Professional Documents
Culture Documents
ANTI-AGING NUTRITIONAL
SUPPLEMENTATION
WHAT IF AGING WERE NOT INEVITABLE?
CHARLES FEELGOOD
LINUS FREEMAN
ANGLIQUE HOULBERT
CONTENTS
Since the beginning of time, man has sought to extend his lifespan and pro-
long the energy of youth. Various religions and alchemists have taken up
the mantle, offering the promise of eternal life. But today, it is science-led
anti-ageing nutrition and medicine that is signaling an optimistic future for
human life expectancy. Not so long ago, doctors believed that the principal
factors governing ageing were chronic stomach poisoning and degeneration
of the immune system.
But preventive nutrition and anti-ageing medicine have moved far beyond these common, sim-
plistic explanations, and are beginning to open the door to the real and foreseeable possibility
of longevity way beyond what is currently considered feasible. For now, of course, it remains
just a possibility there are many hurdles to be overcome But certain studies are showing
considerable promise, such as the work of English bio-gerontologist Aubrey de Grey, whose
anti-aging strategy sets him apart from his peers
Until de Grey, only two schools of thought really existed on how to delay ageing:
1 The first consists of slowing down the process whereby damage linked to the bodys
degeneration causes disease, and delaying the point at which disease becomes serious
and ultimately fatal. However, by definition, this is a very short-term strategy since
damage is accumulating all the time and it becomes increasingly difficult to combat
such cumulative damage - especially since that fatal threshold is reached all too soon.
Such limitations have led Aubrey de Grey to adopt a third strategy which he terms
engineering.
Dr Aubrey de Grey
Biogerontologist
n a sense, the engineering method offers anti-aging science a way of bypassing current igno-
rance. Indeed, its sole objective is to enable those who want to, to live long enough to benefit
from the advances science will achieve in a few decades time.
Perhaps its greatest advantage, however, is that without being overly simple, it is the least com-
plex approach. It condenses the question of damage repair into 7 deadly factors.
These are the seven types of damage accumulated over a lifetime which contribute to
aging and eventually become pathogenic.
Buying time
Thus Aubrey de Grey believes not in biological immortality but in bio-technological immorta-
lity taking an engineers approach, and applying a strategy of extensive repair to prevent the
accumulation of damage. Holding back aging in this way would seem possible insofar as it is a
much less complex approach than trying to reverse aging once it has appeared like trying to
keep a boat from sinking once its sprung a leak.
Furthermore, even incomplete repair might be enough to achieve the desired result which
would not be the case with incomplete reversal of aging.
Improvements can thus afford to be modest since it is only a question of prolonging life until
such time as it is possible to truly extend life for longer. Betting on the future in this way may
seem unwise to some but since aging inevitably blights everyones future, why not at least try
it? After all, scientific and technical advances are being made all the time in most technologies.
Aubrey de Grey cites the example of aviation which took centuries to evolve, but once func-
tionality was achieved, progress accelerated rapidly over the last century. The same sort of
chronology applied to IT and infection control amongst many others. So its not unreasonable
to believe that, once treatments capable of extending life expectancy by 30 or 50 years have
been developed for people in their fifties, this same population will be able to benefit, in 30 or
50years time, from more effective repair techniques which are likely to further extend lifespan
by 50 years, etc. This is the philosophy behind the engineering method.
If youre already 100 years old, we wont be able to give you back 30 or 50 years of extra life because you will
already be too weak to withstand treatment which is experimental rather than proven. If youre 80, we wont
be able to do much for you. But if youre 50, it will be rather like jumping off a cliff with a jet-pack on your back
a jetpack that you turn on halfway through your fall. This metaphorical jetpack will slow your descent and
with a bit of luck, youll avoid a nasty crash at the bottom - instead of falling to the ground, youll start to climb
again. In other words, youll begin to rejuvenate biologically and be less prone to age-related diseases. And if
youre aged 30 when you start treatment, you wont even get near the ground
De Grey says quite seriously that he will need an investment of 100 million dollars a year for
around 10 years to achieve rejuvenation in mice and its no secret that he has already succee-
ded in attracting significant funding.
Such rejuvenation would consist of taking a healthy strain of mice, allowing them to live to the
age of 3 with no special diet or medication, and then applying the engineering method, in order
to treble what would normally be their remaining one year of life, taking their life expectancy
to 6 years. With regard to humans, theres a 50% chance of similarly doubling life expectancy in
a 50 year-old, and it is envisaged this could be achieved 15 years after it is successfully realised
in mice.
He concedes that if luck is not in their favour, it could obviously take more than 100 years, but
there is a 50/50 chance it might be achieved in just 15 years!
Dr Aubrey de Grey works in the department of genetics at Britains Cambridge University. The focus
of his work in biogerontology, the study of the bodys aging process, is the development of a genuine
treatment for aging. He has developed a potential repair programme, called Strategies for Engineered
Negligible Senescence (SENS), which divides the problems of aging into seven key types of damage
and identifies detailed approaches for treating each of them. One of the principal aspects of the SENS
approach is its focus on indefinite life extension through maintaining good health, even with imperfect
repair processes; repair only needs to be sufficiently effective to maintain damage below pathogenic
levels. Dr Grey calls this Longevity escape velocity these ideas are described in detail in his book
Ending Aging, published in 2007.
These include a top quality* multivitamin, to provide a daily or even several times daily
dose of all the substances essential for a healthy body and for reducing the risk of cancer. Indeed,
a new study 1 has recently confirmed the benefits of a multivitamin in reducing cancer risk. The
multivitamin complex used in the study comprised all the water- and fat-soluble vitamins, the
main minerals and oligo-elements (magnesium, zinc, selenium, iodine, manganese, chromium,
molybdene, boron) as well as two essential carotenoids lycopene and lutein. These nutrients
References
J . Michael Gaziano, MD, MPH; Howard D. Sesso, ScD, MPH; William G. Christen, ScD; Vadim Bubes, PhD;
Joanne P. Smith, BA; Jean MacFadyen, BA; Miriam Schvartz, MD; JoAnn E. Manson, MD, DrPH; Robert
J.Glynn, ScD; Julie E. Buring, ScD. Multivitamins in the Prevention of Cancer in Men - The Physicians
Health StudyII Randomized Controlled Trial. JAMA.2012;():1-10. doi:10.1001/jama.2012.14641.
The good news is that the arsenal of anti-aging weapons available today is greater than ever
before we already have a number of products, almost all in nutritional supplement form, which
can address this issue. They are available to everyone right now, to help fight the 7 deadly
things identified by Aubrey de Grey and ultimately reverse, not just slow down, the infernal
mechanism which leads first to degeneration, and eventually the grave!
1 Telomerase activators
The identification of these substances represents a major breakthrough. Telomerase enables
production and growth of telomeric DNA. Located at the tips of chromosomes, telomeres enable
cells to reproduce, but when they become too short the cells die. With telomerase activators,
however, cells can hopefully surpass the Hayflick limit and continue to reproduce, enabling us
to avoid one of the most seemingly inescapable mechanisms of aging.
Found in the nucleus of cells, telomeres are the tips of double-stranded DNA. Their purpose is to
protect the genome from losing data when cell division shortens chromosomes. Unfortunately,
telomeres get progressively shorter, particularly when inflammation or stress is present, so that
by the age of 80, our telomeres will be two to three times shorter than at birth.
Indeed, telomeres shorten with each and every cell division and so their replication is always
incomplete. The greater the frequency of cell division, or the more oxidative stress is present,
the more the telomeres shorten. At a particular point, when the telomere reaches a critical size,
the cell becomes senescent. Until now, this has been an inevitable mechanism of aging.
What is telomerase?
Telomerase is a nucleoprotein enzyme which catalyses the production and growth of telomeric
DNA and stimulates the repair of DNA damage.
Telomerases role begins right at the beginning of embryonic development. It is then, when
the rate of cell division is extremely high, that this enzyme is at its busiest. Consisting of protein
and RNA, telomerase continually repairs the chromosome tip during foetal development, thus
maintaining the telomeres integrity.
However, things start to deteriorate as early as birth! Levels of telomerase begin to fall and
continue decreasing until adulthood. From this point, more telomerase becomes available in
sex cells and stem cells, although it has almost disappeared from somatic cells.
That said, the stem cells activate as much telomerase as is necessary for tissue regeneration, but
this last vestige of activity is clearly not enough to prevent the general decline in telomerase at
the end of life, especially when the body is frequently under stress. Indeed, stress results in an
increased requirement for cell renewal and thus a greater number of cell divisions.
As a result, the turnover in telomeres is much faster and aging becomes apparent much ear-
lier. The increase in telomere shortening when telomerase is deficient has been confirmed by a
number of studies. They have all shown that the immediate consequence of this shortening is a
drastic reduction in cell lifespan.
Given that telomerase lengthens telomeres and makes cells virtually immortal, an obvious
question is what is its effect on cancer cells? Or, worse still, could it turn healthy cells into can-
cer cells? We know that a tumour is a proliferation of cells that have become immortal and
are reproducing very actively. A cancer cell is therefore different from a normal cell because of
its immortality. Because of the potentially catastrophic effects of using telomerase to combat
aging, new studies were carried out, the results of which were published in 1999. Happily, they
provided unequivocal evidence that such concerns were groundless. In a publication 1, Dr Woo-
dring Wright confirms that, the addition of telomerase in human cell culture does not cause cells to
develop into cancer cells. It seems that even when human cells are multiplied many, many times
beyond their life expectancy (more than 200) it does not result in cancer cells.
DrWoodring Wright
References
1 I nhibition of human telomerase in immortal human cells leads to progressive telomere shorte-
ning and cell death. Herbert B., A.E. Pitts, S. I. Baker, S. E. Hamilton, W. E. Wright, J. W. Shay, D. R. Corey,
Proc. Natl. Acad. Sci. USA, 1999; (96/25): 14276-14281.
2 DePinho R. A. et al. ,Telomerase activation reverses tissue degeneration in aged telomere-deficient
mice. Nature 469, 102-106, January 2010. Published online 28 November 2010.
A number of molecules studied and used in humans for several years have been clearly shown
to stimulate telomerase, increasing their numbers, and lengthening them appreciably. As a
consequence, they are able to reverse certain aging mechanisms by postponing the cell death
thought to be inevitable after a certain number of divisions. These molecules are likely to be just
the first of a growing list over the coming years.
The two most promising come from a plant that has featured in traditional Chinese medicine for
thousands of years: the dried root of astragalus (Astragalus membranaceus). This plant has been
traditionally used as a tonic and stimulant of the immune system:
it increases the number of stem cells in bone marrow and lymphatic tissue and pro-
motes their development into active immune cells;
it switches immune cells from a resting state to an active one;
it produces immunoglobulins;
it stimulates macrophages;
it activates natural killer cells and T-lymphocytes;
it stimulates endogenous interferon production and maximises its effects against
viral infections;
it increases resistance to the immune-suppressive effects of chemotherapy drugs;
and finally, it stimulates production of interleukin-6 and tumour necrosis factor.
The numerous studies conducted on this plant have highlighted its many exceptional pro-
perties; in addition to immune-stimulant benefits, it also has antioxidant, anti-inflammatory,
anti-fibrotic, and neuro-protective properties, as well as cardio-protective properties, due to its
ability to inhibit the formation of oxidised lipids in the myocardium, increase vasodilation, and
reduce blood clotting. It also has beneficial, cardiotonic effects in angina pectoris.
In addition to the benefits of the whole plant, researchers are particularly interested in its active
compounds to which most of its properties are attributed. A highly complex and costly process
has enabled two active substances to be isolated and concentrated from this plant that have a
similar chemical structure and amazing anti-aging properties:
It is cardioprotective
Studies conducted on astragaloside IV, show that it can:
reverse endothelial dysfunction caused by hyper-aminoacidaemia (presence of
excessive amino acids in the urine), which is strongly associated with cardiovascu-
lar problems;
considerably reduce the severity of heart attacks (as shown in dogs subjected to
coronary ligature in vivo);
improve post-ischaemic cardiac function and reperfusion arrhythmia in rat hearts
in vitro.
Its also worth noting that the cardio-protection afforded by astragaloside IV was accompanied
by a significant increase in coronary flow both in vivo and in vitro 2.
Immunostimulant
Generates more active immune cells, immunoglobulin and macro-
phages;
Activates T lymphocytes and natural killer cells;
Increases production of T and B lymphocytes, and antibodies 3;
Increases stem cells in the spinal cord and encourages their develop-
ment into active immune cells.
Anti-inflammatory
Reduces inflammation of the airways in chronic asthma.
Anti-bacterial
Acts, in vitro, against Shigella dysenteriae, Streptococcus haemolyticus,
Diplococcus pneumoniae and Staphylococcus aureus.
Anti-viral
Inhibits replication of certain viruses;
Produces interferon and maximises its effect against viral infections.
Antioxidant
In vitro, inhibits 40% of lipid peroxidation.
Cardioprotective
Has beneficial effects on congestive heart failure and angina pectoris;
Aids recovery following cardiovascular problems.
Neuroprotective
Improves treatment of neurodegenerative diseases;
Protects dopamine neurons from the degeneration which causes Par-
kinsons disease;
Protects against the toxic effects of chemotherapy.
Antiglycation
Prevents the neuropathic complications of diabetes.
Astragaloside IV is not the only active principle of the astragalus plant. Cycloartane-type sapo-
nins are also important constituents of astragalus root, to which are attributed astragalus
wound-healing properties, one of its uses in traditional medicine.
Saponins are amphipathic glycosides, ie both hydrophilic and lipophilic. Cycloastragenol, tested
in vivo and in humans for several years, seems to be the most powerful of the saponins in terms
of anti-aging treatments.
With this in mind, nutraceutical research has been investigating resveratrol and cycloastragenol
for their ability to improve the function of T cells in vivo, and has evaluated their effects on:
cell proliferation;
telomerase activity levels;
surface marker levels;
cytokine secretion by CD4 and CD8 T lymphocytes.
Research shows that cycloastragenol produced a slight increase in telomerase activity and the
proliferative capacity of T cells CD4 and CD8. The results suggest that these substances can inhi-
bit the appearance of CD4 and CD8 and cell senescence 2. In addition, researchers noted that
the saponin is not cytotoxic for cancer cells, but that it increases proliferation of lymphocytes3.
Just as for astragaloside IV, it is important to check the certificate of analysis when selecting a
cycloastragenol product.
Cycloastragenol is already known across the Atlantic as the main ingredient in TA-65 from Telo-
merase Activation Sciences (TA Sciences), a product taken by thousands of people since its
launch in 2005.
Cycloastragenol thus constitutes a powerful anti-aging weapon that can repair DNA damage
because it:
The chemical structure of cycloastragenol is fairly similar to that of astragaloside IV. However,
its low molecular weight means it crosses the intestinal barrier easily and because it is optimally
absorbed, increased efficacy is achieved at a lower dose. Daily supplementation with cycloas-
tragenol, in combination, or alternating, with astragaloside IV, can help control the aging pro-
cess and naturally extend life expectancy, given that the spectrum of activity of these two sup-
plements is obviously wider when they are combined.
As for astragaloside IV, you could not realistically ingest a sufficient quantity by taking astraga-
lus plant capsules as they only contain a tiny amount. You would need to consume hundreds of
whole plant capsules and tens of 50:1 extract capsules, the most potent available, to obtain the
amount of cycloastragenol shown to be effective.
It is therefore vital to take a concentrated, purified nutritional supplement.
The dose should also be calculated according to age. Cycloastragenols efficacy seems to be
dose-dependent and people with the shortest telomeres who are usually older achieve the
most effective and rapid results with higher doses, 25mg to even 50mg a day. While those in
their thirties can therefore rely on 10mg a day, 70 year-olds should be taking between 25 and
50mg a day.
References
1 A ndrews, W. West, M. Report: Turning on Immortality: The Debate Over Telomerase Activation. Life
Extension Magazine. August 2009.
2 Valenzuela H. F., Fuller T., Edwards J., Finger D., Molgora B., Cycloastragenol extends T cell prolifera-
tion by increasing telomerase activity. J. of Immun. 2009, 182, 90.30.
3 V erotta L., Guerrini M., El-Sebakhy N. A., Assad A. M., Toaima S. M., Radwan M. M., Luo Y. D., PezzutoJ.M.,
Cycloartane and oleanane saponins from egyptian astragalus spp. as modulators of lymphocyte
proliferation. Planta Med. 2002 Nov.; 68 (11): 986-94.
Promising new studies continue to confirm the benefits of some other nutrients and phytonu-
trients in maintaining telomeres.
To recap, telomeres are the fine protective tips at the end of our chromosomes. Every time our
cells divide, DNA has to replicate but with each cell division, telomeres get shorter and the lifes-
pan of the cell decreases. As mentioned, this telomere shortening is directly linked to cellular
aging and the development of a host of age-related diseases.
Telomerase is an enzyme that can lengthen the shortest telomeres. Recent studies show that
telomerase significantly affects the shortest telomeres rather than average telomere length. In
fact it is the percentage of short telomeres that is the best marker of senescence and even
mortality. Cycloastragenol and astragaloside IV have been shown to stimulate telomerase and
lengthen the shortest telomeres representing a massive advance though they have little or
no effect on average telomere length. It is therefore strongly recommended that these subs-
tances be combined with other nutrients and phytonutrients to complement and boost their
action.
Researchers have identified a number of substances likely to help mitigate this telomere shorte-
ning, in some cases significantly so, with genuine, consistent and confirmed effects.
This is a rare and stable form of vitamin C which is able to penetrate into cells. In vitro stu-
dies have shown that introducing it into human vascular endothelial cells prevents up to
62% of telomere shortening, via suppression of intracellular oxidative stress, whereas the
natural form of vitamin C, ascorbic acid, has no effect. In addition, this form of vitaminC
prevents the cell from widening, a valuable marker of cell senescence.
Extract of the fruit of this plant, standardised to 30% tannins, has demonstrated cyto-pro-
tective effects against oxidative stress (particularly UVB-associated oxidative damage), as
well as inhibitory effects on cell aging, in a study conducted at the College of Pharmacy
of Chungnam University, Korea. Compared with non-treated controls, telomere shorte-
ning was 45% lower.
Tocomax, a standardised extract of palm fruit oil, provides d-gamma tocotrienols - vita-
min E isomers that boost the action of tocopherols. An in vitro study has demonstrated
the protective effect of d-gamma tocotrienol against oxidative stress and its potential
to produce significant increases in telomere length by modulating telomerase activity.
In this study, cells were exposed for 24 hours to gamma tocotrienol, before and/or after
two hour exposure to hydrogen peroxide. At the doses used in this study, the telomere
length of treated cells was over 16% longer than controls.
Marine omega-3
A team led by Professor Jan Kiecolt-Glaser of Ohio University and Elizabeth Blackburn, a
pioneer in the field of telomere research, conducted a study involving 106 overweight
adults. Each was assigned to one of three groups: the first received 2.5g/day of omega-3,
the second 1.25g/day and the third was blindly given a placebo.
The study showed that after four months, levels of F-isoprostanes, a marker of oxidative
stress, were markedly lower in the two groups supplemented with omega-3 fatty acids.
Supplementation with marine omega-3 over a four-month period notably increased ave-
rage telomere length, thus affecting one of the key processes of cellular aging. These
results confirm those of an earlier study, published in 2010, which showed that high cir-
culating levels of omega-3 were able to slow down cellular aging in coronary patients.
References
J anice K. Kiecolt-Glaser, Elissa S. Epel, Martha A. Belury, Rebecca Andridge, Jue Lin, Ronald Glaser,
William B. Malarkey, Beom Seuk Hwang, Elizabeth Blackburn. Omega-3 fatty acids, oxidative stress,
and leukocyte telomere length: a randomized controlled trial. Brain, Behavior, and Immunity. Avai-
lable online 23September 2012, ISSN 0889-1591, 10.1016/j.bbi.2012.09.004.
Mitochondria are the cells powerhouses they enable cells to function at full capacity. A young
persons cells contain a great many mitochondria between 2,000 and 2,500 per cell but as
we age, levels of mitochondria decrease and those that remain become less effective and pro-
duce more waste products. The result is a huge loss of energy, which is implicated in the majo-
rity of age-related degenerative diseases: physical and cognitive problems, accelerated cell
breakdown, cardiovascular problems.
This mitochondrial dysfunction has been
definitively linked to almost all deadly
diseases of aging, Alzheimers disease, type2
diabetes, heart failure, etc. Scientists have
clearly noted greater evidence of mitochon-
drial damage in the brain cells of men aged
70+ compared with those of 40 year-olds.
The health and function of mitochondria, the
cells powerhouses, are now considered so
important that many scientists believe that
mitochondrial longevity is synonymous
with aging body longevity.
PQQ is ubiquitous in the natural world, particularly in all plant species. The fact that it is found
in cosmic dust has led some experts to hypothesize that PQQ played a central role in the evo-
lution of life on Earth itself 2. It is a powerful growth factor in plants, bacteria and higher forms
of life 5, 6. Neither humans nor the bacteria that colonise the human digestive tract are able to
synthesise PQQ 3.
Studies show that when animals are deprived of dietary PQQ, they suffer stunted growth, impai-
red immunity, compromised reproductive capability, decreased numbers of mitochondria in
tissue, lower rates of conception, and lower numbers of offspring and survival rates in young
animals 7, 8, 9. Unsurprisingly, reintroducing PQQ to their diet reversed these effects, restored
systemic function and simultaneously increased mitochondria and energy efficiency.
These findings have led researchers to include PQQ among those nutrients classed as essential4.
Whether it is classified as a new vitamin or a new coenzyme matters little in terms of its anti-
aging efficacy.
The most extraordinary finding relating to PQQ came in 2010, when researchers at a Californian
university noted that it not only protected mitochondria from oxidative damage but actually
stimulated their growth 1. In other words, it promotes generation of new mitochondria in senes-
cent cells.
Multiple applications
PQQ thus powerfully combats mitochondrial dysfunction and degeneration and can generate
new mitochondria in aging cells. In addition, however, it protects the brain, heart and muscles
from aging and degeneration.
Studies have shown that PQQ prevents the development of alpha-synuclein, a protein linked
to Parkinsons disease 21 and also protects nerve cells from oxidative damage by beta-amyloid
protein, associated with Alzheimers disease 22.
One study conducted in 2010 showed that PQQ could prevent the formation of beta-amyloid
molecular structures 23.
PQQ has also demonstrated ability to protect memory and cognition both in animals and
elderly humans 24, 25. The fact that it stimulates production and release of nerve growth factor
in cells and neurons 26 may partly explain why PQQ supplementation in elderly rats resulted in
a marked improvement in their memory function 24.
A recent double-blind, placebo-controlled study showed that a daily dose of 10-20mg of PQQ
significantly improved short term memory as well as concentration in young adults, compared
with a control group.
In another double blind, placebo-controlled study conducted in Japan in 2007, administering
20 mg PQQ supplementation a day to middle-aged volunteers produced improvements in
cognitive function 25 (the performance of the supplemented group was twice that of the pla-
cebo group), especially when subjects also took 300 mg/day of CoQ10. The study therefore
suggests a synergistic relationship between PQQ and coenzyme Q10 which enhanced perfor-
mance in memory tests. This combination can therefore be used to improve mental aptitude
and quality of life and to help slow down or prevent cognitive decline.
R-alpha lipoic acid is the most biologically active form of alpha-lipoic acid, naturally produced
by the body. It is the most important mitochondrial antioxidant. Numerous studies have looked
at it in combination with acetyl-L-carnitine to establish the synergistic effects of these two com-
ponents on mitochondrial function. The benefits observed in these studies include improve-
In his interview in the May 2010 issue of NutraNews, Dr Ames was clear: When we gave R-lipoic
acid combined with acetyl-L-carnitine, all the functions we were examining that had declined
with age were restored. The mitochondria produced fewer oxidants and the mitochondrial
membrane potential improved. Dr Ames demonstrated the involvement of this mitochon-
drial dysfunction in degenerative diseases, including cancer and neurological decline. He also
showed that combined administration of acetyl L-carnitine and R-lipoic acid enabled the effects
of calorie restriction to be mimicked and optimal mitochondrial function to be restored both in
the heart and brain.
It is therefore a good idea to complement the action of PQQ - the only nutrient capable of
generating new mitochondria - with these two nutrients, the most scientifically-supported for
maximising the function of existing mitochondria.
with CoQ10
In addition, it now appears that combining PQQ with coenzyme Q10 significantly enhances the
benefits of the former. This is not altogether surprising, given the key role played by CoQ10 as
a mitochondrial fuel for promoting cellular respiration and increasing production of adenosine
triphosphate (ATP).
Recent studies have highlighted improved cardiovascular and cognitive performance when
these two nutrients are taken in combination, as opposed to separately. This is not unusual in
that the heart and brain are the two organs that consume by far the most energy.
A Japanese study conducted in 2007 showed that PQQ, taken in daily doses of 20mg, improved
memory, attention and cognitive function. The performance of the PQQ-supplemented group
was twice that of the placebo group. Combining PQQ with 300mg of COQ10 further enhanced
performance in memory tests. Mental aptitude and quality of life can therefore be improved
in elderly people, and this combination can help prevent age-associated decline in cognitive
function.
Soluble in water, PQQ does not accumulate in the body and does not lead to intolerance, even
at high doses. It can therefore be consumed by everyone who wishes to control one of the
major mechanisms of aging.
PQQ adds to the arsenal of recognised anti-aging weapons and can be used simultaneously,
or, as we have seen, alternated with telomerase activators (cycloastragenol, astragaloside IV),
as well as with the calorie restriction mimetics (resveratrol, oxaloacetate) covered in the next
chapter.
The work of Dr Roy Walford has shown that severe calorie restriction, but
not malnutrition, is the safest way of significantly extending lifespan - by
between 20% and 30% in most mammals and almost 100% in certain spe-
cies. Walfords research has been partly supported even in humans, by the
findings of the Biosphere II experiment in which he personally participated
The researchers showed that it is possible to modify the messages transmitted by the genes to
the body. This process of gene expression occurs when an internal or external stimulus activates
or inhibits certain genes (protective or harmful).
Researchers have identified a family of genes called sirtuins, which are present in the tissues of
almost all life forms from monocellular organisms to plants and mammals. An increasing body
of evidence suggests that sirtuins regulate energy metabolism, endocrine signalling and cer-
tain stress responses. Sirtuins are also activated by a wide range of signals in response to stress,
such as during periods of famine or calorie restriction, suggesting that they play a key role in the
physiology of mammals.
Sirtuins are also known to act as guardian genes, protecting cells and increasing their survival
rates. Sirtuins include a group of enzymes called deacetylases which slow down aging by affec-
ting a number of cell mechanisms such as DNA repair, resistance to oxidative stress or cell death.
Sirtuins action begins when external signals indicate a deterioration in environmental condi-
tions. Longevity genes are then stimulated to induce defensive changes at a cellular level, such
as slowing down metabolism and increasing cell respiration in order to help the body adapt to
a more effective programme of survival.
It has been shown that human sirtuin, SIRT1 for example, suppresses the enzyme P53, which is
usually involved in inhibiting tumour growth and promoting cell death (apoptosis). By suppres-
sing P53 activity, SIRT1 prevents the cycle of apoptosis and premature aging triggered when
cell DNA is damaged, thus giving the cells sufficient time to repair all the damage and prevent
unnecessary cell death.
It has also been shown that a second sirtuin, SIRT2, present in yeast, is activated when subjec-
ted to stress. It increases DNA stability and accelerates cell repair, while increasing total cell
lifespan4, 5.
In general, sirtuin activation increases sensitivity to insulin and lipolysis, decreases inflamma-
tion and plays a preventive role in neurodegenerative diseases and carcinogenesis. One study
showed that transgenic mice overexpressing SIRT1 presented the same phenotype as calorie-
restricted mice.
Among those identified, the two main substances are resveratrol and oxaloacetate which can
be combined with complementary substances such as quercetin and pterostilbene which add
to the effects of calorie restriction by inhibiting systemic inflammation, boosting mitochondrial
health and protecting brain and heart tissue from age-related deterioration.
Resveratrol is a stilbene from the phytoalexin family. Its also a polyphenolic compound, from
the flavonoid group, and thus a powerful antioxidant. Many plants, particularly grapevines, pro-
duce this protective substance in response to pathogenic insults resulting from UV and ozone
exposure. Its worth noting here that resveratrol is concentrated in the leaves of the grapevine,
the grape skin and pips, and that its found in the fermentation of red wine but not in white.
It was Japanese scientists who originally began to take an interest in this substance in the 1980s
when a traditional remedy, Kojo-Kon, attracted their attention. This medicine contained a plant
called Polygonum cuspidatum, which was used to treat a range of disorders including allergies,
skin inflammation and hyperlipidaemia. They succeeded in isolating the plants active principle,
resveratrol 1. From 1985 onwards, studies increased and much more became known about the
metabolic properties of resveratrol.
Studies on leucocytes in rats demonstrated its ability to inhibit production of eicosanoids. These
include prostaglandins, thromboxanes and leukotrienes which are involved in inflammatory
reactions and platelet aggregation.
SIRT 1
Cell death
Inflammation
Cell repair
Lipolysis
Resistance to carcinogenesis
oxidative stress
Prevention of
neurodegenerative conditions
Free radicals
Increase
in lifespan
Conversely, resveratrol and some other antioxidants can stimulate production of prostacyclin, a
substance that prevents blood clot formation, keeps the arteries dilated and promotes healthy
endothelial walls. Prostacyclin also happens to be synthesised by healthy endothelial walls due
to an enzyme called prostacyclin synthase. Unfortunately, the work of this enzyme can be almost
wiped out by certain free radicals, particularly lipid peroxides or hydroperoxides. Production of
prostacyclin necessarily entails the reduction of hydroperoxides and lipid peroxidation. This is
where resveratrol comes into play, acting synergistically with certain other bioflavonoids, vita-
mins C and E and selenium. These nutrients act synergistically to reduce platelet aggregation,
maximise prostacyclin productionand minimise production of thromboxane and free radicals.
Finally, resveratrol also restores adequate nitric oxide levels. Nitric oxide is absolutely pivotal to
a healthy cardiovascular system, as it enables dilation of arteries and thus good circulation. A
high-fat diet reduces nitric oxide levels by a third. So here too, we can see how resveratrol sup-
plementation can prove extremely beneficial in reversing this unwelcome tendency.
Cancer is perhaps the most promising area of resveratrol research, with an increasing number
of studies leading to a deeper understanding of this amazing substance.
Resveratrol is quite simply the most effective natural substance at stopping various stages of
the development of all types of cancer initiation, promotion and progression.
Resveratrol affects cancer both by blocking oestrogens and androgens as well as through gene
modulation; it can thus combat a number of cancers, in a preventive as well as curative capa-
city. Several recent studies show that resveratrol kills cancer cells whether or not they have the
tumour suppressor gene 4, or whether or not they are oestrogen receptor-positive or negative.
One of resveratrols mechanisms has been identified with the discovery that the body converts
this polyphenol into an anti-cancer agent capable of targeting and killing cancer cells. In par-
ticular, it showed how the enzyme cytochrome P450 found in various tumours metabo-
lises resveratrol into a phyto-oestrogen called piceatannol, which has anti-cancer properties.
The death of cancer cells triggered by piceatannol, and thus resveratrol, causes absolutely no
damage to normal cells 5.
In addition, it seems that resveratrol can also boost certain types of chemotherapy. Researchers
at the University of Notre-Dame discovered that resveratrol maximises the effects of vitamin D.
Vitamin D3 has the particular ability of being converted into a steroid that inhibits growth of
breast cancer cells.
In a very detailed study, Austrian scientists have demonstrated that resveratrol prevents cancer
cells from metastasizing to bone.
However, the best results have been recorded for cancers of the pancreas, breast and kidneys.
Results for colon and prostate cancer were also encouraging but on a smaller scale.
Another of resveratrols properties is that of reducing the harmful effects of the omega-6 fatty
acid, linoleic acid, an ingredient prominent in the Western diet that promotes the growth of can-
cer cells. Linoleic acid is actually converted into arachidonic acid, which in turn is converted into
hormone-like substances (such as prostaglandin E2 or leukotriene B4) that stimulate inflamma-
tory processes, and as result, the growth of cancer cells. Tests on rodents show the Western diet
alone is sufficient to cause colon cancer.
Japanese researchers have confirmed that resveratrol - at a dose easily available from supple-
mentation, blocked the growth-promoting effect of linoleic acid and inhibited the growth of
breast cancer cells.
As a first-class antioxidant, its no surprise that resveratrol protects the brain from free radical
attack. But it also plays a role in the treatment of some quite specific diseases:
Cerebral congestion, which occurs when blood flow to the brain is impeded, depriving it
of oxygen and nutrients. Neurotransmitters are released that allow calcium to penetrate
neurons, thus flooding the brain with free radicals which can lead to cell death. Another
example is Alzheimers disease which is stimulated by oxidative damage to brain cells.
Thus, in a similar way to calorie restriction, resveratrol activates longevity genes called sirtuins.
In order to test the power of resveratrol to activate sirtuins in humans, the researchers chose
yeast as being most closely-related to humans. They hypothesised that if resveratrol proved
able to modify the newly-identified target-genes to trigger sirtuin production, it would reflect
the proteins role in animals and confirm a link with lifespan extension, at least for yeast. The
yeast lived 60-80% longer than normal due to the resveratrol, even at low doses.
Subsequent experiments on human cells have revealed that resveratrol activated a similar
pathway, requiring the human gene, SIRT1. This ensured the survival of 30% of resveratrol-
treated human cells irradiated with gamma rays, compared to 10% of untreated cells.
Tests performed on flies and worms have proved convincing and tests on mice are ongoing.
From these studies, it appears that it is not so much the antioxidant potential of resveratrol that
activates the famous longevity gene, but its chemical structure. It seems resveratrol actually
accelerates the rate of the reaction known as desacetylation and the activation of certain
genes depend on this.
We have described how it is the inability of senescent cells to perfectly replicate DNA in each
new cell that leads to aging, and ultimately death. It is at this senescence point that DNA starts
to make mistakes: fragments of DNA become active and reproduce, preventing cells from
behaving normally. Resveratrols main anti-aging benefit is that, by stimulating the longevity
gene, it reduces this DNA fragmentation by exactly 60%.
As we can see, the results are extremely promising! So much so, that the European Union has
awarded a grant to scientists researching the health benefits of resveratrol. This European pro-
ject, Marek Murias, will evaluate the antioxidant and anti-proliferation effects of resveratrol glu-
curonide and sulphate metabolites produced by the liver during resveratrol metabolism.
As we have seen, resveratrol works well with certain other nutrients which enhance its effects.
A particularly favourable synergy occurs when resveratrol is combined with substances that
modulate gene expression, improve biomarkers of aging and boost disease-fighting mecha-
nisms.
The most interesting of these substances are pterostilbene and polydatin, two resveratrol deri-
vatives, as well as nutrients such as quercertin, fisetin and pinebark extract which add to this
synergy.
Pterostilbene
Pterostilbene has been used for centuries in ayurvedic medicine. Pterostilbene and resvera-
trol are both stilbenes, directly related in terms of structure, which perform similar, though not
identical, functions. Researchers have shown that they act synergistically to activate longevity
genes. Pterostilbene also mimics many of the effects of calorie restriction.
It also has a number of anti-inflammatory, antineoplastic and antioxidant properties and regu-
lates the genes involved in the development of cancer, atherosclerosis, diabetes and the inflam-
mation that is at the root of numerous diseases.
Its various properties therefore enable it, in conjunction with resveratrol, to help counter certain
effects of aging.
Polydatin
This synergy is further enhanced by combining the resveratrol, or its derivatives, with other
nutrients:
Quercetin is a powerful antioxidant and highly effective anti-inflammatory used to prevent car-
diovascular disease, metabolic syndrome and cancer. It may improve longevity simply by redu-
cing the impact of certain chronic diseases. But it also seems to have an effect independent of
this, with data suggesting it has a direct effect on extending life expectancy, at least in simple
laboratory organisms. Portuguese researchers have shown that, by increasing resistance to oxi-
dative stress, quercetin prolongs the life span of laboratory yeast cells in culture by 60% 12.
A team of German biologists have shown that feeding C.elegans worms a flavonoid-rich diet
improved their health and total longevity 13. They identified a total of four specific genes which
seemed to be activated by quercetin 14.
Other scientists have reported findings suggesting that quercetin may mimic certain effects of
calorie restriction on life expectancy.
Fisetin
Fisetin, a flavonoid extracted from Buxus sinica, has a stabilising effect on resveratrol by preven-
ting its breakdown. Most significantly, it sends a switch-on signal to carrier cells of the anti-
aging gene by ensuring protection of DNA and neurons, particularly during periods of oxidative
stress.
Pine bark extract from the Landes maritime pine contains very powerful antioxidants polyphe-
nols called oligoproanthocyanadins or OPCs. OPCs, polymers of catechin and epicatechin, are
able to neutralize all reactive oxygen species or free radicals. They also have a potent anti-inflam-
matory effect via a number of pathways:
they block activation of NF-kB in macrophages inhibiting production of adhesion
molecules;
they inhibit, in vitro, the activation of IL-1 pro-inflammatory cytokines. Ex-vivo,
they block the activity of COX 1 and 2.
In addition, they improve endothelial function, thus lowering the risk of cardiovascular disease,
and reduce venous insufficiency. Lastly, they help lower blood sugar levels and inhibit absorp-
tion of carbohydrates. They promote reductions in systolic pressure, improvements in the lipid
profile and normalization of platelet activity.
Niacinamide, or nicotinamide, is one of two forms of vitamin B3, the other being niacin. Niaci-
namide is needed for hundreds of enzyme reactions. Research has demonstrated its beneficial
effects for a wide range of health problems, in particular, its ability to increase activity of the
anti-aging protein, SIR2p.
References
1 H . Arichi et al (1982) Effects of stilbene components of the roots of Polygonum cuspidatum on
lipid metabolism. Chem. Pharm. Bull. 30, 1766-70.
2 Losa G.A. Resveratrol modulates apoptosis and oxidation in human mononuclear cells. Eur. J. Clin.
Invest. 2003 Sept.; 33(9): 818-23.
3 Pace-Asciak C.R. The red wine phenolics trans-resveratrol and quercetin block human platelet
aggregation and eicosanoid synthesis: implications for protection against coronary heart disease.
Clin. Chim. Acta, 1995; 235: 207-19.
4 Pozo-Guisado E. et al. The antiproliferative activity of resveratrol results in apoptosis in MCF-7 but
not in MDA-MB-231 human breast cancer cells. J. Steroids Biochem. Mol. Biol. 2003; 84: 149-57.
5 Potter G.A. et al. The cancer preventive agent resveratrol is converted to the anticancer agent
piceatannol by the cytochrome P450 enzyme CYP1B1. Br. J. Cancer. 2002 Mar. 4; 86(5):774-8.
6 Y ang Y. B. et al. Effects of resveratrol on secondary damage after acute spinal cord injury in rats.
Acta. Pharmacol. Sin. 2003; 24: 703-10.
7 Culpitt S. V. et al. Inhibition by red wine extract, resveratrol, of cytokine release by alveolar macro-
phages in COPD, Thorax, 2003 Nov.; 58(11): 592-6.
8 R usso A. et al. Red wine micronutrients as protective agents in Alzheimers like induced insult.
LifeSci. 2003; 72: 2369-79.
9 Savaskan E. et al. Red wine ingredient resveratrol protects from beta-amyloid neurotoxicit. Geron-
tology 2003; 49: 380-3.
10 Chanvitayapongs S. et al. Amelioration of oxidative stress by antioxidants and resveratrol in PC12
cells. Neuroreport 1997; 8: 1499-502.
11 H owitz K. T. et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan.
Nature. 2003 Sep. 11; 425 (6954): 191-6.
12 B elinha i. et al., Quercetin increases oxidative stress resistance and longevity in Saccharomyces
cerevisiae. J. Agric. Food Chem. 2007 March 21; 55(6): 2446-51.
13 P ietsch k. et al., Quercetin-mediated lifesspan in Caenorhabditis elegans is modulated by age-1,
Sek-1, daf-2 and unc-43. Biogerontology 2008 Nov. 29.
14 S aul n. et al., Quercetin-mediated longevity in Caenorhabditis elegans: is DAF-16 involved? Mech.
Ageing Dev. 2008 Oct.; 129(10): 611-3.
Oxaloacetic acid, or its ionic form, oxaloacetate, is naturally present in freshly-picked apples and
oranges. However, it is extremely unstable and does not last more than a day at room tempera-
ture.
Oxaloacetate is present in every cell of the body and its metabolites are directly involved in
mitochondrial energy production as it is an intermediate in the citric acid or Krebs cycle and in
gluconeogenesis. Oxaloacetic acid is therefore a dicarboxylic acid essential for metabolism.
The body produces oxaloacetate but, in certain cases, genetic mutations affect production
of pyruvate carboxylase, a mitochondrial enzyme that converts pyruvate into oxaloacetate,
making the body unable to produce enough oxaloacetate.
Oxaloacetic acid is a small molecule which, when taken orally as a soluble supplement, is dis-
tributed throughout the body via the bloodstream 10. It is naturally very unstable and does not
last more than a day at room temperature. The recent development of a complex process means
that oxaloacetate can now be stabilized and made totally bioavailable. This substance has also
just received one of very first patents within the framework of lifespan extension, for its efficacy
in mimicking the effects of calorie restriction. In this sense, it is similar to resveratrol although,
as we will see, it acts via different mechanisms.
it significantly boosts antioxidant status. Oxaloacetic acids unique abilities are the
result of its capacity for transporting antioxidants into mitochondria, it being able
to cross the mitochondrial membrane easily 17;
it regulates glycaemia and improves insulin resistance;
it combats denaturation of nucleic acids in mitochondria;
at high doses, it protects mitochondrial DNA in cells of brain tissue 19. As it can cross
the blood-brain barrier, it thus protects the brain from certain damage;
it reduces toxicity from certain heavy metals in the cells of pancreatic islets and
neurons 31, 32;
it protects neurons from hydrogen peroxide 33 and free radicals 20, 21, 34, 35;
in combination with zinc, it ensures protection from DMLA for retinal pigment epi-
thelial cells;
it has a positive effect on arthritis and joint stiffness;
it blocks production of fat by the body;
it repairs DNA in skin cells and other tissue damaged by UV rays;
it improves endurance test results in mice;
it reduces certain symptoms of chronic alcoholism (weight loss, nausea, diarrhoea,
shaking), or those of a hangover following over-consumption of alcohol;
it has a positive effect on the digestive tract of rats and inhibits potential ulceration36;
it reduces apoptosis (programmed cell death);
it delays the appearance of most complications associates with age-related diseases;
Oxaloacetate is one of the most effective substances at reproducing the benefits of calorie res-
triction, so avoiding the need to actually reduce food intake. Calorie restriction - reducing food
intake by 30% to 50% - is the only recognized method of prolonging life in mammals.
It produces changes in metabolism and in the expression of genes which increase lifespan. It has
a beneficial effect on most biological parameters and delays the development of degenerative
diseases (dementia, Alzheimers, Parkinsons).In humans, it reduces the risk of atherosclerosis,
peaks in fasting blood sugar, systolic and diastolic blood pressure, triglycerides, LDL-cholesterol
and total cholesterol, and thus has a direct effect on reducing incidence of cardiac disease, kid-
ney disease, type 2 diabetes and cancer 1, 3.
The ability to mimic these effects through nutritional supplementation constitutes a major
advance in combatting the aging process and degenerative diseases. Calorie restriction is, of
course, very difficult to sustain on a daily basis. Therefore, any substance that can mimic its
effects has surely earned a place among the key advances in anti-aging nutrition.
Oxaloacete is one of the few products shown to increase the lifespan of male mice which, like
humans, do not live as long as females. Research showed that at the 50% mortality mark, oxa-
loacetate increased average lifespan by around 25% compared to controls.
In addition to these remarkable results, it was also reported that mice given oxaloacetate had
minimal inflammation and arthritis symptoms and a lower tendency to age-related curvature of
the spine. Furthermore, bone density was higher than in the control group suggesting efficacy
against osteoporosis. Further studies have shown that oxaloacetates activity is not restricted to
mice. Research on Drosophila melanogaster (the common fruit fly) has demonstrated an ave-
rage increase in lifespan of 20% following the addition of oxaloacetate to food. Similar results
were also obtained with the roundworm C. elegans.
While different species react in different ways and there is no absolute certainty over oxaloace-
tates effects in humans, it is nevertheless possible to make reasonably confident assumptions
Oxaloacetate mimics the cell conditions that result from calorie restriction by restoring the
NAD+/NADH ratio. It crosses cell membranes without difficulty and is easily reduced into malate
by the enzyme malate dehydrogenase in cytosol. This reaction also converts NADH into NAD+,
increasing the NAD+/NADH ratio. This increase is related to the signalling effect which enables
the expression of beneficial genes, so imitating the effects of calorie restriction.
We dont fully understand all the reasons why calorie restriction leads to a longer life, but certain
of them have been identified:
Therefore, supplementing with oxaloacetic acid offers one of the safest methods of mimicking
calorie restriction.
The effects of oxaloacetic acid supplements have been tested on humans and animals.
Yoshikawa 10 first studied oxaloacetic acid for its potential in treating diabetes, having identified
it as the active ingredient of Euonymus alata extract, a traditional herb still used today for trea-
ting diabetes in Asian countries after hundreds of years use 23.
Yoshikawa showed that taking sodium oxaloacetate orally allowed it to pass into the bloodstream
within an hour and lowered fasting glucose levels in the bloodstream and urine to normal levels
in the majority of patients, without any side effects.
In animal studies, Yoshikawa showed that sodium oxaloacetate increased tissue absorption of
glucose by 300% in diabetic animals and by 180% in normal animals.
The anti-diabetic properties of oxaloacetic acid should be considered inasmuch as they provide
a safer means of mimicking calorie restriction than conventional methods. The most common
treatment of diabetes uses metformin which, while effective, carries a slight risk of lactic aci-
A consensus exists that calorie restriction is very effective at reducing the incidence of cancer1.
Therefore, it is highly likely that calorie restriction mimetics may have the same effect. Could
an oxaloacetic acid supplement reduce the ability of certain types of cancer cells to reproduce,
without affecting normal tissue?
Research has clearly shown that, by introducing oxaloacetate to human lung cancer tissue in
vitro, the reproduction of cancer cells can be halted while normal cells remain unaffected
even six weeks after the oxaloacetic acid solution had been removed 26. Interestingly, the herb
alatus itself prevents the spread of certain types of cancer whilst maintaining low cytotoxicity.
Its mechanism of action seems to have inhibiting effects on matrix metalloproteinases (MMP)
which are involved in tumour metastasis 27. Of course, while these in vitro results are extremely
encouraging, they now need to be confirmed in vivo.
Supplementation with oxaloacetic acid successfully mimics some of the effects of calorie res-
triction observed in animals. Animal studies show an increase in lifespan and other significant
health benefits, including protection of mitochondrial DNA, the retina, and neuronal and pan-
creatic tissues. Human studies suggest a substantial decrease in fasting blood sugar and impro-
ved insulin resistance.
In addition, studies into chronic and acute toxicity point to very low toxicity for oxaloacetic acid,
similar to that of vitamin C.
As a calorie restriction mimetic, oxaloacetate induces a number of beneficial changes to gene
expression which considerably extend lifespan.
Following its evaluation, the American FDA has designated oxaloacetate an orphan
drug for the treatment of glioma (including glioblastoma). This designation is used to
encourage the development of natural substances which help fight orphan diseases and
which would not normally be developed due to the very small number of people affected
by these rare diseases.
In addition, oxaloacetate is currently the subject of clinical trials investigating its potential
in the treatment of Parkinsons disease. Results of these studies will be published shortly.
The by-products of oxaloacetate degradation in the body are well-documented and include
pyruvate, aspartic acid and malate. Once in the body, oxaloacetate (a water-soluble ion) can
react in a number of ways.
One such reaction is the conversion of oxaloacetate into L-malate, catalysed by the enzyme
malate hydrogenase. During this conversion, NADH is also converted into NAD+, considerably
increasing the NAD+/NADH ratio.
When calorie intake is cut, the body produces the glucose it needs from pyruvate, in a process
called neoglucogenesis. Studies on calorie-restricted animals show a change in the activity of
metabolic genes resulting in the production of enzymes responsible for neoglucogenesis 3.
Within this neoglucogenesis process, NADH is converted into NAD+ when biphosphoglyce-
rate is converted into 3-phosphoglyceraldehyde the result of which is an increase in the NAD+/
NADH ratio.
In studies on yeasts, the increase in this ratio was clearly associated with calorie restriction and
led to an increased lifespan 11, 12.
For human cells, prolonged lifespan is linked to increases in nicotinamide phosphoribosyltrans-
ferase and NAD+ precursors 14.
Energy levels and lifespan also seem to be linked with the activity of AMPK 5-adenosine mono-
phosphate-activated protein kinase, which is stimulated by the increase in the NAD+/NADH
ratio 15. AMPK activation also seems to be the underlying mechanism of metformin, an anti-
diabetic drug which has been suggested as a calorie restriction mimetic and which has been
shown to increase lifespan in mice 16. In order to achieve extended lifespan through calorie
restriction, AMPK must therefore be activated 4, as demonstrated by a control group of oxaloa-
cetate-supplemented animals which showed a significantly increased lifespan.except when
AMPK was not activated 7.
So, we can conclude that when oxaloacetate supplementation is administered, activation of
AMPK via an increase in the NAD+/NADH ratio leads to mimicking of calorie restriction.
It may be that protecting mitochondria also contributes to the extension in lifespan of animals
supplemented with oxaloacetate.
Either way, it has been demonstrated that calorie restriction delays the cumulative effects of
mitochondrial DNA mutations 6. Animals with abnormal mitochondrial function clearly aged
prematurely 22.
The conclusion appears logical: maintaining and improving mitochondria through oxaloace-
tate supplementation is likely to increase lifespan.
Animal studies have clearly identified that substances which can curb the action of insulin can
increase life expectancy - calorie restriction works at this level too. All the synthetic and natural
substances that reduce insulinaemia and glycaemia also restrict the aging process.
In allopathic medicine, the drug most often prescribed to increase insulin receptor sensitivity
and inhibit glucose production by the liver (neoglucogenesis) is metformin. Recent studies
demonstrated that metformin blocked the action of certain genes which contribute to this
neoglucogenesis and activated other genes responsible for glucose metabolism, in exactly the
same way as calorie restriction.
Chinese and ayurvedic medicine utilise a number of plants that are still relatively unknown
in Western medicine. One such plant is Berberis vulgaris, or European barberry, the berries of
which contain a powerful plant alkaloid called berberin. Traditionally used for its immune-sti-
mulant, anti-fungal, and anti-bacterial properties, and its ability to control intestinal disorders,
this substance has emerged as an excellent mimetic of metformin.
Like calorie restriction, berberine induces mild to moderate stress at a cellular level which in the
long-term is beneficial. In fact, when a cell suffers temporary stress, it produces the metabolic
enzyme AMPK (Adenosine Monophosphate Kinase) which prioritises the prevention or repair
of cell damage over synthesis of proteins, fats or carbohydrates which require a lot of energy.
Therefore, all available energy is diverted to cell damage prevention and repair at the expense of
other functions which have to take second place. This change to survival mode forces the cells
to delay their non-essential functions and re-direct resources towards protection and repair.
Such is the extent of berberines properties it can be compared with metformin. The most repre-
sentative studies focus on the efficacy of berberine versus metformin in patients with type II
diabetes 38, whether or not associated with dyslipidaemia 39.
With properties traditionally-recognised as beneficial to immunity, cardiovascular and intestinal
health, berberine also appears to be an excellent anti-aging nutritional supplement.
Research on berberine suggests the recommended daily amount to be between 1g and 1.5g
a day, spread over two or three doses, taken before the three main meals of the day. In order to
benefit fully from berberine supplementation, it should be taken for at least three months, as its
optimal activity is only apparent after two weeks regular use.
Apart from a few reported cases of mild, temporary constipation immediately after beginning
supplementation, berberine is completely free of side-effects.
Research on adult and embryonic stem cells has raised considerable hope in
the field of medicine and the fight against aging and age-related diseases.
The use of embryonic stem cells is the subject of great ethical debate world-
wide and is not authorised in all countries - it is banned in France, for example.
Human stem cells were first isolated, cultivated and differentiated from embryos in 1998. There
are several types of stem cells which differ according to their source:
totipotent cells obtained in the first four days of growth of the embryo - they are
the only ones that allow the development of a human being;
pluripotent stem cells derived from the blastocyst, destined to produce all body
tissues;
multipotent stem cells present in the adult body, which differentiate into several
types of cells;
unipotent stem cells that produce only one type of differentiated cell.
Stem cells are naturally present in organs and enable cell regeneration. In certain tissues, cells
are constantly renewed. Their stem cells generate differentiated cells in order to replenish
cells when needed. Red blood cells, the bodys oxygen carriers, live for only 120 days and are
constantly replaced by new cells formed from stem cells in bone marrow. In the digestive sys-
tem, intestinal stem cells constantly differentiate into cells that line the intestine, thereby repla-
cing those that are sloughed off. Skin stem cells make skin while stem cells in the hair follicles
make hair. Stem cells produce a wide range of immune cells that differentiate into adult immune
cells in response to specific signals from hormone-like substances, levels of which increase with
infection and inflammation.
Hence the importance of the research conducted in recent years by certain scientists who, with
the use of nutrients and plant extracts, have been able to stimulate and increase the amount of
adult stem cells in bone marrow. For regeneration activity purposes, scientists have been par-
ticularly focusing their research on bone marrow as these cells evolve daily by producing new
lines of red blood cells, white blood cells and platelets. Mature cells are then released into the
bloodstream where they exert their full regenerative and vital functions.
The nutrients that studies have revealed to be the most active include folic acid, vitamin B12,
iron and other better- or lesser-known components such as fucoidan, Polygonum multiflorum
extract, wild blueberry extract and beta 1.3/1.6 glucan.
On October 9, 2012, Dr. John B. Gurdon of Cambridge University in England and Dr. Shinya Yamanaka of
Kyoto University in Japan were awarded the Nobel Prize in Medicine for their work on induced pluripo-
tent stem cells (or IPS cells).These two scientists have helped lay the foundations for regenerative medi-
cine with their concept of regenerating all human body tissues through the injection of pluripotent cells.
This new technology thus enables the mechanisms of aging to be targeted in advance. Through these
scientific advances, any somatic cell can be restored to an all-powerful pluripotent stem cell state, from
a sliver of skin, blood cells or a hair. Rejuvenated cells obtained in this way are identical in all respects to
those created decades earlier.
What was just the hope or vision of a few people will tomorrow become a
reality
The immune systems first line of defence are NK cells natural killer cells. Research suggests
that when people in poor health increase their intake of gluconutrients, there is a sharp increase
in the number of their NK cells.
A number of polysaccharides have effects on different immune responses. One in vitro study
looked at fucoidans immune-modulatory effect. Mouse spleen lymphocytes became cyto-
toxic to tumor cells after culture with fucoidan. Macrophages treated with fucoidan exhibited
induced tumoricidal activity, increased phagocytosis, lysosomal enzyme activity and produc-
tion of nitrite, H2O2, tumour necrosis factor (TNF)-alpha and interleukin 6. The tumoricidal effect
of macrophages induced by fucoidan appeared to be mainly mediated by free radical and
cytokine production. These findings suggest that fucoidan is an activator of lymphocytes and
macrophages and that this property could contribute to its effectiveness in the immunopreven-
tion of cancer1.
Fucoidan has shown a marked anti-cancer effect in animal models, whether injected into the
bloodstream or the peritoneal cavity, or administered orally. Specifically, a significant reduction
in cancer development was observed in mice and rats in which cancer cells had been implanted.
This effect has been noted in several animal cancer models, including leukaemia and breast
As with other substances extracted from algae, certain concentrations of fucoidan have exhi-
bited the ability to stimulate bone marrow stem cells.
A clinical study in which healthy volunteers ingested 3g of fucoidan a day for 12 days demons-
trated a significant increase in the proportion of haematopoietic stem cells in peripheral blood.
No side effects were observed.
Other studies have shown that fucoidan led to an increase in alkaline phosphatase activity at
a molecular level, and improved expression of genes specific to osteogenesis and osteogenic
differentiation, thus promoting bone regeneration.
Therefore, by acting directly on the mobilisation of stem cells, fucoidan facilitates more effective
repair of damaged tissues, both in cardiovascular terms, following a heart attack, as well as in
the joints or vital organs.
As we have seen already, astragaloside IV is already known for its telomere-lengthening effects.
The adaptogen plant Astragalus membranaceus from which astragaloside IV is extracted, has
been used for hundreds of years in traditio-
nal Chinese medicine, to increase vitality and
strength, amongst others.
Research shows this saponin stimulates the
immune system in various ways, in particu-
lar, by increasing stem cells in the spinal cord
and lymphatic tissue and encouraging them
to develop into active immune cells.
Astragaloside IV also supports proliferation
of mesenchymal stem cells, pluripotent tis-
sue stem cells that help form skeletal connec-
tive tissue such as bone and cartilage.
Polygonum multiflorum
Extract of Polygonum multiflorum or FO-TI, is recognised in Chinese medicine as an effective
blood tonic, and in particular as a major factor in longevity due to its ability to increase levels of
circulating superoxide dismutase (SOD) and monoamine oxidase.
Mouse studies conducted in Taiwan show that after daily administration of high-dose (200-
1000mg/kg) Polygonum multiflorum, significant improvements were noted in red blood cells,
and in particular, a higher percentage of hematocrit compared with a control group. This
research also shows that doses at this level stimulate proliferation of stromal and haematopoie-
tic stem cells in bone marrow.
L-carnosine
L-carnosine, which acts on the maintenance of telomeres (see previous chapter) improves repli-
cative capacity of myoblast cultures. Certains myoblasts, called satellite cells, remain on the
periphery of muscle fibres, intervening in their repair when damaged. However, with increasing
age comes sarcopaenia (loss of muscle mass) and the satellite cells are no longer able to repair
the damage.
A study on myoblasts - the stem cells responsible for skeletal muscle formation - showed that
supplementing with L-carnosine increases their replicative capacity and also reduces the acti-
vity of beta-galactosidase.
Vitamin D3
Over 90% of our vitamin D3 needs should in theory be met by exposure to the sun, but popula-
tions in Western countries, such as France, Belgium, the United States, Switzerland and Canada,
actually have inadequate levels of vitamin D, especially during the winter. We are now aware of
the risks associated with a lack of vitamin D3 but scientists are providing increasing evidence
of its fundamental role in cell division and differentiation and its effects on the immune system.
In fact, inadequate vitamin D levels are linked to almost all age-related problems, including
cancer, vascular disease and chronic inflammation.
Research suggests that doses of 5000 IU a day could offer multiple health benefits. This is also
the dose recommended by the Vitamin D Council.
Studies have also shown that vitamin D, combined with other natural substances, may have
effects on adult stem cells and as a result, increase neurogenesis and improve cognitive abi-
lity. Researchers therefore tested a synergistic combination of extracts of blueberry, green tea,
L-carnosine and vitamin D3. When this unique combination of substances was given to rats,
there was a clear decrease in oxidative stress but more significantly, it was shown to promote
the proliferation and migration of neural stem cells towards damaged brain cells (following a
stroke for example).
Click here for a formulation that naturally stimulated stem cell production
For many years, German scientists have been focusing on the hydra (a freshwater polyp) which appears
to be immortal Indeed, if you cut a hydra in half, it quickly regenerates. Its ability to do so is linked to
its stem cells which do not age and can proliferate indefinitely.
Gene analysis has revealed that it is the long-recognised FoxO3 gene, associated with longevity in
centenarians, which is also found in the hydra. Whats more, when researchers inactivated this FoxO3
gene, they observed a significant decrease in the number of stem cells and less effective function of the
immune system.
These results show that the FoxO3 gene plays an important role in the aging process and offers hope in
the area of gene therapy and immortality.
References
A nna-Marei Boehm, Konstantin Khalturin, Friederike Anton-Erxleben, Georg Hemmrich, UlrichC. Klos-
termeier, Javier A. Lopez-Quintero, Hans-Heinrich Oberg, Malte Puchert, Philip Rosenstiel, Jrg Wittlieb,
Thomas C. G. Bosch., FoxO is a critical regulator of stem cell maintenance in immortal Hydra. PNAS
2012; published ahead of print November 12, 2012, doi:10.1073/pnas.1209714109.
1 C hoi E.M. et al., Immunomodulating activity of arabinogalactan and fucoidan in vitro. J. Med. Food,
2005 Winter, 8(4): 446-53.
2 The role of NK cells in antitumor activity of dietary fucoidan from Undaria pinnatifida sporophylls
(Mekabu), Planta Med. 2006 Oct. 20, Department of Pathology, School of allied health sciences,
Kitasato University, Kitasato Kanagawa, Japan.
3 P atchen M.L. et al., Glucan: mecanisms involved in its radioprotective effect, J. Leux Biol., 1987,
42:95-105.
4 Enhancement of radioprotection and anti-tumor immunity by yeast-derived beta-glucan in mice,
J. Med. Food, 2005 Summer, 8(2):154-8.
5 Cell Stem Cell, published on-line on December 24th 2009.
Saikosaponin A
Researchers are constantly and actively engaged in the quest to hold off the ravages of aging
and extend human lifespan. The latest advances in genetics are generating significant new opti-
mism 1.
Scientists have made a genetic breakthrough which they say could extend human lifespan and
even protect against cancer. Experiments on mice have shown that their lifespan could be pro-
longed by up to 45%, without developing cancerous tumours. This suggests that under certain
conditions, humans could live to almost 125 years, cancer-free, because the genes thought to
be responsible are naturally present and have identical roles - in both mice and humans.
Geneticists and cancer experts have reached the same conclusions on the identification and
role of these genes:
The telomerase gene boosts the immune system and in particular, lengthens the shortest
telomeres - the tips of chromosomes. It responds exceptionally well to astragaloside IV
and cycloastragenol.
The P16 gene, also a tumour suppressor gene, completes the picture by controlling
anarchic cell mitosis. Recently, it has been possible to use P16 gene concentration, which
increases in human tissue with age, in blood tests as a biomarker for cell aging.
Manuel Serrano, a Spanish researcher at the CNIO, told a conference: When P53 and P16 genes
were activated in mice, cancer incidence was reduced to practically zero. The Spanish scientists
concluded that the activation of three genes telomerase, P53 and the tumour-suppressor P16
represented a major contribution to the prevention and regression of tumours by apoptosis
(programmed cell death). They added: We do not think that the mice lived longer because they
didnt have cancer, but because these genes protected them against aging.
This is therefore the first time that scientists have been able to prolong lifespan in mice in this
way (by inserting an extra copy of the three genes), while protecting them from cancer. Until
now, the mice were aging without cancer, but their lifespan did not increase significantly. And
only calorie restriction enabled their life expectancy to be extended. These transgenic mice,
able to self-reproduce, have strengthened their new DNA model, thus creating a group of
supermice, with longer lifespans of 4.5 years compared with the average 3 year lifespan, and
that benefit from optimal protection against cancer.
Bupleurum falcatum or buplevre, belongs to the Apiacaeae plant family and is used in traditional
Chinese and Japanese medicine. It is widely considered to be a cell detoxifier that helps fight
chronic infection and inflammatory conditions (particularly hepatitis). Bupleurum has recently
increased in popularity due to favourable results achieved in cancer treatment. Its active prin-
ciples are the saikosaponins A, B, C and D. Of these, it is the A form, a triterpenoid glycoside, that
activates the tumour-suppressing P16 gene, but it is extremely rare and expensive - you would
need to consume 50g of Bupleurum to obtain 4mg saikosaponin A. This new plant substance -
saikosaponin A has been specifically selected and isolated in order to activate the P16 tumour
suppressor gene 2.
The benefits of saikosoaponin A are enhanced when it is combined, though not simultaneously,
with other anti-aging substances. Supplementation with saikosaponin A is recommended on a
non-continuous or alternating basis, ie, every other week, with astragaloside IV or cycloastrage-
nol, which activate the telomerase gene, and with resveratrol and its derivatives, which activate
the P53 gene.
Though it is still too soon to establish a strict administration protocol for this product, the fol-
lowing can be used as a basis:
Either a 4mg dose of saikosaponin A in the evening, and astragaloside IV and/or
cycloastragenol in the morning.
Or you can alternate these products every other day.
No adverse reaction has been observed to date.
Caution: as saikosaponin A is a vasodilator, comparable to niacin, it should not be taken by anyone using
coronary vasodilators, or by pregnant women or nursing mothers.
References
1 M aria A. Blasco, Bruno M., Bernardes de Jesus: CNIO scientists successfully test the first gene therapy
against ageingassociated decline. Fundacin Centro Nacional de Investigaciones oncolgicas
Carlos III.
2 Wu W. S., Hsu H. Y.: Involvement of p-15(INK4b) and p-16(INK4a)geneexpression in saikosapo-
ninA and TPA-induced growth inhibition of HepG2 cells. Biochem Biophys. Res. Commun. 2001 Jul.;
13;285(2):183-7.
3 Sun Y., Cai T. T., Zhou X. B., Xu Q.: SaikosaponinA inhibits the proliferation and activation of T cells
through cell cycle arrest and induction of apoptosis. Int. Immunopharmacol. 2009 Jul.; 9(7-8):978-
83. doi: 10.1016/j.intimp. 2009.04.006. Epub 2009 Apr 16.
4 Yano H., Mizoguchi A., Fukuda K., Haramaki M., Ogasawara S., Momosaki S., Kojiro M. The herbal medi-
cine sho-saiko-to inhibits proliferation of cancer cell lines by inducing apoptosis and arrest at the
G0/G1 phase. Cancer Res.1994 Jan. 15;54(2): 448-54.
These two substances are, amongst others, powerful antioxidants that can protect the brain
from free radical damage. Centrophenoxines therapeutic benefits have been particularly noted
in cases of cerebral atrophy, age-related brain damage, cerebral congestion, chronic alcoholism
or drug abuse.
Clinical studies on geriatric patients showing symptoms of confusion, extreme weakness, dis-
turbances in memory or intellectual concentration, have revealed marked progress and impro-
vements in symptoms after just a few weeks treatment with centrophenoxine. Regular use can
thus prevent mental deterioration and improve memory performance in both healthy indivi-
duals and those suffering from dementia 3.
In a double-blind study of 50 elderly subjects suffering from moderate dementia, centrophe-
noxine stimulated memory significantly more than a placebo. It also produced general impro-
vements in patients condition 9.
Centrophenoxine stimulates brain function. It increases neuronal uptake of glucose and oxygen
as well as production of carbon dioxide, indicating increased brain energy (ATP) production.
Research on rats showed a steady increase in cerebral metabolic activity, even under hypoxic
conditions, and an increase in cortical electrical activity (a reflection of brain metabolic activity)
in almost 40% of adult or elderly animals.
Superior cholinergic
DMAE, the main constituent of centrophenoxine, is converted into choline by the liver by adding
a methyl group. Centrophenoxine thus supplies DMAE and choline to the brain. Choline, a simi-
lar substance to B group vitamins, comes from the diet (from liver, meat and eggs) and is pro-
duced in small amounts by the body. However, too little choline can be provided by the diet, as
a result of food processing and of following certain diets (vegetarian or vegan) and a low intake
of choline is not good for our health 4, 5.
Indeed, choline is essential for optimal brain function and is used to produce other substances
such as acetylcholine, a neurotransmitter crucial for memory, learning and mental concentration.
It also produces two essential components of the cell membrane phosphatidylcholine and
sphingomyelin. Choline insufficiency can sometimes lead to permanent auto-cannibalization,
membrane disruption, and cell death. Furthermore, a number of studies have associated exces-
sive neuronal choline auto-cannibalization over a lifetime with the development of Alzheimers
disease.
Therefore, centrophenoxine is probably the most effective way of increasing blood and brain
levels of choline and acetylcholine.
As we age, neuronal membranes normally become less fluid and more rigid due to hydroxyl
radical damage and cross-linked proteins. This decrease in fluidity impairs the ability of neu-
ronal membranes to conduct electrical impulses. Fluidity decreases as hydroxyl-induced lipid
peroxidation increases 6.
Maintaining a good level of phosphatidyl DMAE in neuronal cell membranes through regular
supplementation with centrophenoxine thus represents an effective strategy for:
In general, production of total RNA, messenger RNA and proteins falls considerably with age.
Studies conducted on elderly rats showed that centrophenoxine significantly increased RNA
synthesis, producing almost the same levels as adult rats. RNA (derived from DNA in the cell
nucleus) allows cells to receive instructions from nuclear genes and make new proteins to
replace worn-out or hydroxyl radical-damaged proteins2.
According to data from animal studies, centrophenoxine is very effective at reducing levels of
lipofuscin 1. Lipofuscin is a residue consisting of fragments of membranes, damaged proteins
and fatty acids. It accumulates in cells in later life to the point where it sometimes accounts for
30% of their volume as shown in elderly animals. As cells store more lipofuscin, their function
becomes less effective and they can quickly die once a critical volume is reached. Lipofuscin
is sometimes called the aging pigment. It manifests as brown marks on the skin, called liver
spots or aging spots, usually on the hands and face.
Centrophenoxine is therefore one of the few substances shown to increase longevity in labora-
tory animals. Its effects in reducing levels of lipofuscin, an intracellular metabolic waste product,
are unique and directly address one of the seven deadly things identified by Aubrey de Grey.
To recap, centrophenoxine
Apple polyphenols
Plant polyphenols offer tremendous promise for solving the problems associated with aging.
In three recent studies, apple polyphenols were shown to extend lifespan in laboratory animal
models (by up to 12%).
These findings seem to be explained by the activation of genes which stimulate endogenous
antioxidant defences and by the inhibition of other genes involved in premature death.
Epidemiological studies confirm a correlation between consumption of flavonoids in general,
and apple flavonoids in particular, and human longevity.
Epimedium
Epimedium and its active substances are widely used to increase libido and promote good
sexual health. Researchers have recently been studying the effects of this plants flavonoids, par-
ticularly icariine and icariside II, its bioactive form in vivo, on the life expectancy of the C.elegans
worm. They found that icariside II increased lifespan by more than 20% by affecting intracellular
signalling molecules activated by insulin and IGF-1.
The researchers concluded that Given the extensive protective effects and safe long term use of
icariin and icariside II in humans, they may serve as promising anti-aging candidates in the future.
References
C
ai W. J., Huang J. H., Zhang S. Q., Wu B., Kapahi P., Zhang X. M., Shen Z. Y. Icariin and its derivative ica-
riside II extend healthspan via insulin/IGF-1 pathway in C. elegans. PLoS One.2011; 6(12): e28835.
doi: 10.1371/journal.pone.0028835. Epub 2011 Dec. 21.
References
arse K., Jabin S., Ristow M., L-Theanine extends lifespan of adult Caenorhabditis elegans. Eur. J.
Z
Nutr.2012 Sep; 51(6):765-8. doi: 10.1007/s00394-012-0341-5. Epub 2012 Mar. 16.
Reishi
Reishi has been in medicinal use for over 2000 years; in ancient times it was known as the mus-
hroom of immortality with good reason. Recent decades have seen a focus on the analysis of
its various constituents. Research has confirmed that reishis many properties confer all-round
protection against the various diseases which challenge our longevity.
Among the hundreds of active components in reishi, researchers have identified three specific
substances that have powerful anti-aging effects:
What makes this mushroom unique is its ability to act in many places at the same time, trigge-
ring important changes which contribute to increased longevity:
It protects cell DNA from the oxidative damage that contributes to aging and can-
cer 4;
It protects mitochondrial DNA and the mitochondria themselves from oxidative
damage that impairs their energy-producing ability and makes them ineffective,
another major cause of aging 5, 7;
It increases levels and activity of numerous intracellular antioxidant molecules,
thus reducing oxidation of cell membranes 8, 9;
It protects the kidneys from oxidative damage and therefore lowers the risk of kid-
ney failure 10;
It increases expression of a longevity gene, and extends life expectancy in several
species, from yeasts and primitive worms to mammals such as mice11,12,13, 14.
Researchers who have studied reishis effects in laboratory mice have clearly identified that it is
associated with an increase in animal lifespan of between 9% and 20%, which equates to 7-16
extra years in humans 13.
Its wide-spectrum properties prevent and treat many age-related diseases and therefore target
aging at its roots.
Animal research shows that selegiline constitutes an effective anti-aging treatment. In a study
published in a European medical journal in 1989, 132 same-age male rats were divided into
two groups. Beginning when the rats were aged 104 weeks, one group received an injection of
saline solution three times a week, and the other an injection containing selegiline three times
a week.
The rats that did not receive selegiline died at an average age of 147 weeks. After 164 weeks,
all non-treated rats had died, while all the treated rats remained alive and well. It was another
seven weeks before the first treated rat died and the last died at 226 weeks. The average lifespan
of selegiline-treated rats was 192 weeks an outcome considered remarkable by the resear-
chers since maximum lifespan for this type of laboratory rat is 182 weeks.
This increase in lifespan is due to selegilines inhibitory effects on monoamine oxydase, ena-
bling levels of dopamine to be maintained at over 30%. According to researchers, similar results
in extending lifespan could be achieved in humans. If the animal experiments translate directly
into a slowing down of the aging process, this would manifest in humans as a 24% increase in
maximum lifespan, with 25-30 more healthy years.
For the researchers, the health of the population could be maintained with 10-15mg deprenyl a
weekl starting at the age of 45 to combat aging of dopaminergic neurons. Prophylactic use of depre-
nyl seems to offer a reasonable prospect of improving the quality of life in the later decades, delaying
the time of natural death and decreasing susceptibility to age-related neurological diseases.
References
K
noll J. Deprenyl Medication: A Strategy to Modulate the Age-Related Decline of the Striatal
Dopaminergic System. Journal of the American Geriatric Society. V.40., No.8, August, 1992, pp. 839-
847.
We are also aware of other highly promising substances, currently being studied in culture or in
animals, which will undoubtedly extend the range of available resources that can significantly
prolong lifespan.
Glaucarubinone
Glaucarubinone comes from Simaruba glauca, a small South American tree. Tests conducted on
C. elegans suggest this substance extends life expectancy in these worms by 2.7 days (nema-
todes only live for a few weeks), by acting directly on mitochondrial metabolism. These findings
are therefore very promising and the researchers believe it would be beneficial to evaluate this
substance in mammals and humans in the interests of preventing age-related diseases1.
Alpha-carotene
Like beta-carotene, this carotenoid is naturally present in carrots. A large-scale US study invol-
ving almost 50,000 participants showed that it halved the risk of mortality in individuals with
a high body mass index (30 or above). The benefits were particularly noted in terms of the risk
of death from cardiovascular disease, although the risk of all-cause mortality was also lower2.
References
1 B ossecker A., Mller-Kuhrt L., Siems K., Hernandez M. A., Berendsohn W. G., Birringer M., Ristow M.
The phytochemical glaucarubinone promotes mitochondrial metabolism, reduces body fat, and
extends lifespan of Caenorhabditis elegans. Horm. Metab. Res. 2011 Apr.; 43(4): 241-3. doi: 10.1055/
s-0030-1270524. Epub 2011 Jan. 24.
2 Li C., Ford E. S., Zhao G., Balluz L. S., Giles W. H., Liu S. Serum alpha-carotene concentrations and risk
of death among US Adults: the Third National Health and Nutrition Examination Survey Follow-up
Study. Arch. Intern. Med., 2011 Mar. 28; 171(6): 507-15. doi: 10.1001/archinternmed.2010.440. Epub
2010 Nov. 22.
3 Pepper E. D., Farrell M. J., Nord G., Finkel S. E. Antiglycation effects of carnosine and other compounds
on the long-term survival of Escherichia coli. Appl. Environ. Microbiol., 2010 Dec.; 76(24):7925-30.
doi: 10.1128/AEM.01369-10. Epub 2010 Oct. 15.
4 Stvolinsky S., Antipin M., Meguro K., Sato T., Abe H., Boldyrev A. Effect of carnosine and its Trolox-
modified derivatives onlifespan of Drosophila melanogaster. Research Center of Neurology, Rus-
sian Academy of Medical Sciences, Moscow, Russia. Rejuvenation Res., 2010 Aug.; 13(4): 453-7. doi:
10.1089/rej.2009.1010.
Across the centuries, there have always been men and women who have significantly impacted
on the development of human existence, people like Pasteur or Einstein who, through their
discoveries and theories, have upset the established order of things.
Today, that mantle has been taken up by a vanguard of scientists such as Aubrey de Grey, who
leads the SENS project (Strategies for Engineered Negligible Senescence), the aim of which is
to achieve radically-extended human life expectancy by combatting the seven main causes of
aging (nuclear and mitochondrial mutations, intra and extra cellular waste, loss of cells, cellular
senescence and excessive cross-links).
Another ongoing project, supported by the Dalai Lama and the futurist Ray Kurzweil, is Dmitry
Itskovs Avatar 2045, which aims to upload a human brain into an avatar, or humanoid robot.
Itskovs intention is to free people from disease, old age and death.
Far from being science fiction, these two projects are well funded and bring together extre-
mely competent teams. They are at last pointing to the possibility of significant extensions in
lifespan and of viewing aging as a disease that can be prevented and cured rather than an ine-
vitable process. They are thus allowing us to enter a new era, that of regenerative medicine
The battle to combat the ravages of aging and extend human lifespan is intensifying. The latest
advances in genetics have raised great hopes among scientists who have been doing research
in this area for years. Moreover, if knowledge in this field continues to grow exponentially while
constraints grow linearly, there is a good chance that human immortality will be possible within
fifteen to twenty years. The important thing is to stay in good shape until then
High-quality, scientifically-supported supplements can help you do this on a daily basis and you
now have at your disposal a whole arsenal of anti-aging nutraceuticals that affect every aspect
of the aging process: the production of new mitochondria which ensures the longevity of all the
Abundance, Peter Diamandis et Steven Kotler. (Free Press - Simon & Schuster)
The future is better than you think.
On mitochondria
Improving mitochondrial function (Bruno Lacroix)
You will find all the nutritional supplements mentioned in this book
Engineering: the exacting, science-based activity of designing and producing works in accor-
dance with rigorous scientific rules. The principles on which engineering and its methodo-
logy are founded are highly logical.
Linus Freeman has been Managing Editor, since its creation in 1997,
of the newsletter NutraNews,
published by the Fondation pour le libre choix: nutranews.org