAEA is reporting that measured soil concentrations of Cs-137 as far away as Iitate Village, 40 kilometers northwest of Fukushima-Dai-Ichi, correspond to deposition levels of up to 3.7 megabecquerels per square meter (MBq/sq. m). This is far higher than previous IAEA reports of values of Cs-137 deposition, and comparable to the total beta-gamma measurements reported previously by IAEA and mentioned on this blog. — This should be compared with the deposition level that triggered compulsory relocation in the aftermath of the Chernobyl accident: the level set in 1990 by the Soviet Union was 1.48 MBq/sq. m.  — Thus, it is now abundantly clear that Japanese authorities were negligent in restricting the emergency evacuation zone to only 20 kilometers from the release site.”  Other blog entries refer to the release of substantial quantities of radioactive iodine-131 and to how plutonium is being found in soil samples.

Background on nuclear radiation

For the general Japanese public, the biggest concern is not direct radiation from the Fukushima plant but rather radioactive substances which are released into the environment either via the atmosphere or via runoff into the ocean.  Radioactive substances can enter the body via the air, groundwater, tap water or foods or vegetables consumed. Three radioactive substances of primary concern are:

Radio iodine-131:  Although having a half life of only 8 days, iodine-131 can be dangerous if ingested by someone with a thyroid iodine deficiency.  It is a beta radiation emitter, which means the radiation is not a threat unless the emitting substance is inside the body. “Due to its mode of beta decay, iodine-131 is notable for causing mutation and death in cells which it penetrates, and other cells up to several millimeters away. For this reason, high doses of the isotope are sometimes paradoxically less dangerous than low doses, since they tend to kill thyroid tissues which would otherwise become cancerous as a result of the radiation. For example, children treated with moderate dose of I-131 for thyroid adenomas had a detectable increase in thyroid cancer, but children treated with a much higher dose did not(ref).”  As long as the damaged Fukushima plant continues to release iodine-131 into the environment, it will be a threat. 

Caesium-137: Has a half life of about 30 years and emits beta and gamma radiation.  Because it is chemically similar to potassium, it is readily absorbed in vegetables and human bodies.  “Caesium-137 is water-soluble, and the biological behavior of caesium is similar to that of potassium and rubidium. After entering the body, caesium gets more or less uniformly distributed throughout the body, with higher concentration in muscle tissues and lower in bones. The biological half-life of caesium is rather short at about 70 days.^[6] Experiments with dogs showed that a single dose of 3800 μCi/kg (approx. 44 μg/kg of caesium-137) is lethal within three weeks^[7](ref).”

Plutonium:  Plutonium is a byproduct of nuclear reactions, is the heaviest stable element and has been called ‘the most toxic substance known to man,” emitting alpha, beta and gamma radiation.  The most important isotope of plutonium is plutonium-239, with a half-life of 24,100 years..  Plutonium-238 has a half-life of 88 years and emits alpha particles. plutonium-244 has a half-life of about 80 million years. “Isotopes and compounds of plutonium are radioactive poisons that accumulate in bone marrow. Contamination by plutonium oxide (spontaneously oxidized plutonium) has resulted from a number of nuclear disasters and radioactive incidents including military nuclear accidents where nuclear weapons have burned.^[86] Studies of the effects of these smaller releases, as well as of the widespread radiation poisoning sickness and death following the Atomic bombings of Hiroshima and Nagasaki, have provided considerable information regarding the dangers, symptoms and prognosis of radioactive poisoning. PMID 19454804(ref).”

As reported in the news, higher than normal levels of both iodine-131 and caesium-137 have been noted not only in Japan but worldwide due to the Fukushima incident.  And plutonium has been found in soil samples near the reactor sites.

According to the International Atomic Energy Agency Briefing on Fukushima Nuclear Accident, 31 March 2011 (14:00 UTC), On 30 March, deposition of iodine-131 was detected in 8 prefectures, and deposition of cesium-137 in 12 prefectures. On 30 March in the prefectures where deposition of iodine-131 was reported, the range was from 2.5 to 240 becquerel per square metre. For caesium-137, the range was from 3 to 57 becquerel per square metre. In the Shinjyuku district of Tokyo, the daily deposition of both iodine-131 and cesium-137 on 30 March was below 30 becquerel per square metre. — Since our briefing of yesterday, significant data related to food contamination has been submitted by the Japanese Ministry of Health, Labour and Welfare. Seventy-six samples were taken from 28-30 March, and reported on 30 March. Analytical results for 51 of the 76 samples for various vegetables, fruit (strawberry), seafood (sardines), and unprocessed raw milk in eight prefectures (Chiba, Fukushima, Gunma, Ibaraki, Kanagawa, Niigata, Saitama, and Yamagata), indicated that iodine-131, caesium-134 and caesium-137 were either not detected or were below the regulation values set by the Japanese authorities. However, it was reported that analytical results in Fukushima prefecture for the remaining 25 of the 76 samples for broccoli, cabbage, rapeseed, spinach and other leafy vegetables, indicated that iodine-131 and/or caesium-134 and caesium-137 exceeded the regulation values set by the Japanese authorities.”

Right now, as reported in the news, the biggest dangers from iodine-131 and caesium-137 due to the Fukushima situation are within a 100 kilometer distance of the power plant site, although levels significantly higher than normal have been reported elsewhere in Japan. Higher levels of these substances due to the Fukushima situation have also been observed in the US, both on the West and East coasts.  These US levels are so-far significantly below those considered to offer health risks.  As the damaged reactors and stored fuel rods continue to release large quantities of the radioactive substances, and because major new releases due to possible meltdowns could occur, however, the danger exists that the relatively comfortable situation in the US could change. And there is the danger of consuming contaminated vegetables or seafood anywhere it may be shipped to.   

Biological impact from radiation damage due to ingested substances is different than radiation from sources outside the body in several important respects including:  1.  Alpha and beta radiation is very short range so is of no threat when coming from substances outside the body unless those substances are touched, inhaled, eaten or otherwise penetrate the body and 2.  Radiation from a substance like iodine-131 or caesium-137 that is absorbed in body tissues continues to create damage as long as that substance is within the body.

Consequences of radiation damage

Radiation damage can be short term or long term and is measured by exposure.  Radiation dosages are measured in sieverts.  “The sievert (symbol: Sv) is the SI derived unit of dose equivalent radiation. It attempts to quantitatively evaluate the biological effects of ionizing radiation as opposed to the physical aspects, which are characterised by the absorbed dose, measured in gray. It is named after Rolf Sievert, a Swedish medical physicist renowned for work on radiation dosage measurement and research into the biological effects of radiation(ref).”

This link contains a table relating exposure in sieverts to biological impacts.  “Annual limit on intake (ALI) is the derived limit for the amount of radioactive material taken into the body of an adult worker by inhalation or ingestion in a year. ALI is the intake of a given radionuclide in a year that would result in:

• a committed effective dose equivalent of 0.05 Sv (5 rems) for a “reference human body”, or
• a committed dose equivalent of 0.5 Sv (50 rems) to any individual organ or tissue,

whatever dose is the smaller^[8](ref).”  The average natural radiation dose is 2.4 mSv per year, with a “typical range” reaching up to 10 mSv.  As the table shows, a short-term dose of as little as 2 sieverts can lead to severe medical problems and a 5-50% chance of death even with medical care.  And any dose of over 8 sieverts is sure to lead to rapid death.

The CDC has prepared a fact sheet Acute Radiation Syndrome (ARS): A Fact Sheet for the Public. 

Longer-term exposure to even low intensities of radiation can lead to mutations of cell-cycle genes and cancers

Protective measures

Known protective measures can be taken when ingestion of one of the mentioned substances is unavoidable or has already happened.  These are time-honored approaches known for decades.  Specifically:

Potassium iodide for iodine-131

Absorption of iodine-131 can be significantly reduced or avoided by taking potassium iodide, though taking such pills after exposure to iodine-131 may be useless.  A recent article in Pharmacy Practice News reports “As alarmed residents visit various Internet sites to purchase what is touted as a panacea for radiation sickness, costs of KI have skyrocketed. According to some reports, a package of 14 tablets that normally costs about $10 has soared to $540 in some ebay.com listings—a shocking 5,300% increase. Although some manufacturers are struggling to meet demands for KI in this suddenly lucrative market, others have simply given up, temporarily ceasing production.^1-4”  And this increase is in the US, not Japan.  Further, the article reports “In situations where internal radiation contamination is suspected, the initial concern is inhalation of radioactive iodine, which is readily absorbed by the thyroid gland, leading to thyroid injury/cancer, particularly in infants/fetus, children and patients with low iodine stores. KI is known to flood the thyroid gland with stable iodine, preventing the organ from absorbing radioactive iodine—but it can only go so far. Consumers should be told that KI only protects the thyroid (not other parts of the body) from radioactive iodine—it cannot reverse effects of radioactive iodine once damage to the thyroid has occurred—and it cannot protect the body from radioactive elements other than radioactive iodine.5 — A dose of KI is recommended before or immediately following radiation exposure in all children and adults under the age of 40 years who are not allergic to iodine or shellfish, and if radiation still poses a threat 24 hours later, a repeat dose is administered (unless the patient is pregnant or breastfeeding, or a newborn infant).”  Use of potassium iodide in other than emergency situations is definitely not recommended.  You can see the document Prophylactic Use of Potassium Iodide (KI) in Radiological Emergencies – Information for Physicians. 

Chelating Plutonium via DPTA

The 2005 publication Chelating agents used for plutonium and uranium removal in radiation emergency medicine points to an approach for removal of ingested plutonium.  A chelating agent is one that chemically grabs molecules of an offending substance for transportation outside of the body.  DPTA is a chelating agent that is approved by the FDA for removal of plutonium as well as americium, and curium which are also radioactive.  The CDC document Facts About DTPA provides some basic information about the substance including: “DTPA is a kind of medicine called a chelating agent. Chelating agents work by binding and holding on to radioactive materials or poisons that get into the body. Once bound to a radioactive material or poison, the chelating agent is then passed from the body in the urine. Chelating agents help decrease the amount of time it takes to get a poison out of the body. — What does DTPA do?  When radioactive materials get into the body through breathing, eating, drinking, or through open wounds, we say that “internal contamination” has occurred. Over the past 50 years, almost all cases of internal contamination have happened in people who use radioactive materials in their work. Since the 1960s, doctors have used DTPA as a chelating agent to treat internal contamination from radioactive materials such as americium, plutonium, californium, curium, and berkelium. Currently, DTPA is approved by the U.S. Food and Drug Administration (FDA) for chelation of only three radioactive materials: plutonium, americium, and curium. — What DTPA cannot do: Knowing what DTPA cannot do is also important. DTPA cannot bind all of the radioactive materials that might get into a person’s body after a radiological or nuclear event, such as a terrorist attack with a “dirty bomb.” This medicine cannot prevent radioactive materials from entering the body. DTPA cannot reverse the health effects caused by radioactive materials once these materials have entered the body. — How does DTPA work?  DTPA comes in two forms: calcium (Ca-DTPA) and zinc (Zn-DTPA). Both forms work by tightly chelating (holding on to) plutonium, americium, and curium. These radioactive materials (bound to DTPA) are then passed from the body in the urine. When given within the first day after internal contamination has occurred, Ca-DTPA is about 10 times more effective than Zn-DTPA at chelating plutonium, americium, and curium. After 24 hours have passed, Ca-DTPA and Zn-DTPA are equally effective in chelating these radioactive materials. — How well does DTPA work?  Chelating agents work best when given shortly after radioactive materials or poisons have entered the body. The more quickly a radioactive material or poison is removed from the body, the fewer and less serious the health effects will be. After 24 hours, plutonium, americium, and curium are harder to chelate. However, DTPA can still work to remove these radioactive materials from the body several days or even weeks after a person has been internally contaminated. — Who should get DTPA? Many people could be internally contaminated after a radiological or nuclear terrorist event. People contaminated with small amounts of radioactive materials might not need treatment with DTPA. Doctors and public health authorities will work together to decide who will likely benefit from DTPA treatment.”  The literature related to plutonium chelation tends to be old with some articles going back 50 years or more(ref).

Clearing Caesium-137 with Prussian Blue

The CDC fact sheet Prussian blue tells the story: “Prussian blue can remove certain radioactive materials from people’s bodies, but must be taken under the guidance of a doctor. — People may become internally contaminated (inside their bodies) with radioactive materials by accidentally ingesting (eating or drinking) or inhaling (breathing) them, or through direct contact (open wounds). The sooner these materials are removed from the body, the fewer and less severe the health effects of the contamination will be. Prussian blue is a substance that can help remove certain radioactive materials from people’s bodies. However, small amounts of contamination may not require treatment. Doctors can prescribe Prussian blue if they determine that a person who is internally contaminated would benefit from treatment. — What Prussian blue is:  Prussian blue was first produced as a blue dye in 1704 and has been used by artists and manufacturers ever since. It got its name from its use as a dye for Prussian military uniforms. Prussian blue dye and paint are still available today from art supply stores. — People SHOULD NOT take Prussian blue artist’s dye in an attempt to treat themselves. This type of Prussian blue is not designed to treat radioactive contamination and is not made for that purpose. People who are concerned about the possibility of being contaminated with radioactive materials should go to their doctors for advice and treatment.  — Use of Prussian blue to treat radioactive contamination: Since the 1960s, Prussian blue has been used to treat people who have been internally contaminated with radioactive cesium (mainly Cs-137) and nonradioactive thallium (once an ingredient in rat poisons). Doctors can prescribe Prussian blue at any point after they have determined that a person who is internally contaminated would benefit from treatment. Prussian blue will help speed up the removal of cesium and thallium from the body. —How Prussian blue works: Prussian blue traps radioactive cesium and thallium (mainly Tl-201) in the intestines and keeps them from being re-absorbed by the body. The radioactive materials then move through the intestines and are excreted (passed) in bowel movements. Prussian blue reduces the biological half-life1 of cesium from about 110 days to about 30 days. Prussian blue reduces the biological half-life of thallium from about 8 days to about 3 days. Because Prussian blue reduces the time that radioactive cesium and thallium stay in the body, it helps limit the amount of time the body is exposed to radiation. — Who can take Prussian blue/ The drug is safe for most adults, including pregnant women, and children (2 ─12 years). Dosing for infants (ages 0 ─2 years) has not been determined yet. Women who are breast feeding their babies should stop breast feeding if they think they are contaminated with radioactive materials and consult with their doctors. People who have had constipation, blockages in the intestines, or certain stomach problems should be sure to tell their doctors before taking Prussian blue. Before taking Prussian blue, people also should be sure to tell their doctors about any other medicine they are taking. — How Prussian blue is given:  Prussian blue is given in 500-milligram capsules that can be swallowed whole. People who cannot swallow pills can take Prussian blue by breaking the capsules and mixing the contents in food or liquid. Breaking open the capsules will cause people’s mouths and teeth to be blue during the time of treatment. — The dose of Prussian blue depends on the person’s age and the amount of contamination in the body. Prussian blue usually is given 3 times a day for a minimum of 30 days, depending on the extent of the contamination. – Warning:  People SHOULD NOT take Prussian blue artist’s dye in an attempt to treat themselves. This type of Prussian blue is not designed to treat radioactive contamination and is not made for that purpose. People who are concerned about the possibility of being contaminated with radioactive materials should go to their doctors for advice and treatment.”

Taking antioxidants to minimize radiation damage

The above treatments are directed to elimination of dangerous radioactive substances from the body and may constitute a first level of defense in case of ingestion of radioactive substances through breathing, eating, drinking or exposure of open wounds.  As recommended by the CDC they should be undertaken only under the guidance of a physician.  Even using these approaches, however, the various radioactive substances will be resident in the body for a certain period and can possibly create serious damage depending on exposure dose and how quickly the removal action is initiated.  There is a second level and complimentary of defense possible, and that is to minimize the damaging biological impact of radiation through taking a regimen of antioxidants.

I have written about the use of antioxidants to protect against the negative effects of medical imaging radiation first in a 2008 position paper Protection Against Radiation – The Second Line of Defense, and also briefly in an August 2009 blog entry Medical radiation risk – you can do something about it.  Medical imaging radiation usually originates from outside the body and is electromagnetic in nature making it akin to gamma radiation such as is generated by an X-ray machine or as exists in outer space.  Many studies have shown that antioxidants can be protective against biological damage caused by such exterior-originated radiation.  Many such studies are cited in my position paper and a few new ones are cited here below.  Much of this work has been sponsored by NASA and has been concerned with safety in space of astronauts. 

Would antioxidants also provide protection from in-body radiation sources such as iodine-131 or caesium-137?  The mechanisms of radiation damage are the same.  Ionizing radiation, whatever the source may be, knocks electrons loose from molecules producing free radicals.  These free radicals can propagate producing secondary showers of free radicals, particularly when generated by high-energy photons from gamma radiation.  Free radicals can generate multiple forms of damage including to tissue structures, body cell DNA, germ-line DNA and mitochondrial DNA.  From my treatise on radiation and antioxidants: “Ionizing x-radiation in any quantities is potentially deleterious to health. Radiation ionizes oxygen to produce Reactive Oxygen Species (ROS) like OH which steal electrons from lipids in cell membranes, a process called lipid peroxidation. A chain of damaging events can be let loose from a single high-energy electron event as unstable fatty acid radicals propagating in tissues produce other unstable radicals. The result can be damage to DNA or mitochondrial DNA, mangled chromosomes, protein cross-linking, cell apoptosis, genetic mutations, mutated germ cells and other forms of cell havoc. Radiation damage can show up in many ways including skin erythema, hair loss, vascular damage, internal bleeding, cataracts, cancers, weakened immune systems, sterility, mutations in offspring, premature ageing and death. Cell DNA repair mechanisms are effective in correcting some radiation-induced damage but may themselves be compromised by radiation.”

Newer literature references re antioxidants for radiation protection

My treatise PROTECTION AGAINST RADIATION – – THE SECOND LINE OF DEFENSE, last updated in 2008, provides a thorough discussion of how antioxidants are radioprotective and cites 30 of some 110 applicable literature citations I came across up to that point. Also you can check on the 2008 publication Antioxidants Reduce Consequences of Radiation Exposure.  The following are selected updates on relevant research as reported in Science Daily articles.

A March 2011 Science Daily story Antioxidant Formula Prior to Radiation Exposure May Prevent DNA Injury, Trial Suggests reports: “A unique formulation of antioxidants taken orally before imaging with ionizing radiation minimizes cell damage, noted researchers at the Society of Interventional Radiology’s 36th Annual Scientific Meeting in Chicago, Ill. In what the researchers say is the first clinical trial of its kind, as much as a 50 percent reduction in DNA injury was observed after administering the formula prior to CT scans. — People are 70 percent water, and X-rays collide with water molecules to produce free radicals (groups of atoms with an unpaired number of electrons that are dangerous when they react with cellular components, causing damage and even cell death) that can go on to do damage by direct ionization of DNA and other cellular targets, noted Murphy. The research team evaluated whether a special combination of antioxidants have an ability to neutralize these free radicals before they can do damage. — “Our intent was to develop an effective proprietary formula of antioxidants to be taken orally prior to exposure that can protect a patient’s DNA against free radical mediated radiation injury, and we have applied to patent this formulation and a specific dose strategy,” said Murphy. — The experiments measured DNA damage as a surrogate marker for DNA injury.”

A September 2008 Science Daily story Plant Antioxidant May Protect Against Radiation Exposure reports on research specifically concerned with identifying protective measures in case of a nuclear emergency: “Resveratrol, the natural antioxidant commonly found in red wine and many plants, may offer protection against radiation exposure, according to a study by the University of Pittsburgh School of Medicine. When altered with acetyl, resveratrol administered before radiation exposure proved to protect cells from radiation in mouse models.”  — The study, led by Joel Greenberger, M.D., professor and chairman of the Department of Radiation Oncology at the University of Pittsburgh School of Medicine, is overseen by Pitt’s Center for Medical Countermeasures Against Radiation. The center is dedicated to identifying and developing small molecule radiation protectors and mitigators that easily can be accessed and administered in the event of a large-scale radiological or nuclear emergency. — “New, small molecules with radioprotective capacity will be required for treatment in case of radiation spills or even as countermeasures against radiological terrorism,” said Dr. Greenberger. “Small molecules which can be easily stored, transported and administered are optimal for this, and so far acetylated resveratrol fits these requirements well.” — “Currently there are no drugs on the market that protect against or counteract radiation exposure,” he added. “Our goal is to develop treatments for the general population that are effective and non-toxic. — Dr. Greenberger and his team are conducting further studies to determine whether acetylated resveratrol eventually can be translated into clinical use as a radioprotective agent. In 2004, this same team of researchers identified the drug JP4-039, which can be delivered directly to the mitochondria, the energy producing areas of cells. When this occurs, the drug assists the mitochondria in combating radiation-induced cell death. — The results of the research were presented during the American Society for Therapeutic Radiology and Oncology’s (ASTRO) 50th Annual Meeting in Boston.”

An October 2008 2009 story Herbal Tonic For Radiotherapy? Gingko Biloba Tree May Protect Cells From Radiation Damage reports on radioprotection provided by Gingko biloba against gamma radiation from caesium-137: ” Antioxidant extracts of the leaves of the Gingko biloba tree may protect cells from radiation damage, according to a study published in the International Journal of Low Radiation. — Chang-Mo Kang of the Korea Institute of Radiological and Medical Sciences in Taegu and colleagues are interested in the protective effects of well-known herbal remedies of which Gingko biloba is one. G. biloba is a unique tree species with no close living relatives and extracts of its leaves contain antioxidant compounds including glycosides and terpenoids known as ginkgolides and bilobalides. — These compounds are thought to protect cells from damage by free radicals and other reactive oxidizing species found in the body. These are generated continuously by the body’s normal metabolism, and in excess in some diseases or after exposure to pollution or radiation. They damage proteins, DNA and other biomolecules and left unchecked can kill cells. — As such, extracts of certain plants that contain antioxidants, including G. biloba, have attracted interest for their pharmacological activity. G. biloba is currently sold as a herbal supplement and there are numerous claims for health benefits, including the possibility of preventing the onset of dementia or Alzheimer’s disease. — Kang and colleagues have now collected human white blood cells, lymphocytes, from healthy donors aged 18 to 50 years. They treated half of these cells with commercially available G. biloba extract in the laboratory and doused the other half with salt solution as an experimental control. They then compared the effects of gamma radiation from radioactive cesium on the white blood cells compared to the untreated control samples. — The team uses a light microscope to look for lymphocytes undergoing programmed cell death, or apoptosis, as a result of radiation exposure. They found that there was a significant increase in apoptosis in the untreated cells compared with those treated with G. biloba extract. Almost a third of the untreated cells underwent apoptosis compared with approximately one in twenty of the treated cells. Parallel studies with laboratory mice also demonstrated a similar protective effect against radiation poisoning. — The results suggest that the extracts can neutralize the free-radicals and oxidizing agents produced in the cells by the radiation and so prevent them from undergoing apoptosis.”

The July 2009 Science Daily story New Pill May Prevent Injury After Radiation Exposure reports “Researchers from Boston University School of Medicine (BUSM) and collaborators have discovered and analyzed several new compounds, collectively called the ”EUK-400 series,” which could someday be used to prevent radiation-induced injuries to kidneys, lungs, skin, intestinal tract and brains of radiological terrorism victims. The findings, which appear in the June issue of the Journal of Biological Inorganic Chemistry, describe new agents which can be given orally in pill form, which would more expedient in an emergency situation. — These agents are novel synthetic “antioxidants” that protect tissues against the kind of damage caused by agents such as “free radicals.” Free radicals, and similar toxic byproducts formed in the body, are implicated in many different types of tissue injury, including those caused by radiation exposure. Often, this kind of injury occurs months to years after radiation exposure. The BUSM researchers and their colleagues are developing agents that prevent injury even when given after the radiation exposure. — This paper describes a newer class of compounds, the ”EUK-400 series,” that are designed to be given as a pill. According to the researchers, experiments described in their paper prove that these agents are orally active. They also show that the new agents have several desirable “antioxidant” activities, and protect cells in a “cell death” model. — These same BUSM researchers and collaborators had previously discovered novel synthetic antioxidants that effectively mitigate radiation injuries, but had to be given by injection. “We have developed some of these agents and have studied them for over 15 years beginning with our work at the local biotechnology company Eukarion,” said senior author Susan Doctrow, PhD, a research associate professor of medicine at BUSM’s Pulmonary Center. “These injectible antioxidants are very effective, but there has also been a desire to have agents that can be given orally. A pill would be more feasible than an injection to treat large numbers of people in an emergency scenario,” she adds.”

The 2007 article Antioxidants Could Provide All-Purpose Radiation Protection reports “Two common dietary molecules found in legumes and bran could protect DNA from the harmful effects of radiation, researchers from the University of Maryland report. Inositol and inositol hexaphosphate (IP6) protected both human skin cells and a skin cancer-prone mouse from exposure to ultraviolet B (UVB) radiation, the damaging radiation found in sunlight, the team reported November 5 at the American Association for Cancer Research Centennial Conference on Translational Cancer Medicine. — According to the researchers, inositol and IP6 could decrease the severity of side effects from radiation therapy, saving healthy cells while simultaneously increasing the potency of the treatment against cancer cells. Both molecules are potent antioxidants, the Maryland researchers say, capable of preventing reactive molecules from injuring DNA and turning cells cancerous. — “Both of these potent antioxidants have been shown to have broad-spectrum anti-tumor capabilities, and now our studies confirm the degree to which these molecules protect against the DNA-damaging effects of ionizing radiation,” said Abulkalam M. Shamsuddin, M.D., professor of pathology at the University of Maryland School of Medicine. “Radiation damage is radiation damage, regardless of the source, so there could also be a protective role for IP6 in any form of radiation exposure, whether it is from a therapeutic dose or from solar, cosmic or nuclear sources.” – Normally, cells permanently damaged by radiation undergo a genetically programmed process of cell suicide, called apoptosis. Shamsuddin reports that UVB-irradiated human keratinocytes, when treated with IP6, were more likely to survive. Untreated skin cells were more likely to undergo apoptosis, indicating that the DNA in those cells was damaged irreparably and fatally. According to Shamsuddin, the treated cells take an extended pause at the point in the cellular life cycle where innate mechanisms repair DNA before the cell divides. — “IP6 certainly has some interactivity with DNA, but how exactly it works to repair DNA is still something of a mystery. There are reports that IP6 binds with DNA repair molecule Ku to bring about the repair process,” Shamsuddin said. — According to Shamsuddin, IP6 could also offer protection against accidents or purposeful incidents involving nuclear material. “It could also be advisable to use IP6 plus inositol as a cautionary treatment following a nuclear disaster or dirty bomb,” Shamsuddin said.”

Drugs under development that mitigate radiation damage

The April 2009 story Developmental Drug Helps Protect Against Radiation Damage reports “The study, led by Joel Greenberger, M.D., professor and chairman of the Department of Radiation Oncology at Pitt, is overseen by Pitt’s Center for Medical Countermeasures Against Radiation. The center is dedicated to identifying and developing small molecule radiation protectors and mitigators that can be easily accessed and administered in the event of a large-scale radiological or nuclear emergency. — JP4-039 assists the mitochondria, the energy generator of all cells, in combating irradiation-induced cell death. For this study, cells treated immediately after irradiation with JP4-039 demonstrated significant radioprotection, suggesting a potential role for the drug as a mitigator of radiation damage. — “Currently, no drugs on the market counteract the effects of radiation exposure,” said Dr. Greenberger. “We know this drug can counteract the damage caused by irradiation, and now we want to develop the ideal dosage, one that is effective for the general population while remaining non-toxic. Our goal is to take this drug through a phase I clinical trial and, once the dosage is established, develop the drug for late-stage clinical trials and market licensing.” —  The study, led by Joel Greenberger, M.D., professor and chairman of the Department of Radiation Oncology at Pitt, is overseen by Pitt’s Center for Medical Countermeasures Against Radiation. The center is dedicated to identifying and developing small molecule radiation protectors and mitigators that can be easily accessed and administered in the event of a large-scale radiological or nuclear emergency. — JP4-039 assists the mitochondria, the energy generator of all cells, in combating irradiation-induced cell death. For this study, cells treated immediately after irradiation with JP4-039 demonstrated significant radioprotection, suggesting a potential role for the drug as a mitigator of radiation damage. — “Currently, no drugs on the market counteract the effects of radiation exposure,” said Dr. Greenberger. “We know this drug can counteract the damage caused by irradiation, and now we want to develop the ideal dosage, one that is effective for the general population while remaining non-toxic. Our goal is to take this drug through a phase I clinical trial and, once the dosage is established, develop the drug for late-stage clinical trials and market licensing.”

The 2008 story Could a Nanotube-Based Drug Prevent Radiation Injury? reports “The Department of Defense has commissioned a nine-month study from Rice University chemists and scientists in the Texas Medical Center to determine whether a new drug based on carbon nanotubes can help prevent people from dying of acute radiation injury following radiation exposure. The new study was commissioned after preliminary tests found the drug was greater than 5,000 times more effective at reducing the effects of acute radiation injury than the most effective drugs currently available. — “More than half of those who suffer acute radiation injury die within 30 days, not from the initial radioactive particles themselves but from the devastation they cause in the immune system, the gastrointestinal tract and other parts of the body,” said James Tour, Rice’s Chao Professor of Chemistry, director of Rice’s Carbon Nanotechnology Laboratory (CNL) and principal investigator on the grant. “Ideally, we’d like to develop a drug that can be administered within 12 hours of exposure and prevent deaths from what are currently fatal exposure doses of ionizing radiation.” — The drug is based on single-walled carbon nanotubes, hollow cylinders of pure carbon that are about as wide as a strand of DNA. To form NTH, Rice scientists coat nanotubes with two common food preservatives — the antioxidant compounds butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) — and derivatives of those compounds. — “The same properties that make BHA and BHT good food preservatives, namely their ability to scavenge free radicals, also make them good candidates for mitigating the biological affects that are induced through the initial ionizing radiation event,” Tour said. — In preliminary tests at M.D. Anderson in July 2007, mice showed enhanced protection when exposed to lethal doses of ionizing radiation when they were given first-generation NTH drugs prior to exposure.”

Wrapping it up

1.     By far, the best protection against nuclear radiation is avoiding it.

2.     We do not know when the release of radioactive substances into the environment from the earthquake and tsunami-struck Fukushima Daiichi nuclear power plant in Japan will stop.  So far, efforts to bring the situation under control have not succeeded.

3.     Two radioactive substances of particular concern are iodine-131 and caesium-137.  These have already been released into the environment in large quantities due to the Fukushima disaster.  These substances are both highly radioactive and highly bioactive, being readily absorbed into human bodies.  Also of serious concern is plutonium, an extremely toxic byproduct of nuclear fission that has been found in the ground near the reactor sites. 

4.     Consequences from internal exposure to these substances can be most serious both in the short and long term.  Each of these substances in critical doses can cause death if left lodged in the body.

5.     Radiation from ingested radioactive substances originating from a nuclear accident is in some respects similar to radiation received from external sources, in some respects different.  The big dangers from of iodine-131, caesium-137 or plutonium come into play if they are absorbed into the body via breathing, eating or drinking them.  Caesium-137, for example, is readily absorbed from soil into certain vegetables and can enter the body effectively by eating such contaminated vegetables.

6.     Traditional means exist for removing these substances from bodies or preventing their absorption including use of potassium iodide, Prussian blue, and  DPTA.  These approaches should be pursued only under medical supervision.

7.     Effectively removing or preventing adsorption of iodine-131, caesium-137 or plutonium using these approaches takes time, may be only partially effective, and may still leave the result of substantial radiation injury under the best of circumstances.

8.     Antioxidants have been shown to be at least partially effective in reducing the damaging effects of radiation from external sources.  The known mechanisms of radiation damage suggests that the same should be the case for radiation from ingested sources.

9.     Research studies have established that a number of conventional antioxidants are protective against internal radiation damage including but not limited to resveratrol, alpha-lipoic acid, ginko biloba, beta carotene, curcumin, inositol, selenium, melatonin, vitamin C, vitamin E, N-acetylcysteine and ginseng(ref)(ref)(ref).

10.                        A number of new antioxidant and antioxidant combinations as well as other substances are being investigated for their superior abilities to protect against radiation.  How their effectiveness compares against that of conventional antioxidants is unknown.