I remember an old Star Trek movie where severely debilitated people without functional vocal chords could readily speak to each other by merely thinking their sentences.  Recent research is bringing us closer to having such a capability.  The article A Wireless Brain-Machine Interface for Real-Time Speech Synthesis in the current issue of Plos One lays out the progress.

“Brain-machine interfaces (BMIs) involving electrodes implanted into the human cerebral cortex have recently been developed in an attempt to restore function to profoundly paralyzed individuals. — In the current study we use a novel approach to speech restoration in which we decode continuous auditory parameters for a real-time speech synthesizer from neuronal activity in motor cortex during attempted speech. —  Neural signals recorded by a Neurotrophic Electrode implanted in a speech-related region of the left precentral gyrus of a human volunteer suffering from locked-in syndrome, characterized by near-total paralysis with spared cognition, were transmitted wirelessly across the scalp and used to drive a speech synthesizer. A Kalman filter-based decoder translated the neural signals generated during attempted speech into continuous parameters for controlling a synthesizer that provided immediate (within 50 ms) auditory feedback of the decoded sound. Accuracy of the volunteer’s vowel productions with the synthesizer improved quickly with practice, with a 25% improvement in average hit rate (from 45% to 70%) and 46% decrease in average endpoint error from the first to the last block of a three-vowel task.”

I take this to mean that machine-training is necessary and that generating normal fluent speech is not yet possible.  My impression is that a lot more needs to be done to understand and encode the relationships between neural events and continuous speech.  This may take some time.  Computer speech recognition research started in the 1950s and decent recognition of continuous speech was not achieved until around 2000.  The authors conclude “Our results support the feasibility of neural prostheses that may have the potential to provide near-conversational synthetic speech output for individuals with severely impaired speech motor control. They also provide an initial glimpse into the functional properties of neurons in speech motor cortical areas.”

I speculate that if and as this technology is perfected it would have a number of additional applications for normal non-debilitated people including:

·         Telephone calls without talking aloud for privacy or in noisy places or so as not to disturb others,

·         Rapid writing or recording of thoughts for people who can think faster than they can talk,

·         Private voice conversations not obvious to those you are with, even sneakier than text messaging can be, and

·         Controlling machinery or even driving a car with just internally vocalized thoughts.

In the future the situation could get even more extreme when electronics also can short-circuit the human hearing apparatus and thoughts can fly electronically from one brain into another.  I don’t want to go there for now.  If I live as long as I want to, however, there will surely come a point when I will have to decide whether or not to have a brain implant for voiceless speech synthesis.

It is time for a bit of humor.  I receive several advertiser-supported health, longevity and vitamin-promoting magazines in the mail.  I am not sure why they are getting sent to me since I don’t pay for them.  I usually have trouble finding much substance in them.  My intent here is to poke fun at them by constructing eleven cover-story titles and lead lines for a new magazine of that ilk which I will call AVOIDANCE.

AVOIDANCE

Live longer – the Dr. Goldstone method

Doctor Goldstone outlines his revolutionary approach to living longer, an extract from his book The Sure Way to Live Longer.  Long life is a matter of context, and the secret is ongoing death prevention.  “I guarantee you that if you succeed at avoiding death, you will live longer.”  Dr. Goldstone is a practicing coroner who knows his business and a frequent contributor to AVOIDANCE.

Flatten your bulgy belly

A simple guide based on the artichoke-lime juice diet, step climbing and squat jumps.  Blend boiled artichokes with the lime juice, refrigerate, and consume nothing but 3 cups a day for 2 weeks.  If A is your age and W is your weight you must climb |3*(W-A)| steps a day except on Fridays and do |(W-A)/3| squat jumps daily except on Tuesdays.  If you don’t follow instructions and your stomach stays bulgy, it’s your own fault.

Living with Zybbrignowski’s Symptom

It does not have to drive you crazy if you are willing to be bit nuts in the first place and chew a bunch of crunchy Forgouh Pain™ tablets whenever you feel an attack coming on.   Available in seven flavors, anti-allergenic.  Doctor-recommended.  Arsenic-free.  Convenient order form is below.  Order now.  Two bottles for the price of one.

Avoiding diseases of old age – a simple sports approach that is guaranteed to work

The solution is to die young, and this can likely be accomplished by pursuing a combination of dangerous sports.  We suggest parachute-free skydiving, ocean shark polo, motorcycle daredevil racing and Himalayan mountaintop skiing.

Forget your aging wrinkles with Azerbaijan koodo root slime grease

It burns and stings, smells terrible, won’t wash off, stains everything, ruins clothes and definitely makes your wrinkles seem like minor matters to be concerned about.

The six best ways to lose weight – and the 283 worst ways

Describes an annotated document you can buy for only $18.99 and keep by your refrigerator.  If you “act now” a dozen colorful anti-weight pebbles will be included for free.  Turns out, you better have strong eyeglasses or a magnifying glass handy to read the document.  It is written by the same lawyers that write contracts for software products, the ones where you have to click the “I agree” box to get the software to work.  You keep the anti-weight pebbles in a glass on the kitchen table to remind you not to eat.

Step up your sex life with exotic radish-garlic-spicy pepper soup

Five chopped up cloves of garlic, a generous sprinkling of dried red pepper flakes and a bottle of Tabasco sauce tops off the serving.  If you can manage to consume it and keep it down, in 24 hours you should be ready for a torrid sex experience.

Living simply for health

In other words, live simply for health and forget everything else.  It may not make you better but it can give you focus, purpose, and keep you reading Vince’s Blog.  And you can get so boring that you drive other pesky people away.  Hint:  if you are going to do this, be sure to get somebody else to pay your bills.

Bargain diet software makes healthy meal planning easy

Easy-to-use software for preparing tasty and healthful dishes, only $2.99 a disk.  Available formatted for Osborn I, Apple II, CPM, DOS, Commodore 64 and Atari 400 operating systems only. 

Dr Saps on how to forget your Alzheimer’s problems

His advice is to avoid unnecessary stress and worry.  Just ignore your dementia concerns and sooner or later you will surely forget them all.

Taking care of your hippocampus 

A nontechnical guide written in plain language for ordinary people who have heard of how important hippocampuses are. A clean, well-organized and well-functioning hippocampus is important for your emotional health and wellbeing, and for taking care of your hippo if you have one.  Emphasis should be on mitochondrial health and on a big enough hippocampus for your hippo to wander around in with African-type wallowing holes. 

I set out two days ago to see what updated research I could find on diet and cognition.  I found a bewildering array of items, some somewhat contradictory.  It has been a cognitive challenge to make sense of them, especially while having to deal with variety of other challenges like figuring out how to bring two virus-infected computers back to life, what to tell my investment adviser, how to take care of the house given that a big tree branch has crashed through a window, keeping things going during a couple of  storm-related power outages, and what I need to do to continue keeping a bunch of family members happy.  The question at hand is “What is the impact of diet on cognitive functioning and memory, especially for older people?”  So I report on a few selected 2009 studies and end up giving my own bottom line. 

Mediterranean diet and risk of dementia

The August 2009 report in JAMA Adherence to a Mediterranean Diet, Cognitive Decline, and Risk of Dementia. “ Objective:  To investigate the association of a Mediterranean diet with change in cognitive performance and risk for dementia in elderly French persons.   Design, Setting, and Participants:  Prospective cohort study of 1410 adults (65 years) from Bordeaux, France, — Adherence to a Mediterranean diet (scored as 0 to 9) was computed from a food frequency questionnaire and 24-hour recall. Main Outcome Measures”  Cognitive performance was assessed on 4 neuropsychological tests: Main Outcome Measures:  Cognitive performance was assessed on 4 neuropsychological tests: the Mini-Mental State Examination (MMSE), Isaacs Set Test (IST), Benton Visual Retention Test (BVRT), and Free and Cued Selective Reminding Test (FCSRT). Incident cases of dementia (n = 99) were validated by an independent expert committee of neurologists.  ^– Conclusions:  Higher adherence to a Mediterranean diet was associated with slower MMSE cognitive decline but not consistently with other cognitive tests. Higher adherence was not associated with risk for incident dementia.”  At least one commentary on the article in JAMA suggested that at least one of the other rests also may also indicate cognitive decline(ref).  Not much surprise here.

The DASH diet may slow cognitive decline – it you can get people to follow it

There is not much surprise for me in this July 2009 item either.  “A diet rich in fruits and vegetables and low in salt, sweets, and red meats — the Dietary Approaches to Stop Hypertension (DASH) model — appears to slow cognitive decline, researchers said here at the International Conference on Alzheimer’s Disease(ref).” “The patients received a score based on how closely they followed the diet, which requires seven to eight servings of grains; four to five servings of fruit; four to five servings of vegetables, two to three servings of low fat dairy, two or fewer servings of meat a day, and five servings of nuts or legumes or seeds a week.”  

“The groups were divided into quintiles, and the results showed that those patients in the highest quintile — the individuals who were closest in following the diet — had the slowest decline in cognitive functioning, while the patients in the lowest quintiles had the most rapid decline in functioning.  — Over the 11-year time frame of the study, the difference between the most diet-adherent individuals was about 3.73 points (P<0.001) on the Modified Mini Mental State Examination, a standard instrument that measures cognitive decline. The examinations were given at baseline and as many as four times during the study period.”

I think that the proponents of this diet are correct in pointing out that getting compliance with it is likely to be very difficult, even if it does offer benefits.

Rats on junk food become lazy and stupid

The August 2009 study Deterioration of physical performance and cognitive function in rats with short-term high-fat feeding seems to say that for rats at least, a high-fat diet leads not only to long-term cognitive decline but also to short-term decline as well.  “We found that rats ran 35% less far on a treadmill and showed cognitive impairment in a maze test with 9 d of high-fat feeding, with respiratory uncoupling in skeletal muscle mitochondria, associated with increased uncoupling protein (UCP3) levels. Our results suggest that high-fat feeding, even over short periods of time, alters skeletal muscle UCP3 expression, affecting energy production and physical performance.”

The Science Daily coverage of the research is headlined Do High-Fat Diets Make Us Stupid And Lazy? Physical And Memory Abilities Of Rats Affected After 9 Days.  According to it “All 42 rats were initially fed a standard feed with a low fat content of 7.5 per cent. Their physical endurance was measured by how long they could run on a treadmill and their short-term or ‘working’ memory was measured in a maze task. Half of the rats were then switched to a high-fat diet where 55 per cent of the calories came from fat. After four days of getting used to the new diet, the endurance and cognitive performance of the rats on the low- and high-fat diets was compared for another five days. — “With the standard feed, 7.5 per cent of the calories come from fat. That’s a pretty low-fat diet, much like humans eating nothing but muesli,” says Dr Murray. “The high-fat diet, in which 55 per cent of the calories came from fat, sounds high but it’s actually not extraordinarily high by human standards. A junk food diet would come close to that. — Some high-fat, low-carb diets for weight loss can even have fat contents as high as 60 per cent. However, it’s not clear how many direct conclusions can be drawn from our work for these diets, as the high-fat diet we used was not particularly low in carbs,” he adds. — On the fifth day of the high-fat diet (the first day back on the treadmill), the rats were already running 30 per cent less far than those remaining on the low-fat diet. By the ninth day, the last of the experiment, they were running 50 per cent less far. — The rats on the high-fat diet were also making mistakes sooner in the maze task, suggesting that their cognitive abilities were also being affected by their diet. The number of correct decisions before making a mistake dropped from over six to an average of 5 to 5.5.”

So, if people’s metabolisms are like rat’s, a steady diet of junk food could make us fat and lazy.  Some times when I am in a junk food chain late at night and noticing that everyone in sight is obese, I have had the same thought, a thought I quickly repress as being politically incorrect.

Unlike rats, airline pilots cognition is made better with a high fat or high carb diet

This next report is a mind-bender because it seems to contradict the previous one and to go against what we think we know.  The report is entitled High-Carb, High-Fat Diets Superior to High-Protein Diets in Improving Cognitive Performance.*   “Diets high in carbohydrates or fat can lead to significantly better cognitive-performance and in-flight-testing scores in pilots than diets high in protein, according to results reported in a poster presentation at the Military Health Research Forum (MHRF) 2009 in Kansas City, Missouri. — In addition, a high-carbohydrate diet helped study pilots sleep better, and a high-fat diet appeared to lead to significantly faster short-term memory. — Eating a diet that’s high in protein just isn’t going to help you perform optimally.   Results showed that overall flight-performance scores for the pilots consuming a high-protein diet were significantly worse (P < 05) than for those consuming a high-carbohydrate or a high-fat diet. A hierarchical regression analysis indicated that this was due in part to dietary protein intakes, serotonin levels, and irritability scores. — The response time on the Sternberg test of short-term memory was significantly faster for participants who ate the high-fat diet (P < .05) than for those who ate the protein and control diets, especially at higher memory loads. No significant impact was observed on the Vandenberg test.”

So does a high fat diet make cognition worse or improve it? Hmm.  Perhaps airline pilots can get smarter on junk food and rats can’t?  I doubt it.  Reminds me of the climate change studies.  Most of these say that CO2 is responsible for global warming, but a few say the opposite.  And I remember the old days when most research reports said cigarette smoking was very harmful and a few said the opposite.  In any event the presenter tempered the findings a bit.  “We’re certainly not saying you always have to eat high fat,” said Glenda Lindseth. “The take-away message is that a diet that is well balanced and has a lot of carbohydrates and a reasonable amount of fat in it is best for pilots to perform well cognitively(ref).”

What do I make of these reports?  Basically that nutrition research marches on, and that in general a single study or research report an important theory does not prove or disprove.  I think that there is plenty of additional evidence that the Mediterranean diet offers many health benefits likely to include increased cognitive clarity, and that high-fat diets are likely to create health problems.  See the blog post Recent research on the Mediterranean diet.  So most of these studies tend to confirm what is already known except for the airline pilot study.  Either that study will provide a breakthrough new perspective if the results are supported by additional studies, or additional research will cast doubt on or significantly narrow its conclusions. 

•  If you don’t belong to Medscape and want to read this item, do a Google search on the entire title and then click on it in the search results.

One hope for personalized medicine is that individuals would have their major gene variations profiled and that drug interactions with critical genes would also be profiled.  Thus, a person with a particular disease could determine whether a particular drug is efficacious given their gene variations, or whether that drug would be likely to produce an adverse reaction.  Fulfilling this hope requires both profiling of gene variations present in individuals and pharmacogenetic studies of drugs, that is, analyses and  clinical testing of how drugs behave in the presence of genetic variations.   I have discussed individual profiling in the blog entry Individual DNA testing. It is starting to get off the ground but has a very long way to go.  This blog posting is about progress/lack of progress in pharmacogenetic drug profiling. 

My comments are mainly based on a review article  that appeared in PloS ONE four days ago Fulfilling the Promise of Personalized Medicine? Systematic Review and Field Synopsis of Pharmacogenetic Studies.  The authors looked systematically at the published literature in an attempt to determine the current state of pharmacogenetic knowledge.  “From 102,264 Medline hits and 1,641 articles from other sources, we identified 1,668 primary research articles (1987 to 2007, inclusive). A high proportion of remaining articles were reviews/commentaries (ratio of reviews to primary research approximately 25:1). The majority of studies (81.8%) were set in Europe and North America focussing on cancer, cardiovascular disease and neurology/psychiatry. There was predominantly a candidate gene approach using common alleles, which despite small sample sizes (median 93 [IQR 40–222]) with no trend to an increase over time, generated a high proportion (74.5%) of nominally significant (p<0.05) reported associations suggesting the possibility of significance-chasing bias. Despite 136 examples of gene/drug interventions being the subject of ≥4 studies, only 31 meta-analyses were identified. The majority (69.4%) of end-points were continuous and likely surrogate rather than hard (binary) clinical end-points.” 

The state of progress appears to be underwhelming.  The authors conclude “The high expectation but limited translation of the pharmacogenetic research thus far may be explained by the preponderance of reviews over primary research, small sample sizes, a mainly candidate gene approach, surrogate markers, an excess of nominally positive to truly positive associations and paucity of meta-analyses. Recommendations based on these findings should inform future study design to help realise the goal of personalised medicines.” 

So, more or less the same thing can be said about the pharmacogenetic profiling aspect of the personalized medicine hope:  It is starting to get off the ground but has a very long way to go. It is a long long way to Tipperary, to stem cell treatment and to drug-response related personalized medicine.  At least, we are on our way.

My anti-aging firewalls treatise characterizes 14 major theories of aging and 6 additional “candidate” theories of aging.  Up until yesterday and I thought I had come to the end of the line with respect to new aging theories.  However my blog reader jeg3 identified a publication that changed my mind in a comment posted on December 3.  So I will soon be adding a seventh candidate theory of aging to my treatise.  The publication was published in 2008 but somehow escaped by attention until now: Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage.  It is by Bruce N. Ames, a giant in the field of anti-aging science. 

The new theory is based on two well-documented observations.  The first observation is that most of us do not consume adequate quantities of a number of important micronutrients, these including minerals like zinc, iron, copper, magnesium, calcium, potassium and selenium and vitamins like D, B12, folic acid, pyridoxine, pantothenate, riboflavin, and biotin.   The second observation is that evolution built our bodies so as always to opt for short-term survival over long-term wellbeing whenever there a need to choose between the two.  A familiar example is the “fight or flight” response in case of an emergency. A flood of cortisol is released that speeds up our responses and facilitates us to react quickly.  The price is a weakening of our immune response and a shortening of our telomeres(ref),  events that tend to be life-shortening.  Thus, evolution seems to reason that it is better to live a bit less-longer at the end of our lives than to risk being eaten by a tiger or being killed in an auto crash while younger. 

The Micronutrient triage theory of aging essentially says that the body is very intelligent in its allocation of micronutrients, allocating them according to triage priorities favoring short-term functionality over long-term health.  The topmost priorities are for minute-to-minute and day-to-day body functioning, immediate energy metabolism, keeping up circulation and blood pressure, maintaining digestion and things like that.  The lowest priorities are those that make for longevity: keeping up a strong antioxidant response, DNA damage repair, minimization of glycation and excess inflammation, prevention of senescence, preservation of telomere lengths, and matters like those.  When not enough of a micronutrient is available to handle the low-priority needs, those needs are left unmet.  The consequences may be completely unnoticed in day-to-day experience but are likely to show up late in life as cancers, Alzheimer’s disease, Parkinson’s disease, diabetes, cardiovascular diseases and the other maladies that kill older people.  

Ames summarizes his theory this way “I propose DNA damage and late onset disease are consequences of a triage allocation response to micronutrient scarcity. Episodic shortages of micronutrients were common during evolution. Natural selection favors short-term survival at the expense of long-term health. I hypothesize that short-term survival was achieved by allocating scarce micronutrients by triage, in part through an adjustment of the binding affinity of proteins for required micronutrients. If this hypothesis is correct, micronutrient deficiencies that trigger the triage response would accelerate cancer, aging, and neural decay but would leave critical metabolic functions, such as ATP production, intact.”  

Supporting the theory is the fact that deficiencies in a large number of micronutrients seem to produce the same kinds of DNA damage produced by radiation.  “Approximately 40 micronutrients are required in the human diet. Deficiency of vitamins B12, folic acid, B6, niacin, C, or E, or iron, or zinc, appears to mimic radiation in damaging DNA by causing single- and double-strand breaks, oxidative lesions, or both(ref).’   

Ames cites a formidable collection of research studies to support his theory and builds a strong case for it.  Ames, you may recall, has long been a key researcher in the areas of mitochondrial functioning, DNA damage and the roles of micronutrients(ref).  He was also the lead researcher involved in the discovery of the impact on mitochondrial health of the Acetyl-l-carnitine and alpha-lipoic acid combination back 7 years ago(ref), a supplement combination suggested in my anti-aging firewalls supplement regimen.   If you have never been in Ames’ presence you can get a sense of the man and what he about by viewing his online lecture Understanding Aging.   

A problem of course is that micronutrient needs can vary by age, individual, and individual circumstances, and further studies are needed to nail these down.  “The elderly may need more or less of certain vitamins and metabolites compared with younger people, but this issue has not been thoroughly examined(ref).”  The situation is further complicated in that, for many micronutrients like iron, DNA damage can be produced by either too much or too-little of then.   In general in our society, however, most of us get too little of several critical micronutrients rather than too much. 

Ames points out that seven micronutrients (pyridoxine, pantothenate, zinc, riboflavin, iron, copper, and biotin) are particularly important because they are required for heme synthesis in mitochondria.  “It is likely that a deficiency in any of these seven will cause a deficit of heme and therefore of complex IV, of which heme-a is an essential component  — The normal complement of complex IV keeps oxidants to a minimum; deficits of complex IV result in oxidant leakage, DNA damage, accelerated mitochondrial decay, and cellular aging(ref). “ 

In the publication, Ames strongly advocates micronutrient dietary supplementation.  “Evidence is accumulating that a MVM (multivitamin-mineral) supplement, or smaller combinations of vitamins and minerals, also improve long-term health, reducing heart disease, cancer, and cataracts and improving immune function for those who consume inadequate diets.” 

The good news for followers of my anti-aging firewalls supplement regimen is that that almost all the micronutrients mentioned in the Ames publication are included in ample quantities in the regimen: vitamins B-6, C, D, B-12, A, pyridoxine, riboflavin, pantothenate, folic acid, biotin, zinc, calcium, magnesium,  copper, selenium, omega-3 fatty acids, tocopherol, and  lycopene.  The main micronutrient discussed by Ames but missing from the regimen is iron.  I have not included iron in my supplement regimen because it is included in many foods I normally eat (see this listing) and because it creates damage when in excess.  Also, vitamin C, which I take in generous quantities, facilitates iron absorption.  My regimen contains a B-complex tablet, and I depend on this for riboflavin and biotin.  And there are many additional micronutrients in the regimen that are not mentioned in the Ames paper like Vitamin K and a number of powerfully-acting phytochemicals. 

I will include the The micronutrient triage theory of aging as the 7^th candidate theory of aging in the next update of my treatise.

In the last 2-3 years there is has been a lot of excitement in research circles about brown adipose tissue, in other words, brown fat.  Brown fat, long known to exist plentifully in babies and rodents, is rich in turned-on mitochondria and blood vessels.  Unlike white fat, brown fat burns energy at a ferocious rate.  In adults, however, it tends to be scarce and concentrated around the neck and has been traditionally thought to play a relatively minor role in adult human metabolism.  The newer research suggests a different picture.  Brown fat can be very important for metabolism.  Further, the creation of brown fat can be induced by turning on a certain gene and that induction of brown fat could possibly play a major role in public health by controlling or even eliminating obesity.

About brown fat

Brown fat keeps tiny critters in the wild warm and is important for us too.  “Cold-induced adaptive (or nonshivering) thermogenesis in small mammals is produced primarily in brown adipose tissue (BAT).  BAT has been identified in humans and becomes more active after cold exposure. Heat production from BAT requires sympathetic nervous system stimulation, T3, and uncoupling protein 1 (UCP1) expression(ref).”  When animals are exposed to cold, the expression of the UCP1 gene is upregulated to activate the production of heat.  UCP1, also known as thermogenin, “allows the leak of protons in respiring mitochondria, dissipating the energy as heat; the enzyme has an important role in nonshivering heat production induced by cold exposure or food intake(ref).” 

A little brown fat can go a long way towards burning food energy and total metabolism. “Brown fat cells have been found in adults, in the lower part of the neck just above the collarbone. The region of brown fat cells in the neck was tested by placing five volunteers, in thin clothing, in a chilly room for a couple of hours. The researchers then investigated this region by PET scanning and discovered that metabolism there was on average 15 times higher than in the neighboring white fat tissue. The result suggests that the brown fat may play a significant role in metabolism(ref).” 

So, researchers have reckoned that if they could find a safe and easy way to increase the ratio of brown fat to white fat in adults, that might go a long way towards having a skinnier, healthier less-obese population.  “It has been suggested that manipulating the development of fat cells so that they become brown fat cells rather than white fat cells might be an approach to treat obesity(ref).” 

Recent research related to creating brown fat

A number of important discoveries have been made, one reported today in a news item in Science Daily Brown Fat Cells Make ‘Spare Tires’ Shrink; Promising New Approach to Combat Obesity.  “Scientists at the University of Bonn have found a new signaling pathway which stimulates the production and function of so-called brown fat cells. They propose using these cells that serve as a “natural heating system” in order to just ‘burn’ unwanted excess fat. — The scientists were now able to show which signals prompt the body to produce brown fat cells. A signaling pathway which is controlled by the PKG enzyme takes on a key role in this process. This signaling pathway results in the stem cells of the fatty tissue becoming brown fat cells. For this it switches on the mass production of mitochondria and ensures that UCP is formed — .  — Furthermore, we were able to show that PKG makes brown fat cells susceptible to insulin,” –. “Therefore PKG also controls how much fat is burnt in general.”

This research result follows an important discovery in 2008 that myoblasts, muscle cell progenitor cells, can not only differentiate so as to  produce replacement muscle cells when activated by appropriate signals, but also can differentiate to produce brown fat cells when a gene called  PDRM16 is turned on(ref)(ref). See Making ‘Good’ Fat From Muscle And Vice Versa.

This followed a discovery in 2007 that when PRDM16 genes are inserted into white fat precursors, the precursor cells produce brown fat cells instead of white ones(ref)(ref). “Spiegelman (the lead researcher in this work) said the finding confirms that PRDM16 is the “master regulator” of brown fat development(ref).”  Finding a drug or supplement that activates the PRDM16 gene is therefore a possible strategy for controlling weight and obesity in humans.  Another possibility might involve “transplanting PRDM16-equipped white fat precursors into people who are at high risk of becoming obese, to shift their metabolism slightly into a calorie-burning mode(ref).” 

Are there dietary supplements that differentially promote the creation of brown fat and therefore higher metabolism so as to control weight?  Quite possibly, but my impression is that research in this area is just getting off the ground now.  I have seen several supplement-vending sites that talk about brown fat and vaguely suggest that their supplements may help create it – but they provide no research backup for such claims.  Doing some quick and possibly superficial searching, I found relevant research on only one supplement, the amino acid l-arginine.  Several studies suggest that l-arginine increases lean body mass in obese rats.  And the title of this 2009 publication tells its basic story: Dietary L-arginine supplementation reduces white fat gain and enhances skeletal muscle and brown fat masses in diet-induced obese rats.  L-arginine is sometime advertised as a weight loss substance, as a sexual stimulant, and (combined with other amino acids) as a promoter for the expression of human growth hormone.  Because of a bad experience I had resulting from heavy use of l-arginine several years ago (a bout of arthritis), I have since personally avoided it.  

I expect to see a number of additional research publications on dietary supplements and brown fat in the coming year or two and will report on these as I come across them.   

If you have pet mice suffering from colitis, the probiotic Bacillus Polyfermenticus can help them recover from it according to a 2009 study(ref).  “Mice treated with B. polyfermenticus during the non-inflammatory period of the disease had reduced rectal bleeding, their tissues were less inflamed and they gained more weight than mice that did not receive the treatment.”  This and other probiotics are likely to offer similar and additional benefits to us humans. 

“The study occurred in two phases, one involving live mice with colitis and another that looked at human intestinal cells in a test tube. The mouse study showed that B. polyfermenticus facilitated the recovery of mice from colitis. The mice showed reduced rectal bleeding, less inflamed tissue and they gained more weight than the mice that did not receive B. polyfermenticus. The study also found that the colon tissue of the treated mice had greater angiogenesis, a process that is necessary for wounds to heal. — The test tube study allowed an in-depth look at what happens at the cellular level when human intestinal microvascular endothelial cells are exposed to B. polyfermenticus. This phase found that the probiotic treatment encouraged several steps that are part of the angiogenic process, including the migration of cells and the formation of new blood vessels. — The test tube studies also uncovered how this happens. The researchers found that B. polyfermenticus increases the production of Interleukin-8 (IL-8), a substance that enhances angiogenesis. The study also found that IL-8’s receptor, CXCR2, and a cellular pathway, known as NF-κB, play a critical role in the angiogenic process(ref).”

The 2009 research report Bacillus polyfermenticus ameliorates colonic inflammation by promoting cytoprotective effects in colitic mice concludes “Treating colonic epithelial cells with B. polyfermenticus-conditioned medium (BPCM) enhanced cell proliferation and induced the phosphoinositide 3-kinases/Akt signaling pathway, suggesting that this bacterium can promote epithelial cell proliferation. BPCM also promoted the migration of colonic epithelial cells. These data suggest that B. polyfermenticus ameliorates colonic inflammation by suppressing apoptosis and promoting epithelial cell proliferation and migration.”

Other current research as well as prior research studies also support potential health benefits of bacillus polyfermenticus.  The 2009 report The anti-cancer effect of probiotic Bacillus polyfermenticus on human colon cancer cells is mediated through ErbB2 and ErbB3 inhibition concludes “These results show that B.P. inhibits tumor growth and its anti-cancer activity occurs, at least in part, through suppressing ErbB2 and ErbB3. Taken together, our study suggests that this probiotic may be clinically used as a prophylactic treatment to prevent colon cancer development.”

The 2007 research report A Probiotic Strain of Bacillus polyfermenticus Reduces DMH Induced Precancerous Lesions in F344 Male Rat  states “In this study, we have assessed the effects of B. polyfermenticus on the antioxidant system and the process of colon carcinogenesis in male F344 rats. — These data indicate that B. polyfermenticus exerts a protective effect on the antioxidant system and the process of colon carcinogenesis, thereby suppressing the development of preneoplastic lesions.”

The 2006  report Dietary Supplementation of Probiotic Bacillus polyfermenticus, Bispan Strain, Modulates Natural Killer Cell and T Cell Subset Populations and Immunoglobulin G Levels in Human Subjects concludes “This study suggests that the supplementation of B. polyfermenticus has a potentially positive effect on immune function by enhancing IgG production as well as by modulating the number of immune cell population such as CD4+ and CD8+ T cells and NK cells.”

Other research reports indicating benefits of probiotics include M1198 Lactobacillus Rhamnosus GG Prevents Radiation Induced-Small Intestinal Injury in a MyD88 Independent, But COX2 Dependent Manner, M1199 Counterbalancing Dysbiosis in Crohn’s Disease: Faecalibacterium Prausnitzii, a Major Commensal Bacterium, Exhibits In Vitro and In Vivo Anti-Inflammatory Effects,   and M1200 Probiotic E. coli (Symbioflor®2) Treatment Mediates Antimicrobial β-Defensin (HBD-2) Synthesis and Fecal Excretion in Humans.

Here is where I have to admit a slip-up.  For nearly two years now my personal supplement regimen has included a morning multi-strain probiotic capsule.  However, somehow I have not included that supplement in my anti-aging firewalls Supplement Regimen.  I will add it in when I do my next update of the treatise, probably within 24 hours. Based on the above-cited research I am also looking for probiotic capsules which contain B. polyfermenticus, a microbe that appears not to be included in most mainline commercial US probiotic products. 

I became fascinated with l-carnosine about ten years ago.  Back then, this substance seemed capable of doing more or less what telomerase activators are hoped to be doing now – greatly extending the replicative life spans of certain body cells.  So I started studying l-carnosine intensively and also taking it as a supplement.  And I am still doing that.  The substance clearly has significant anti-aging powers but some of the ways in which it works are still shrouded in mystery. 

L-carnosine does a number of very good things for health and longevity.   I wrote a review of the substance in 2002 and there I said, listing multiple literature citations, “Carnosine can inhibit non-enzymic glycosylation of proteins.  Carnosine blocks the formation of AGEs  protecting against cross-linking of proteins in the eye lense and skin collagen, cross-linking of proteins to DNA molecules, and formation of other abnormal proteins.  Carnosine promotes wound healing, and has numerous anti-oxidant properties including the quenching of  singlet oxygen.  Carnosine traps peroxyl radicals, inhibits damage due to gamma irradiation, binds transition metals rendering them unable to participate in the toxin-producing Fenton’s reaction.  Carnosine may go beyond scavenging ROS to reducing the production of ROS.  It protects against and promotes healing of stomach ulcers and reduction of brain damage due to accumulation of beta amyloid and possibly due to malondialdehyde or hypochlorite anions.  It can very likely be used as an anti-ischemic drug.  Carnosine is an efficient chelating agents for copper and other transition metals, and Carnosine appears to protect neurons from zinc- and copper-mediated neurotoxicity.  Carnosine appears to expand the resistance of rats to various induced stresses.  It can be used in the treatment o severe gingivostomatitis.  Carnosine  is an immunostimulant.  Carnosine is reported to have an ability to up or down-regulate cellular and enzymatic processes to bring them into normal range.  For example, Carnosine can decrease platelet aggregation in patients with low clotting indices.  The list goes on and on.  One study by Egyptian researchers even suggests that Carnosine could be used to correct metabolic disturbances induced by schistosomiasis.”

But the one reported fact about carnosine that really attracted my attention was that it could significantly delay or reverse cellular senescence.  This was long before the days of telomerase activation.  I wrote “Research studies by Mcfarland and all going back to 1994 indicate that Carnosine can delay senescence and promote formation of a more juvenile phenotype in cultured human fibroblasts, extending the Hayflick limit for reproduction of such cells by up to ten doublings.  Late-passage fibroblasts from lung and foreskin tissues were switched back and forth a number of times between Carnosine-enhanced and non-enhanced culture media.   Mcfarland and his colleagues consistently observed that the Carnosine culture medium restored the juvenile cell phenotype within days, whereas immersion in the standard culture medium brought back the senescent cell phenotype(ref).  The life span of cells immersed in the Carnosine medium was also increased, even for old cells. When late-passage lung fibroblasts at 55 PDs (population doublings) were transferred to the Carnosine medium, they lived to 69 to 70 PDs, compared to 57 to 61 PDs for the fibroblasts that were not transferred. Further, the fibroblasts transferred to the Carnosine medium attained a life span of 413 days, compared to 126 to 139 days for the control fibroblasts.  Finally, it appears that when cells in the Carnosine medium eventually enter into cellular senescence, they nevertheless retain a normal or less-senescent morphology.“  

On a cellular level, l-carnosine extended the lifespan of the fibroblasts by a factor of about 3, and this fact really grabbed me. And now that I start to think about it again, it still grabs me.

This led me back then to conjecture that perhaps l-carnosine caused the expression of telomerase or some other telomere-protecting protein and therefore had extraordinary anti-aging power.  But other experts in longevity I consulted at the time, having their own fish to fry, had no patience for that idea. 

A 2004 publication L-carnosine reduces telomere damage and shortening rate in cultured normal fibroblasts  confirmed the earlier Mcfarland observations.  “In this work, we studied the effect of carnosine on the telomeric DNA of cultured human fetal lung fibroblast cells. Cells continuously grown in 20 mM carnosine exhibited a slower telomere shortening rate and extended lifespan in population doublings. When kept in a long-term nonproliferating state, they accumulated much less damages in the telomeric DNA when cultured in the presence of carnosine.  We suggest that the reduction in telomere shortening rate and damages in telomeric DNA made an important contribution to the life-extension effect of carnosine.” 

On the one hand, this capability of carnosine to greatly extend the number of cell doublings excited me greatly at the time and still intrigues me.  Even today, precious few substances seem to have that kind of anti-aging potential.

On the other hand, how carnosine works to extend the number of cell doublings so greatly was then and is still now a mystery.  I further wrote “The mechanism by which Carnosine can extend the Hayflick limit appears to be unknown, though in my mind at least it is possibly the most central issue with respect to Carnosine and longevity research.  Various  possibilities appear to exist, including:  1.  The ROS-scavenging properties of Carnosine significantly reduce damage of telomeric DNA thus extending the maximum number of divisions possible. 2.  As put by Hipkiss “Perhaps the carbonyl binding activity of Carnosine (or the released histidine) might mask any deleterious effects of the aberrant (carbonyl) protein on proteasome function as well as facilitate degradation  to allow the extras cell divisions;” and, 3.  Through some sequence of Carnosine-induced gene transcription and protein release, telomerase is expressed in the cells involved leading to longer telomeres and consequently more extended cell replication cycles.”

As I became more engaged in other areas of anti-aging research around 2003, this unusual capability of l-carnosine slipped to the back of my mind.     However, I just ran across a 2009 publication that brings the enigmatic character of this substance up again.  The publication is appropriately titled On the enigma of carnosine’s anti-ageing actions.  “Carnosine (beta-alanyl-L-histidine) has described as a forgotten and enigmatic dipeptide. Carnosine’s enigma is particularly exemplified by its apparent anti-ageing actions; it suppresses cultured human fibroblast senescence and delays ageing in senescence-accelerated mice and Drosophila, but the mechanisms responsible remain uncertain. In addition to carnosine’s well-documented anti-oxidant, anti-glycating, aldehyde-scavenging and toxic metal-ion chelating properties, its ability to influence the metabolism of altered polypeptides, whose accumulation characterises the senescent phenotype, should also be considered. When added to cultured cells, carnosine was found in a recent study to suppress phosphorylation of the translational initiation factor eIF4E resulting in decreased translation frequency of certain mRNA species. Mutations in the gene coding for eIF4E in nematodes extend organism lifespan, hence carnosine’s anti-ageing effects may be a consequence of decreased error-protein synthesis which in turn lowers formation of protein carbonyls and increases protease availability for degradation of polypeptides altered postsynthetically. Other studies have revealed carnosine-induced upregulation of stress protein expression and nitric oxide synthesis, both of which may stimulate proteasomal elimination of altered proteins. Some anti-convulsants can enhance nematode longevity and suppress the effects of a protein repair defect in mice, and as carnosine exerts anti-convulsant effects in rodents, it is speculated that the dipeptide may participate in the repair of protein isoaspartyl groups. These new observations only add to the enigma of carnosine’s real in vivo functions.”

So the enigma remains unresolved.  In fact the author AR Hipkiss has been an important leader in l-carnosine research all along, having also published some 30 documents having to do with l-carnosine in the last 10 years, including:

Chapter 3 carnosine and its possible roles in nutrition and health. (2009) “Physiologically carnosine may help to suppress some secondary complications of diabetes, and the deleterious consequences of ischemic-reperfusion injury, most likely due to antioxidation and carbonyl-scavenging functions.”

Carnosine, diabetes and Alzheimer’s disease (2009)

Could carnosine or related structures suppress Alzheimer’s disease? (2007) “Protein oxidation and glycation are integral components of the AD pathophysiology. Carnosine can suppress amyloid-beta peptide toxicity, inhibit production of oxygen free-radicals, scavenge hydroxyl radicals and reactive aldehydes, and suppresses protein glycation.” – “Carnosine stimulates proteolysis in cultured myocytes and senescent cultured fibroblasts. These observations suggest that carnosine and related structures should be explored for therapeutic potential towards AD and other neurodegenerative disorders.”

Would carnosine or a carnivorous diet help suppress aging and associated pathologies? (2006) “Carnosine has the potential to suppress many of the biochemical changes (e.g., protein oxidation, glycation, AGE formation, and cross-linking) that accompany aging and associated pathologies. Glycation, generation of advanced glycosylation end-products (AGEs), and formation of protein carbonyl groups play important roles in aging, diabetes, its secondary complications, and neurodegenerative conditions. Due to carnosine’s antiglycating activity, reactivity toward deleterious carbonyls, zinc- and copper-chelating activity and low toxicity, carnosine and related structures could be effective against age-related protein carbonyl stress.”

Does chronic glycolysis accelerate aging? Could this explain how dietary restriction works? (2006) {VG comment: To the extent that chronic glycolysis does accelerate aging, then perhaps l-carnosine’s powerful anti-glycating action could explain some of its anti-aging capability.}

On the mechanisms of ageing suppression by dietary restriction-is persistent glycolysis the problem? (2005) {Same VG comment}

Could carnosine suppress zinc-mediated proteasome inhibition and neurodegeneration?   Therapeutic potential of a non-toxic but non-patentable dipeptide. (2005)

Glycation, ageing and carnosine: are carnivorous diets beneficial? (2005) {VG comment:  Meat-eating has a bad reputation in health circles today.  In this and other articles, Hipkiss points out that meat-eating has some good things going for it too.}

Other researchers have continued to publish about l-carnosine. However the mechanism of how l-carnosine can so greatly extend the replicative life of certain cell cultures and extend the life of lower organism has never been satisfactorily explained as far as I am concerned. In 1999 leading l-carnosine  researchers wrote in the publication Carnosine as a Potential Anti-senescence Drug “Anyway, the question “How could such a small molecule have such profound effects?” remains unanswered, though we hope through increased global scientific collaboration that we shall have the answers sooner rather than later.”  Now, ten years later, the question still remains unanswered.

One thing is for sure though.  L-carnosine will continue to be part of my suggested anti-aging Supplement Regimen and I will continue taking it, currently 500mg twice daily.

Light metals may not lengthen lives but heavy metals can certainly shorten them.  Toxicity due to heavy metals can inadvertently come about many ways: drinking slightly acid water that has passed through lead pipes, eating too much mercury-containing tuna and swordfish, eating flakes of lead paint that have dropped from the ceiling in an ancient kitchen, breathing fumes from a nearby smelter, oil-painting with cadmium red and yellow, and breathing mercury vapor from smashed fluorescent bulbs.  A man named Orlando used to work in my granddad’s newspaper running a linotype machine back in the 30s in Detroit.  Those machines had pots of boiling lead used to cast type, and Orlando was strange and crazy from breathing the fumes.  Mercury used to be used extensively in shaping the felt used in hats and drove hatters to become mad, thus the phrase ‘mad as a hatter.” A few years back a test showed I had a high level of serum arsenic.  That was probably from handling pressure-treated lumber restoring the deck in my summer home.  

“Symptoms of heavy metal toxicity include mental confusion, pain in muscles and joints, headaches, short-term memory loss, gastrointestinal upsets, food intolerances/allergies, vision problems, chronic fatigue, and others. The symptoms are so vague that it is difficult to diagnose based on symptoms alone(ref).”  Therefore I strongly recommend that any readers who believe they may be suffering from heavy metal poisoning should consult with a medical practitioner to obtain proper testing and treatment.  And, of course, epigenomic deregulation and accelerated aging can result from the presence of heavy metals in the body.  In extreme case, death may soon follow the poisoning.

Dangerous heavy metals include arsenic (found in insect and other pest poisons, in some industrial products and even in some drinking water), lead (found in old-fashioned paints, old plumbing pipes and even new soldered plumbing joints, old lead house paint, old toys and some toys from China, , and fumes from smelters),  mercury (found in large ocean fish and some fish from contaminated waters, fluorescent light bulbs in vapor form, dental fillings, thermometers, fumes from some coal-burning power plants, mining ore processing and foods containing mercury residues from processing), and cadmium (contained in fumes and wastes from various industrial processing, silver soldering, nickel plating, engraving, electroplating, and used in nickel-cadmium batteries as well as cadmium vapor lamps.)  These and other toxic heavy metals (there are about a dozen, all told) are also used in agriculture, in treating parasites in farm animals and often find their way into water and air associated with industrial or agricultural pollution.

Clearing out heavy metals

The sources of heavy metals are so universal that it may be impossible to avoid having some levels of one or more of them in one’s system, but yet the ideal body levels of all such metals is zero.  So, what are the ways of getting rid of heavy metals from one’s body?  I know of three approaches:

–         Intravenous chelation

The standard medical treatment for acute heavy metal poisoning is intravenous chelation, usually with EDTA.  A chelating substance can be thought of as chemical tongs which can grab toxic heavy metal molecules and escort them outside of the body.  “The Chelation process is based upon the use of a water soluble molecule such as EDTA, that can essentially wrap itself around a heavy metal molecule that ISN’T water soluble, and gets trapped inside the body because it cannot pass through the mucous membranes of the kidneys, liver, GI tract, lungs or skin. — The word “CHELE” is Latin for the claw of a crab, and the Chelation process is essentially as if a “Crab claw” wraps itself around a heavy metal molecule, and then gives it free passage out of the body (similar to an illegal alien sneaking across the border in the trunk of a car)(ref). “  The calcium EDTA is dripped into a vein and the chelated metals pass out in the urine. The IV treatments may last 15-30 minutes each and, depending on the degree of toxicity present, a number of treatments may be required.   Other intravenous chelators include DMPS and  DMSA.  The intravenous chelating process also removes desirable nutrients like zink, vitamins C and E which must be replenished.

Intravenous EDTA treatment is FDA-approved for certain indications, generally regarded to be safe and is usually the treatment of choice in case of acute heavy metal poisoning.  However, its widespread use by some practioners of alternative medicine is highly controversial.  These practioners believe that even minor heavy metal toxicity may be responsible for a wide variety of illnesses, including circulatory diseases, and suggest repeated use of intravenous chelation(ref).  They make claims like “EDTA Chelation has been proven effective in the elimination toxins and dangerous arterial plaque in hundreds of medical studies conducted by many of the world’s most highly respected medical institutions over 50 years(ref).”  Twenty, thirty or more sessions of this therapy may be recommended, often to be done in clinics owned by such practioners themselves. 

However, many cardiovascular experts associated with mainline medicine believe that such research claims are vastly exaggerated and question the efficacy of this approach for other than treating acute poisoning(ref).  The paper EDTA chelation therapy for cardiovascular disease: a systematic review concludes “The best available evidence does not support the therapeutic use of EDTA chelation therapy in the treatment of cardiovascular disease. Although not considered to be a highly invasive or harmful therapy, it is possible that the use of EDTA chelation therapy in lieu of proven therapy may result in causing indirect harm to the patient.”

–         Oral supplements that are chelators

As already well-stated in my treatise “While acute poisoning with excessive blood serum levels of PCBs, lead, arsenic, cadmium or mercury requires intravenous chelation and other aggressive treatments, supplements can play a role in ongoing control of serum levels of these substances in healthy individuals and on the biological impacts of the presence of such toxins.  L-carnosine is an important element of my firewall defense against toxic heavy metals like cadmium, lead, and mercury since it has an ability to chelate them (literally, to grab on to and combine with the molecules of these metals so the kidney and liver can excrete them).  Further, according to animal experiments, certain antioxidants already in this firewall, vitamin C, alpha tocopherol, melatonin and alpha-lipoic acid in particular, can play roles in reducing the toxicity of heavy metals and PCBs, in some cases reducing it dramatically.   Other components of the firewall defense against toxic metals are mineral supplements that compete for absorption and compete metabolically with such metals.   For example, copper and selenium antagonize mercury.  Calcium helps reduce lead and zinc helps reduce cadmium.  Magnesium also appears to be very important for protecting cells from heavy metals.”  And, pyridoxamine is also a chelator.

Although I had a few sessions of intravenous chelation many years ago, I now rely on the supplements to do the job.  If I were inadvertently exposed, say, to mercury or arsenic fumes, I would consider a few sessions of IV EDTA treatment.

–         Toxic metal removal by raising body heat and sweating

In a recent blog commentary, reader Jayne pointed out the use of sweating in saunas as a way of getting rid of heavy metals, an approach I had not heard of until then.  There are lots of research citations relating to the role of raising body heat and sweating in elimination of “good” minerals such as calcium, magnesium, potassium and zink(ref)(ref).  In fact, that’s why people who exercise drink Gatoraade to replenish their electrolytes.  There are also mentions in Internet of the use of saunas for “detoxification,” particularly detoxification after exposure to PCBs or solvents(ref)(ref).  I found a couple of casual mentions of the use of saunas for heavy metal removal in the medical literature(ref), and several mentions on commercial sauna sites(ref).  My limited searching has failed, however, to reveal any systematic studies relating sauna use to heavy metal detoxification.  So, I am unable to determine how effective this approach to detoxification may actually be, how hot the sauna has to be, how long to stay in it, safety precautions, etc. 

Beyond saunas, sweat lodges rituals involving intense heat are processes with native-American origins that are supposedly detoxifying.  I went through a few of those a couple years back and the heat stress was so great that I was glad to emerge alive.  A few weeks ago a news report said that three people were killed and nearly two dozen more required hospital treatment due to participating in such a ritual.  So, my fears were not entirely unjustified. Intense sustained heat can be very dangerous.

Any of you readers out there who are members of the sauna or sweat lodge cultures might want to chime in on this.  I have a large sauna at home but family members have gradually filled it with storage boxes.  The same has happened to my sauna at the lake house.    If I were sufficiently motivated I would mobilize efforts to clear them out and start using them again.

A few hours ago a dear friend of mine asked me to review the supplements he was taking before he flew away to live in Germany.  To provide a context for that review I came up with a simplified explanation of what aging is and what can be done about it.  Given how complex my treatise ANTI-AGING FIREWALLS –  THE SCIENCE AND TECHNOLOGY OF LONGEVITY has become, I thought it might be useful for many of my readers to lay out the same simplified explanation.   

What is aging?

Aging is the lifelong accumulation of changes in the DNA surrounding our genes that result in changing gene expression.  These are called epigenomic changes, and have to do with turning our various genes off and on so to produce the observed phenomena of aging.  These phenomena can include wrinkled skin, balding hair and decreased libido.  More importantly, they include gradual but generalized deregulation of body processes, degeneration of organs and increasing susceptibility to disease processes. This increasing deregulation, degeneration and disease susceptibility may start in subtle ways around age 30 or before and gradually accelerates thereafter.  The curve of impending sickness and death becomes ever more ominous with advancing age.  Nobody dies of old age per-se.  Everybody dies of something, however, like heart failure, diabetes, cancer, stroke, pneumonia or accident, almost all of us by age 110.  We die because the epigenomic changes make the curves of our vulnerability to exactly these causes of death become steeper and steeper  – until the odds of anyone continuing to live go down to zero.  Some people with defective genes may typically die earlier and others with exceptional genes may experience the curve of degeneration slower.  See yesterday’s post paying attention to the item on Centenarian Ashkenazi Jews, but even they die off before 122.  

So, there is a program of aging.  If aging were not programmed there would be an exceptional tiny few of us who lived on to 200, 300 and even 500 and some dogs would live to 150.  Every species has such a program.  Why such a program?  Probably because evolution protects species, not necessarily members of a species.  Evolution operates so as to clear out older members of species who have already raised offspring so they won’t compete for resources with younger ones.   The aging program changes everything in our bodies.  Thousands of genes get switched off and on.  Our hormone levels decrease, our nervous systems become less responsive and so do all the body feedback systems that support us, our immune systems become progressively weaker.  We can gain too much weight; lose our strength, become susceptible to inflammatory processes, and lose eyesight, balance, memory and ability to think.  As we age, one kind of sickness can speed the deteriorative process and lead ever-more quickly to another sickness and then another.  Things that we could fight off quickly in youth become ever-more deadly.  A minor cold can lead to pneumonia and death.  A splinter in a finger can lead to a MRSA infection, hospitalization and death. What are the aspects of the aging program and how do they work?  These are complicated topics treated in my treatise and many earlier blog entries.   

Anti-aging strategies 

The anti-aging strategies available to us are few, including:

o    Avoid causes of accelerated aging

o    Pursue lifestyle habits that are known to slow aging

o    Pursue activities that are known to slow down, reduce the probabilities of or prevent the major diseases and deteriorative processes of aging.

o    Take supplements or pursue activities that might possibly affect the basic program of aging, so as to slow it down or even conceivably stop or reverse it. 

I will comment on these only briefly here since I have discussed each extensively elsewhere. 

o    Avoid causes of accelerated aging 

This includes such things as avoiding excess stress, exposure to radiation and toxic chemicals, smoking, unnecessary exposure to diseases, living in a smog-filled city and eating too much meat. 

o    Pursue lifestyle habits that are known to slow aging 

This includes exercising regularly, getting adequate sleep, eating healthy diets, keeping mentally challenged and also includes having an even temperament, enjoying an active social life, living with a mate and even having an active sex life.    Regarding these first two strategies, for a more complete list please see The Anti-aging lifestyle Regimen section of my treatise which contains numerous “conventional wisdom” suggestions for keeping yourself young.  Also, a great many past blog entries are relevant such as Recent research on the Mediterranean diet, and Mental exercise and dementia in the news again.  Some of the food suggestions are for things I really like.  For example see the blog entries Health and longevity benefits of dark chocolate and Blueberries and health.  These everyday-life suggestions are not just based on folk wisdom.  They are backed up my many large-population studies.  What you do and what you eat constantly reprograms your genes and affects your epigenome.  See my blog post Who is doing gene reprogramming?   

o    Pursue activities that are known to slow down, reduce the probabilities of or prevent the major diseases and deteriorative processes of aging.

An example is taking antioxidant supplements when confronted with a necessity for having an extensive medical radiological exam.  See the blog entry Medical radiation risk – you can do something about it. Many of the lifestyle suggestions mentioned above have a similar effect.  In the blog entry Nrf2 and cancer chemoprevention by phytochemicals, I point to research reports looking at mechanisms through which food substances rich in phytochemicals (e.g. coffee, chocolate, turmeric, olive oil, broccoli, red hot peppers, green tea, garlic, blueberries, rosemary, oregano, and sage) are cancer-preventative. Also, the taking of many dietary supplements such as those found in my anti-aging Supplement regimen falls in this category.  For example, curcumin, resveratrol, lycopene, olive leaf extract and ashwagandha are among the substances found in the Susceptibility to Cancer Firewall.   Omega-3 oils, resveratrol, curcumin, chromium piclonate, L-theanine, quercetin, Vitamin A, and green tea extract are among the supplements in the Susceptibility to Cardiovascular Disease Firewall.   Complete lists of the supplements in the firewalls for each of the 14 theories of aging are contained in the treatise. 

o    Take supplements or pursue activities that might possibly affect the basic program of aging, so as to slow it down or even conceivably stop or reverse parts of it. 

Here we are dealing with the frontiers of science and only a few things are known now that that might work above and beyond normal lifestyle interventions and taking “the usual” supplements.  As already listed in my treatise,  I see the following as possibly able to contribute to extraordinary longevity, listed in order of increasing sophistication: 

–         Use of combinations of green tea, curcumin, chocolate, ashwagandha, and other phyto-substances for their powerful cancer-preventative effects and cardiovascular benefits that operate through genetic mechanisms.

–         Use of r-alpha lipoic acid and acetyl-l-carnitine to address cell mitochondrial longevity and inhibit unwanted cell apoptosis (self-destruction).

–         Use of resveratrol or resveratrol homologs to activate the SIRT1 and FOXO3 “longevity” genetic pathway, the pathway known to confer life extension due to calorie restriction.

–         Use of astragaloside IV or cycloastragenol to activate telomerase expression in stem and progenitor cells as well as regular body cells.  The purpose is to enhance the life spans of these cells, to enhance the ability of somatic stem cells to divide and differentiate to renew regular body cells, to thereby slow epigenomic aging, and to confer longevity to body organs and systems. My readers will find many blog entries related to telomeres and telomerase.

I don’t know how much additional average longevity taking these supplements will confer.  We base our faith in these substances on molecular biology studies, on studies of gene activation pathways, on studies of the life spans and health of small animals, and on studies of disease processes.  It is far too early to see studies of the impacts of taking these substances in large human populations over periods of years.I have a great deal of faith that as time progresses we will see more and more potentially powerful interventions against aging based on emerging discoveries in molecular biology, stem cell biology and genomics.  I write this blog because I want to be there to report them.