AGINGSCIENCES™ – Anti-Aging Firewalls™

In yesterday’s post I proposed Giuliano’s Law of Anti Aging:

·        Starting now, every seven years will see the emergence of practical age-extension interventions (ones that have a potential of leading to extraordinary longevity) that double the power of the interventions available at the start of the 7 year period.  That is, on an average basis, the practical anti-aging interventions available at the end of a seven-year period will enable twice the number of years of life extension than did the interventions available at the start of the period.  Life extension is measured in years of life expectancy beyond those actuarially predicted for a given population. 

I then went on to calculate my longevity prospects in a quick-and-dirty manner to establish a point: Assuming the law is valid, with each additional year I manage to keep living in good health, if I keep up my anti-aging firewalls program and keep improving that program to reflect ongoing research, my probability of living another year in good health goes up instead of down despite my advancing chronological age.  My purpose here is to do the calculations a bit more carefully to establish the same point.  I consider three cases:

Case 1:  I discontinue my anti-aging firewalls program and go about living a normal life.

Although I am chronologically 79 I estimate that my physiological age is 72, reflecting the fact that I have been pursuing an anti-aging program for over a dozen years now and reflecting other factors such as appearance, relative health, energy, activity levels, etc.  Looking at the actuarial tables for age 72 this means my current life expectancy looking forward is 12 more years which would bring me to a chronological age of 91.  Of course this does not necessarily mean that I would live that long.  In the coming year I would face the probability of death from all causes that a 72 year-old would face.  I could actually live more or less than that.  If I managed to live 7 more years to chronological age of 86, at that time my life expectancy would be that of a 79 year-old, or 8 years looking forward.

Case 2: I continue pursuing my existing anti-aging firewall program keeping it exactly as it is now.

In this case my current life expectancy is the same 12 years as above from the actuarial table, plus another 7 years from pursuing the firewall program or a total of 19 years, which would bring me to a chronological age of 98.  If I managed to live to a chronological age of 86, I would not perceptively age from my current physiological age according to my estimation.  Every year I would face some probability of death from all causes, but a smaller probability than that an average 72 year-old faces because of the protective effects of the firewalls against many common diseases of aging.  The situation would be the same for the next 7-year period, etc.  Not so bad, and likely to get me to or beyond 100.  The same point I made in yesterday’s blog entry.

Case 3: I continue to follow all the relevant threads of anti-aging research, to update the Anti-Aging Firewalls Treatise weekly or more as I have been doing, and periodically update the firewalls and firewall program to reflect this emerging new knowledge.  Further, I incorporate new science-based anti-aging substances and procedures into the firewall program as they become available.

This is the most interesting case, the one where Giuliano’s law becomes relevant.  Right now my life expectancy would be the same as in Case 2.  But consider the situation 7 years from now assuming I am still alive then.  By then assuming Giuliano’s law, the anti-aging firewall program will have twice the efficacy of the program I am pursuing today.  Assuming the efficacy has increased somewhat uniformly over the 7 year period, my physiological age will have retreated somewhat, say 3 years to age 69.  My life expectancy then would be 14 years from the actuarial table plus another 14 years due to the firewall program or a total of 28 years.  So, from a chronological perspective at age 86 my life expectancy would be to live to age 114.  And at chronological age 86 I would still face a probability of death from all causes, but a far smaller probability than an average 69 year-old faces, again because of the protective effects of the firewalls.  Let’s jump out one more 7-year increment to chronological age 93.  By then the firewall program should have 4 times the efficacy of today’s program.  My physiological age should have retreated at least 15 more years back to 54 years of age.  My life expectancy would be 26 years from the actuarial table plus 28 years from the firewall program or a total of 53 years bringing me to chronological age 146. At chronological age 93 I would still face some probability of death from all causes, but a much smaller probability than an average 54 year-old would face. The projection will be that I will break the 122 year human age barrier.  Assuming of course I am not hit by lightening, run over by a taxi or hit by a speedboat  on one of my long swims out in Lake Winnipausakee.

The core assumptions of these scenarios are: 1. My physiological age is 7 years less than my chronological or actuarial age today because of my past anti-aging program participation, 2.  Today’s anti-aging firewalls program will add an average of 7 years to the life of a 79 year-old average male, and 3. Incorporating new knowledge as it is discovered, the life-extending efficacy of the firewalls program can be expected to approximately double every 7 year period (Giuliano’s Law).  Assumptions 1 and 2 are based both on theory and on my subjective sense of looking, acting, feeling and having health patterns of a considerably younger person, conservatively one 7 years younger.  I assume that the retardation of physiological aging due to having been on the anti-aging firewalls program is permanent, in my epigenome.  That is, if I stop the program I won’t lose those 7 years of youth in a few days.   I will provide an argument justifying Assumption 3, Giuliano’s Law, in a later blog post. The ultimate validity of these assumptions will be proven only over a long period of time.   I think I can wait.

What is the prospect of a healthy disease-free adult breaking through the existing 122 year human age limit and going on to live to 150, 200 or 300 years by constantly follows the latest and best anti-aging program?  This is a matter of speculation and speculation on this topic is what I share here. I, for one, expect to break through the limit.

First of all, let me state my opinion on the current stage of anti-aging knowledge and interventions.  These are laid out in detail in my Anti-Aging Firewalls Treatise.  My best guess (and it is only a guess) is, that if you are less than 80 years old, in excellent health, physical and mental condition, and seriously following the lifestyle and supplement firewalls as they are now laid out now, March 26, 2009, you will have a good shot at living to 100 years, perhaps even beyond that point.  Of course time of death will be a stochastic variable depending on numerous personal and environmental factors.  The effects of taking some of the supplements like resveratrol, the alpha lipoic acid–acytl-l-carnitine combination and astragaloside IV will not be known for decades and could possibly buy you a number of additional years. 

Second, I believe that if you carefully follow research related to aging over the coming years and simultaneously evolve your personal anti-aging firewalls to reflect new research findings as they emerge, you will have a real possibility to go on living and transcend the 122-year age limit and keep living healthily.  And, after that, you can continue to keep living healthily for perhaps hundreds of years.  This assumes, of course, a context of a healthy and safe society.

Let me put this in very personal terms. My anti-aging supplement regimen is considerably more sophisticated now at age 79 than it was three years ago and I am observing anti-aging lifestyle protocols like regular exercise more rigorously.  I look the same in photos taken then and now.  I feel as good and have comparable physical, mental and sexual energy.  I might even have a bit more hair on the top of my head, energy and mental acuity.  In other words, I don’t think I have aged much during that time.  But I have evolved and focused my anti-aging defenses significantly.  What I know about aging, its causes and possible anti-aging interventions has grown enormously during those 3 years.   How about the coming three years?  I seem to be able to keep going without slowing doing what I am doing now, assuming I am not hit by a bus or killed in a car accident.  But according to all indications the progress in anti-aging research in the coming 3 years should be much greater than that in the last 3 years. And it will continue to accelerate thereafter.   I am talking about all the kinds of research that shed light on aging, whether that research is motivated by a desire to find a cure for cancer, AIDS or other diseases or by a desire to comprehend cell-cycle topics like apoptosis or cell-cycle arrest better or by a desire to characterize DNA methylation patterns in the human epigenome.  And along with that progress I expect will be identification of ever-more sophisticated practical science-based anti-aging interventions which I will adopt as soon as they are available.  That is the way it has been.  That is the way it will be even more.

In fact I suggest Giuliano’s Law of Anti-Aging, a counterpart to Moore’s law that has characterized the growth in cost-effectiveness of microprocessors since the 1960s:

·        Starting now, every seven years will see the emergence of practical age-extension interventions (ones that have a potential of leading to extraordinary longevity) that double the power of the interventions available at the start of the 7 year period.  That is, on an average basis, the practical anti-aging interventions available at the end of a seven-year period will enable twice the number of years of life extension than did the interventions available at the start of the period.  Life extension is measured in years of life expectancy beyond those actuarially predicted for a given population.. 

Of course, validation of this law will take many decades.  Objective measurements relating anti-aging interventions to extraordinary longevity are yet to be established.

So, for example, if I  assume that today’s anti-aging firewalls confer an average of only 7 years of life expectancy beyond the normal actuarial projection for me, a 79 year-old, then in 2016 I will have 14 years of additional life expectancy beyond the actuarial projection for my age at that time, 86.  The 2004  actuarial table for adult males gives me 8.11 additional years now.  So if I assume 7 additional years due to my anti-aging regimen I now have 15 years of life expectancy to play with, e.g I can expect to live till 94 (which I think is far too low given that my mother lived to 93 without anti-aging interventions).  According to Giuliano’s law, in 2016 I will have the actuarial expectancy for that age, 5.1 years, plus a number of years due to the anti-aging interventions available then.  That number will be twice the 2009 number for 79 year old or 14 years.  Why still 79 instead of 86?  Because I have adjusted my 2016 chronicle age downward to reflect my firewall-adjusted age which remains at 79.   So my adjusted life expectancy will have gone up from 15 years to 19 years by the end of the 7 year period.  By 2023 my life expectancy will have gone up to 31 years. I therefore suspect that with each additional year I manage to keep living in good health, if I keep up my anti-aging research program my probability of living another year in good health goes up instead of down despite my advancing chronicle age.  If you are significantly younger than me, your odds of breaking the 122 age limit barrier are much better.

The first fantasy:  In the Hollywood movie, late at night in her lab the young attractive researcher discovers how to activate “The Longevity Gene,” making human life spans of 200 years possible.  Then her “secret” gets stolen by bad guys and she sets out to get it back.  And the story goes on from there.  In real life the scientific situation is nowhere so simple.  There are hundreds of genes that have something or the other to do with longevity and dozens of complex proteomic signaling pathways that weave them and other genes together. There is no single known master longevity gene, and in fact such a gene might not exist.  So, what is known about “longevity genes?”  A couple of recent studies provides clues:

For one thing, there appears to be a remarkable similarity of “longevity” genes across a wide spectrum of species ranging from yeast to worms to flies to humans.  That appears to be a conclusion revealed by a proteomics study done by the Buck Institute for Age Research based on a “longevity protein network” developed at Prolexys Pharmaceuticals in Salt Lake City, UT. The longevity network looks at 3,271 interactions among 2,338 proteins that impact on life span in yeast, nematode worms or flies.   It also looks at equivalent human versions of 175 of these proteins  and 2,163 additional human proteins that interact with those proteins. The longevity protein network was derived from the Prolexys human interactome database which contains over 120,000 non-redundant interactions among human proteins – the largest of its kind in the world.

“Researchers found that there is a complex web of interactions among the human equivalents of the many longevity genes found in simple animals. The results revealed a ‘surprisingly close relationship between aging processes in humans and simpler organisms.’”  This is an interesting result given the dramatically different life spans involved and the fact that every species has its own typical life span.  Fruit flies, drosophila melanogaster, normally live 7-8 days.  Humans normally live 3,600 times as long.  It appears that many genes regulating aging have been conserved during the process of evolution over more than a billion years.  That result is confirmed by another study done at the University of Wisconsin that identified 25 longevity genes shared by single-celled budding yeast and the roundworm C. elegans.

I believe the result lends credence to  the Programmed genetic changes theory of aging.  Every species has its own program.  And the program evolves as the species evolves.  But where is the program?  It may not be in the genes themselves but in large part in the epigenome, in inherited patterns of DNA methylation and histone acetylation.  We may not be able to change our human genes so easily, but we can certainly affect the epigenome and do so unwittingly every day.  So here is a more sophisticated fantasy: we figure out ways to modify our epigenome so we can live longer.  For example, suppose we wanted to control P53 apoptotic overactivity leading to cell death or senescence.  Suppose we could find a way for reducing activation of P53, say by activating SIRT1 by resveratrol which in turn deacetylates P53.  Not completely a fantasy(ref), perhaps this is a minor update patch to the epigenomic longevity program, one that might prove to be of practical value. 

A recent Finish study evaluated the effect of frequency of sexual intercourse on risk of subsequent erectile dysfunction.  The study was based on written interview data.  A sample consisting of 989 men aged 55 to 75 years (mean 59.2 years) was followed over a 5 year period.  All men were free of erectile dysfunction at study baseline.  The major finding was that the risk of erectile dysfunction was inversely related to the frequency of intercourse and that regular intercourse protects against the development of erectile dysfunction in men in this age range.  Men reporting intercourse less than once per week at baseline had more than twice the incidence of erectile dysfunction compared with those reporting intercourse at least once per week, that is 79 versus 33.  This is yet another example of use it or lose it when body capabilities of older people are concerned.

Graying hair is a sure-fire sign of aging.  But what is going on?  Actually, the hair is being bleached.  Recently-reported research indicates that graying with age is due to a buildup of hydrogen peroxide in human scalp hair shafts – yes the same stuff used to bleach hair.  The peroxide blocks synthesis of our hair’s natural pigment, melanin.  The buildup of hydrogen peroxide is caused by a reduction of an enzyme that converts hydrogen peroxide into water and oxygen, and the graying is compounded by low levels of methionine sulfoxide reducase (MSR) A and B, enzymes that repair hair follicles.  Further, these events disrupt the formation of tyrosinase, a key enzyme involved in the production of melanin.  

What can be done about all this to bring back naturally-colored hair?  That is unclear for now but there are hints.  It appears that a key step in the sequence of hair-bleaching events, oxidation of methionine sulfoxide, can be blocked in-vitro by L-methionine.  Methionine is an amino acid that can be found in sesame seeds, Brazil nuts, fish, meats, and certain plant seeds.  L-methionine is also readily available as a dietary supplement.  Taurine, an amino acid derivative from L-methionine and cysteine metabolism, and also available a dietary supplement, also seems to have a protective effect on human hair follicles in-vitro(ref).  However, so far I have seen no research evidence that dietary L-methionine or taurine can have any impact on human hair color or density.

We as people are very different from each other.  And a medicine that may work well on one person may not work well on another or even poison him.  The dream of personalized  medicine is that your genetic and epigenetic signature is identified in sufficient detail to indicate your disease susceptibilities and your likely responsiveness to treatment options.  Even further, the signature at any point in time may tell you about diseases you already possess that you do not know about, like silent cancers.  This is where DNA methylation comes in,  a process by means of which sites adjacent to genes on chromosomes (promoter regions) are chemically methylated after a cycle of DNA replication(ref).  The methylation is passed on in the course of cell divisions and through generations of people.  The methylation pattern captures the ancesteral history of the cell that is not in the genes themselves and is unique to every cell.  DNA methylation is thought to be one of the main ways epigenetic information is captured and passed on.  See the Feb 28 post in this blog on Epigenetics, Epigenomics and Aging.  Also, this subject is discussed in yesterday’s post Rebooting cells and longevity.

The DNA methylation profiles of individuals are unique, change with aging, and include valuable clues to disease and treatment progress.  For example, DNA methylation of tumor suppressor genes predicts the relapse risk in acute myeloid leukemia for patients in clinical remission(ref).   So, research groups throughout the world are building databases of DNA methylation epigenomic information, in part to establish methylation markers that are “normal” and other markers that indicate diseases, susceptibility to particular disease conditions and associated information . Epigenomics is a company that is focusing on cancer diagnostics based on looking at DNA methylation.  Its goal is to develop and commercialize easy-to-use diagnostic tests for cancer, tests that can be applied at early stages before symptoms occur.  The tests Epigenomics has under development use readily-available body fluids such as blood or urine and are based on detecting differences in DNA methylation patterns between healthy and sick individuals or between subgroups of patients within disease classifications.  One intent is to identify cancer-specific DNA methylation patterns while a patient’s cancer is in a very early stage and more likely to be curable(ref).  For example, researchers in Epigenomics have identified a region in the Septin9 gene that is methylated in 90% of colorectal cancer tissues.  This methylation is found little or not at all in normal colorectal tissues.  DNA methylation testing is not yet part of regular clinical practice but probably will be starting very soon.  Epigenomics has three products in the development pipeline, one for colorectal cancer screening, one for prostate cancer screening and one for lung cancer screening.

DNA methylation is impacted by aging and impacts on aging(ref).  Methylation in the promoter region of genes is thought generally to be associated with gene silencing.  Longevity-related and health-promoting genes may be turned off in the process of aging due to progressive methylation.  The P66Shc gene for example, associated with longevity in mammals, appears to be silenced through some combination of histone deactylation (resulting in protein folding) and cytosine methylation(ref).  Little is known yet about how to go about DNA demethylation, but demethylation appears to be necessary for epigenetic cell reprogramming(ref).  Also, relatively little is known yet about how DNA methylation plays out in aging, yet alone how to work with DNA methylation in order to stop or reverse aging.  Again, it appears that the more we discover, the more there is that we know we don’t know.

An amazing discovery is still in the process of being made.  Exposing the DNA of many kinds of body cells to just four transcription-factor proteins causes a cell to lose all memory of what it is and does and become what is called an Induced Pluripotent Stem Cell (iPS cell), a cell very much like an embryonic stem (ES) cell.  It appears that an iPS cell, like an ES cell, is capable of progressively differentiating into any cell type, be it heart, skin, nerve, bone or muscle.  In other words the four proteins reboot the cell into embryonic stem-cell type pluripotency.  The entire history of epigenomic information that cell has inherited from its progenitors over the entire life of the animal is simply wiped out.  This includes not only information about what the cell has become (e.g. a brain neuron or a bone or liver cell) but also the history of experiences inherited from its progenitors going back to the inception of the animal.  This history, expressed via methylated DNA can strongly condition the behavior of the cell.  See the Feb 28 post in this blog on Epigenetics, Epigenomics and Aging.  

The proteins are Oct4, Sox2, Klf4, and c-Myc.  Oct4 and Sox2 are transcription factors known to have to do with ES self-renewal and proliferation.  Klf4, and c-Myc are transcription factors known for their roles in cell proliferation, differentiation and survival and regulating gene expression.  This reprogramming effect was at first reported in 2006 and limited to starting with mouse fibroblast cells carrying engineered selection markers(ref,ref).  Later, the effect was demonstrated using a retrovirus to transport the proteins into the nuclii of mouse cells(ref) without a need for engineered cells.  However, the retrovirus could also inject its own DNA into the chromosomes affected, so the process appeared to be unreliable because it could affect the genome of the cell.  More recently, it has been possible to induce pluripotent stem (iPS) cells from mouse fibroblasts and liver cells by using relatively benign nonintegrating adenoviruses(ref).  It appears in several experiments that the four proteins wipe clean all the lifelong DNA epigenetic modifications that normally occur as a stem cell progressively differentiates into being a very specific kind of body cell, like a hair follicle cell.  “DNA methylation, gene expression and chromatin state of such induced reprogrammed stem cells are similar to those of ES cells.”

This discovery is still in process because most experimental work so far has been with mouse cells and it is still not known for sure how completely  similar the behavior of iPS and ES are.  Nobody has been able so far to make a mouse out of an iPS cell, for example. The possible implications for regenerative medicine are immense.  The idea is to remove some cells from a person, say a small tube of blood cells, restore these in the lab to being iPS cells and then use these in lieu of ES cells for organ regeneration in that person.  Because the cells are from the same person, there would be no problem of immune system rejection.  Several issues require resolution before this kind of therapy can be practical, however.  First, the pluripotency and safety of using human iPS cells must be confirmed.  There is a possibility that they could contain genetic remnants of the andovirus vector that could create mischief for example.  Second, it is important to find effective ways for introducing the iPS cells into human organs so they achieve the desired results of organ regeneration.  If ES or iPS are randomly injected into body tissues they are likely to form teratomas, ugly encapsulated structures of varied body tissues including lung, heart, liver or brain tissue, or bone, teeth or hair.  Careful attention has to be paid to signaling structure to assure the ES or iPS make the kind of tissues desired and only that kind.  This is a fundamental issue of organ regeneration via stem cell therapy whether ES or iPS cells are used.  Also I am unclear about another important matter.  What happens to the telomeres in a cell from a mature person when it is converted to an iPS cell?  Do the telomeres stay short reflecting the age of the donor or are they somehow enlongated as they would be in an ES cell?  Does an iPS cell have sufficient expression of telomerase when it differentiates to carry it through the large number of generations required for effective organ renewal?  As far as I know, these are issues still to be researched.

In terms of aging, the four proteins seem to turn the clock back in a cell to ground zero.  That is, all the epigenetic information (DNA methylation) that cell and its parents, grandparents, great-grandparents, etc.  gathered in the process of many rounds of cell differentiation and division and life experience is completely wiped away in the process of it becoming reprogrammed as an iPS cell.  For halting or even reversing human aging we don’t want that to happen to most of the cells in our body; it would turn us into blobs of undifferentiated stem cells.  What we might like, however, is selectively to erase epigenetic information related to programmed aging while retaining epigenetic information related to cell differentiation.  Or, more simply put, we would like selectively to reset our cells to a younger state while keeping the degree of cell differentiation appropriate to that younger state.  See the discussion of the Programmed genetic changes theory of aging in my Anti-Aging Firewalls treatise.  This is a challenge of a quite different order of magnitude than is simple rebooting. 

We can probably expect important new research results related to iPS cells in the coming year, months or even weeks. 

A reported large-scale population study by Scottish researchers indicates that longevity is highly correlated with childhood intelligence quotient, especially for people who grow up in poorer neighborhoods.  A thousand people were followed during a 70-year span.  During a 25 year interval  “— 51 percent of the men and 38 percent of the women in the study died. In simple terms, there was a 17 percent greater chance of death for every 15 points of lower childhood IQ. After adjusting for deprivation and social class, this difference was reduced to 12 percent.  These adjustments separated socioeconomic effects from IQ and explained some, but not all, of the differences associated with lower IQ.”  The reasons for this effect are not clear.  One possibility according to the study authors is that poorer people with lower childhood IQ lead more deprived lives and are more vulnerable to diseases and other causes of death.  Another possibility is that low childhood IQ combined with poverty was correlated with low childhood health in the first place leading to increased mortality.  I suggest a third possibility: that members of the higher IQ group had more willingness, commitment and capability to pay attention to their health and longevity and that this effect transcended socioeconomic class.

The nuclear transcription factor NF-kappaB plays a prominent role in one of the advanced theories of aging, Programmed genetic changes.  Several new pieces of research highlight the mechanisms by means of which this multi-faceted substance impacts on aging and the importance of the anti-aging firewall substances that inhibit the expression of NF-kappaB.  I mention two such studies.

One study has to do with the role of Tumor Necrosis Factor (TNF) activating the expression of NF-kappaB in Muscle Progenitor Cells (MPC).  This study is also relevant to the fourteenth theory of aging, Decline in adult stem cell differentiation.  TNF acts via a number of pathways in a complicated manner including activation of NF-kappaB to produce a variety of effects including induction of apoptosis (cell suicide).  This apoptosis is useful when cancers are concerned but is also potentially destructive of healthy cells. It appears that in MPC cells at least, TNF-alpha activates NF-κappaB more in older animals than in younger ones.  This leads to apoptotic signaling and death of MPC.  The problem is thought to be a decline in age of effective cellular mechanisms for keeping NF-kappaB inactive.  Practically speaking, this appears to support the importance of the thirty-nine anti-aging firewall substances that inhibit the expression of NF-kappaB.

A second study has to do with the role of the sirtuin SIRT6 in regulating the expression of NF-kappaB.  Another member of the sirtuin family, SIRT1, has been extensively studied and even sometimes referred to as a key “longevity gene.” But SIRT6 also seems to play an important role in keeping NF-kappaB expression in its proper place.  SIRT6 works with NFkappa-B to control the activity of genes connected with metabolism, inflammation, immunity and aging. When SIRT6 is in short supply, NFkappa-B becomes hyperactive and turns up activity of aging-linked genes.  “We propose that SIRT6 attenuates NF-kappaB signaling via H3K9 deacetylation at chromatin, and hyperactive NF-kappaB signaling may contribute to premature and normal aging.”  Again, taking the firewall substances that control expression of NFkappa-B may be an effective anti-aging measure.

The third theory of aging covered in my Anti-Aging Firewalls treatise is Mitochondrial DNA Mutation.  Research reported today relates to the relationship of mitochondrial dysfunction to Parkinson’s Disease (PD).  Other new research indicates that taking two substances in the anti-aging firewalls that act on the mitochondria may prove to be a safe and effective strategy for preventing PD. The new research indicates that an inherited form of PD is caused by mutations in the PINK1 gene which is localized to mitochondria. The researchers found that insufficient expression of PINK1 leads to an aberrant calcium overload inside the mitochondria.  The calcium overload in turn results in the production of Reactive Oxygen Species (ROS) that interfere with the ability of the mitochondria to transport sugar needed for energy production.  The result can be injury to and death of dopamine-producing neurons leading to Parkinson’s Disease. 

Since excess mitochondrial ROS are involved, it seems plausible that antioxidants that act in the mitochondria might help prevent PD. We have known for a few years from the pioneering work of  Bruce Ames that a combination of alpha-lipoic acid and actyl l-carnitine and alpha-lipoic acid act together powerfully in such a capacity.  Many studies have confirmed the power of these two anti-aging firewall substances for brain health when taken together.  “Dietary supplementation of young and aged animals increased the proliferation of intact mitochondria and reduced the density of mitochondria associated with vacuoles and lipofuscin.  Feeding old rats ALCAR and LA significantly reduced the number of severely damaged mitochondria (P = 0.02) and increased the number of intact mitochondria (P < 0.001) in the hippocampus.  These results suggest that feeding ALCAR with LA may ameliorate age-associated mitochondrial ultrastructural decay and are consistent with previous studies showing improved brain function. (ref)”  A research report originated in a Chinese university looks more directly at how these two substances might prevent PD:  Combined R-α–lipoic acid and acetyl-L-carnitine exerts efficient preventative effects in a cellular model of Parkinson’s disease.