Aubrey de Grey on Longevity and Nutrition

I’m pretty passionate about nutrition and healthy living so when I stumbled across this little article called Longevity, Methuselarity, Telomere Lengths which presents some of the ideas and research of famed gerontologist, Aubrey de Grey (of whom I am also a big fan), I got sucked right in.  The Methuselarity is now!

Longevity, Methuselarity, Telomere Lengths

 

 

What does the 5,000 year old Bristle Cone Pine (Methuselah Tree) and the purported 252 year old Chinese Taoist Li Ch’ing Yuen share in common?

Answer, longevity.

Both the Bristlecone Pine and Li Ch’ing Yuen were aligned to nature’s standards, avoiding common age promoting diseases.

It’s known that clonal species such as the Methuselah Tree, have an innate capacity to avoid common disease promoting pathogens, and that’s also true for Human Beings.  Bristle Cone Pines have a dense resinous bark, which protects the species from invasion by both insects and fungi.

Similarly, Li Ch’ing Yuen’s immune system warded off generations of opportunistic pathogens and errant cancer cells, avoiding the age-related condition called in medicalese “immunosenescence.”

It’s alleged that Li Ch’ing consumed a soup of Lycium chinensis berries, better known as Gogi berries, after encountering an old sage who was twice his age and able to outperform Li in feats of endurance.

The sage shared his secret of longevity and endurance with Li.  Certain herbs like Gogi, Ginseng and Astragalus, increase longevity, and maybe helped Li Ch’ing Yuen slow his cell division clocks, by upregulating his telomerase enzymes within most of his somatic cell lines.[1][2]

Another factor that may have played a role in Li Ch’ing Yuen’s longevity, besides caloric restriction and healthy diet rich in antioxidants, was practicing Taoist philosophy, which mitigates emotional stress, by teaching adherents to cultivate balance and align their biological and emotional rhythms with nature.  Our cells act as sponges, absorbing everything from the environment, including stress, which contributes to aging, by shortening our telomere beads.

This is why I recommend consuming raw, organic, whole foods, such as Gogi berries which are a rich source of vitamins, minerals, antioxidants, sesquiterpenoids and long chain polysaccharides that deliver critical energy packets for optimal cellular processes.

Every known organism that exists well beyond an average lifespan is worth studying its environs, habits and adaptive capabilities.  Interesting studies have shown that intense exercise and caloric restriction increase mitochondrial biogenesis in both fat and muscle cells.  Mitochondrial dysfunction is linked to premature aging, because there’s less energy available to fix cellular damage such as misfolded proteins and antioxidant/oxidant imbalances.[3]

Aubrey de Grey

Aubrey_2Bde_2BGrey

Aubrey David Nicholas Jasper de Grey, the famed Bio Medical Gerontologist who coined the term Methuselarity, to describe the near future when humans will defy aging by reversing telomere shrinkage using advanced medical technologies and genetic modification, is enthusiastic about advances in our understanding of what causes biological deterioration leading to death and how we can clean up the cellular messes contributing to our finitude.[4] Some of these “therapies” as outlined in numerous articles and publications by Aubrey de Grey and his non-profit organization SENS, which stands for strategies for engineered negligible senescence.

Aubrey de Grey zeroed in on 7 age-related damages that occur in an individual’s lifetime, contributing to degenerative diseases and death.

Below are the 7 age-related dis-eases contributing to our finitude, along with the 7 strategies for mitigating and preventing them.[5]

Aubrey de Grey often uses the analogy of housekeeping, to describe the future therapeutics of gerontology.

If the roof is leaking…. fix it.  If the floors are creaking and buckling…. replace them.  Strengthen the foundations of the home as it still stands and continue the repair processes as needed.  This is what Aubrey de Grey calls “exporting entropy.”

7 Causes of ageing:

  • Cell atrophy as caused by catabolism.
  • Senescent (ageing) toxic cells caused by free radicals and metabolic byproducts such as lipofuscin.
  • DNA mutations leading to metastatic cancers.
  • Damage and genetic mutations to the 13 genes of the mitochondria. Mitochondrial dysfunction is linked to numerous degenerative conditions, especially premature aging.  The outer membrane of mitochondria has many protein based pores which allow large molecules to pass through for energy production.  Toxins can accompany ions and even pass through the inner membrane matrix to the mitochondria’s nucleus and cause gene mutations.
  • Intracellular non-functioning protein aggregates. Junk inside the cell.
  • Extracellular misshapen aggregates. Junk outside the cell.
  • Extracellular crosslinks such as advanced glycation end products (AGES). Sugar/Protein aggregates.

The 7 therapeutic strategies for promoting negligible senescence.

  • Stem cell therapy can replace any of our 200 cell types. Growth factors for the anabolic process of repairing and upbuilding atrophied organs.  Exercise which is considered a hormetic event that stimulates the anabolic repair processes.  Hormesis is a dose-response relationship in which something as a vaccine or high-intensity exercise produces negative biological effects at high doses but beneficial effects in low doses.  “What doesn’t kill you makes you stronger.”
  • Removal of unwanted cells either by invasive techniques such as laser surgery or gene silencing.
  • Utilizing a strategy known as WILT (Whole-Body Interdiction of Lengthening of Telomeres) which means deleting or silencing genes needed for telomere elongation. Now this might seem counterintuitive but Aubrey de Grey thinks that if these genes are silenced and fresh cells are seeded with already lengthened telomeres then cancer will never occur.  The new cells will have their telomeres lengthened outside the body by synthetic telomerase before they are “seeded” within someone.
  • Adding extra copies of the 13 mitochondrial genes with modifications to prevent copy sequence errors. The mitochondrial DNA is much more susceptible to oxidative damage then the heavily walled in nuclear DNA.
  • The breakdown of intracellular aggregates too big for phagocytosis using microbial enzymes. This can be crucial for improving neuronal health by reducing protein aggregates too big for autophagosomes to degrade and deliver to the lysosome.  The breakdown of junk inside the cell is known as autophagy.
  • For extracellular aggregates, Aubrey de Grey suggests immune-mediated phagocytosis by use of vaccines.
  • The breakdown of AGES (advanced glycation end products) which is when sugars crosslink with proteins non-enzymatically. An example of AGES is the browning of meat when it’s cooked.  AGES form when sugars are floating around the blood in excess and negatively interact with cellular proteins.  AGES can damage the clear crystalline proteins of the lens and cornea of the eye contributing to cataracts and blindness.  AGES can damage the delicate endothelial cells of the cardiovascular system leading to cardiovascular disease.  AGES affect ever cell of the body.

The major philosophical question that comes to my mind is can immortality be opened by a technological skeleton key?

Nutrition is the Key

I believe whole food nutrition and nutraceutical supplementation is the answer to achieving longevity and attaining “ageless vitality” throughout anyone’s lifetime.  If you’re 90 years young, or 45 years old, eating a raw organic whole foods diet, composed of fruits, vegetables, herbs and fresh water will reinvigorate you back to physical and mental juvenilia.

There’s much controversy over the question of reversing cellular senescence.   Microbiologist Leonard Hayflick showed in 1961, that human fetal cells divide 60 times before expiring in a biological process known as apoptosis or programmed cell death.  When a cell divides, a protective bead of DNA called a telomere falls off.

Telomere[1]

 

Telomeres are static beads of recurring nucleotides that protect genetic sequences on the chromosomes from degradation.  This biological phenomenon corresponds to the three cell phases Hayflick outlined in his research.  First there’s an initial primary culture, followed by an expansive period of growth and uninterrupted division which then inevitably leads to the third and last stage known as senescence or the Hayflick limit.

The word senescence comes from the Latin root senex meaning old.  Cells in senescence are no longer able to divide and carry out cellular processes.  This is because the enzyme telomerase no longer nourishes telomere strands with fresh nucleotides and cell death quickly ensues.

Hayflick performed an experiment in which he mixed aged male fibroblast cells which divided about 40 times before the experiment, into a substrate with young female fibroblast cells that had divided only 4 times prior to the experiment.

Hayflick discovered that the male fibroblast cells stopped dividing at a certain point, even when surrounded by the young female fibroblast cells.  It was as if they had a memory of their past 40 divisions and ceased dividing.

Hayflick concluded that there must be some kind of physical limit to cellular division, and science later empirically discovered telomere caps at the ends of the chromosome which shortened with each cellular division.

Interestingly, telomere shortening doesn’t occur in cancer cells, because of an enzyme known as “telomerase” which nourishes and relengthens the ends of DNA by adding strands of nucleotides from an inexhaustible reservoir within the cell.  This is the reason for Aubrey de Grey’s WILT strategy, which silences the genes in each cell that encode the telomerase enzyme.

Nutrigenomics

HE_fruits-vegetables-heart-shape_s4x3_lead

Nutrigenomics is another area of study that is showing promise, by empirically verifying old world wisdom that foods shape our physical and emotional wellbeing.  In vitro (glass tube) studies have shown that the Traditional Chinese herb Astragalus membransceus and its two secondary metabolites cycloastragenol and astragaloside IV, activate the telomerase enzyme within healthy lymphocyte and skin cells to repair shrinking telomeres.  In 2005 there was a very small 24-week double-blind, placebo controlled study, involving 36 men, aged 60 and 85 years old which was sponsored by TA sciences.

The results of the study showed slight improvement in visual acuity, immune function, skin integrity and libido.  Studies performed by companies on their own products, subject the results to considerable skepticism and criticism, and ought to be further investigated by independent researchers in a randomized controlled study to prove effectiveness while removing bias.  If the product works in a small prospective study, than it should in most instances be reproducible in a larger independent verification trial.

It’s important to point out that Japanese centenarians have lower blood levels of C-reactive protein, thrombin, interleukin 1 and 6, each of which are involved in the inflammatory cascade that underlies and drives degenerative diseases.  Interestingly, these same Japanese centenarians had increased expression of the protein adiponectin, which is involved in regulating blood glucose levels and fatty acid breakdown.  You could say genes are responsible for their longevity, but research continues to support the notion that a healthful diet, increased activity and a positive outlook, play more of a role in life-extension, than just a good familial blue print.[6]

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There has been a lot of buzz surrounding the “French paradox” which is enjoying life ad libitum (at one’s pleasure) and avoiding the common risk factors associated with such a lifestyle.  The answer to the French Paradox is most likely as complex as a post-modernist dissertation from the famed Ecole Superieure in Paris, but I would say the purported one million café’s that dot the beautiful landscape play a central role in France’s longevity paradox.  Eating fresh food rich in antioxidants such as resveratrol, communicating with friends and loved ones and maintaining a stoical threshold for stress, are all keys to a long happy life.

My Favorite Longevity Herbs

Rasayana which means rejuvenation, is an ancient Ayurvedic discipline focused on using herbs like Bacopa Monnieri and Turmeric for increasing longevity and vitality.  Ayurveda (Ayuh-Life, Veda-Science) is the oldest form of medicine, preceding Traditional Chinese and Greek healing systems by over a thousand years.[7]  What we do know about aging is that proper diet, exercise and positive outlooks greatly reduce several risk factors for age related degenerative diseases.  Ayurvedic medicine has found several powerful anti-ageing herbs which are now being used worldwide for their health promoting and anti-stress properties.

Bacopa Monnieri (Brahmi)

Bacopa_monnieri_W_IMG_1612

According to the Hungarian endocrinologist Han’s Selye, stress is a non-specific response by the body to any demand.  Whether you’re in traffic hearing several jackhammers break up a once three lane road or running from a bear in a National Park, the physiological and psychological reaction produced by the body is stress.  If certain stressors persist for any period of time exceeding your physical and psychological thresholds, it’s considered distress.  How we subjectively experience stress, depends upon multiple factors, such as personality, age, economic and social status.  Stress is ubiquitous, and the reason herbs known as adaptogens are the most popular tonics in traditional healing systems.

Bacopa Monnieri or Brahmi is a potent nerve tonic that is known to rejuvenate cognition and memory.[8]  The founder of stress research Hans Selye, systematized stress research, by outlining the three stages of stress, beginning with the alarm stage, which is followed by the stage of resistance and finally the stage of exhaustion.  In our modern, fast-paced, technological environments, individuals experience the three stages of stress with alarming consistency.

Stressful situations activate the hypothalamic-pituitary-adrenal axis (HPA stress axis) triggering the release of stress hormones such as cortisol.  This is considered the “fight-or-flight mode” which describes a heightened-stress response by the body, where blood sugar levels rise, for fueling energy intensive systems in response to a “perceived” threat.  Some of this fuel is released from the liver or the result of skeletal muscle breakdown.

This is why cortisol is considered a “catabolic” hormone, because it breaks-down and releases energy as opposed to anabolic hormones which build-up and repair cells.  If cortisol is continually elevated there can be increased fat storage in and around organs known as visceral adipose tissue.[9]  Visceral fat releases proinflammatory hormones that increase chronic inflammation and create the conditions for developing degenerative diseases and rapid ageing.

Combating excess cortisol release can be done, by consuming a healthy plant based diet and using adaptogenic herbs such as Bacopa.

Bacopa can raise your physiological and psychological “stress thresholds,” preventing mental and physical exhaustion.  Ancient Ayurvedic practitioners named Bacopa “Brahmi,” after the Hindu mythical creator “Brama the creator.”  This is because Bacopa supports the seat of consciousness and creation.

Cognitive decline is seen often in the elderly and is considered to be a “normal” part of ageing, but more and more individuals in there 8th and 9thdecades are supplementing with Bacopa and noticing an increase in mental acuity, focus and overall feelings of wellbeing.  Bacopa’s major bioactive chemical constituents are the Bacosides A and B.

These phytochemicals are potent antioxidants which can increase the intracellular antioxidant Glutathione Peroxidase, Superoxide Dismutase (SOD) and Catalase, preventing the age related oxidative induced damage seen in aged neurons.

When taken regularly, Bacopa enhances cognitive function, by increasing neuronal cell communication within the cholinergic system.  Loss of acetylcholine which is the predominant neurotransmitter in the hippocampus, is a hallmark of degenerative brain diseases such as Alzheimer’s.  Bacopa has shown an ability to reverse acetylcholine loss and lower brain inflammation.

Ashwagandha (Withania Somnifera)

ashwagandha

 

Is a powerful Ayurvedic herb and considered India’s equivalent to Korean Ginseng, because of its adaptogenic, immunomodulatory, antioxidant and anti-stress benefits.  Also known as Winter Cherry, Ashwagandha is used extensively on its own and with other herb tonics for rejuvenating senescent cells, raising stress thresholds and increasing mental acuity.

Researchers have found that Ashwagandha detoxifies cells, especially in energy intensive systems, by activating antioxidant enzymes such as Catalase and Superoxide Dismutase.[10]  Both of these antioxidant enzymes protect cells from free radicals and reactive oxygen species.  Unregulated reactive oxygen species cause immune imbalances and chronic low level inflammation.[11]

Supplementing with Ashwaganda, which contains the bioactive polyphenols known as glycowithanolides, boosts antioxidant enzymes in energy intensive systems such as the brain, liver and kidney.

Increasing antioxidant enzyme systems in the body, is the number 1 anti-ageing method for promoting radiant health.  Ashwaganda has shown an ability to mimic the body’s own anti-stress hormones which effectively lowers cortisol levels.  Cortisol is a stress hormone released by the adrenal glands which temporarily provides alertness, increased reaction time and memory function.

Overtime, excess cortisol has the opposite effects, causing insulin resistance, memory loss and depression.  The glycowithanolides in Ashwaganda work with the body to combat the negative effects of physical and emotional stress, by restoring our ability to adapt successfully to the demands of everyday life.

Turmeric (Curcuma longa)

turmeric 

By far the most popular herb in the world, Turmeric is an amazing Rasayana (rejuvenative) tonic that protects all 34 trillion cells from oxidative damage.

Free radicals such as the hydroxyl radical are oxygen atoms with unpaired electrons that cause damage to our cells.  Free radicals enter the body from the environment and are produced as a byproduct of energy production within each cell-especially energy intensive organs such as the brain, eyes, liver and kidney.

Turmeric, also known as Curcumin because of the active secondary metabolites called curcuminoids, is a spice in the Zingiberaceae family which includes the amazing pungent, tonic herb Ginger.

Traditionally, Turmeric has been used to treat numerous ailments such as inflammation, cancer, fatigue and pathogenic invasion.[12]

Recently, Turmeric has been under investigation for ability to work through the inflammatory pathways to quench inflammation and protect cell membranes from oxidative damage.  Turmeric has powerful chelating abilities, assisting the body in removing heavy metals which damage cellular proteins and enzymes.  Researchers have also discovered Turmeric’s mechanism of action in quenching inflammation, is by inhibiting the enzymes cyclooxygenase 2 and 5-lipoxygenase.

Both enzymes convert the omega 6 fatty acid arachidonic acid into proinflammatory prostaglandins, accelerating the ageing process into overdrive.

Turmeric is a powerful Rasayana tonic that can begin offering protection, by inhibiting the production of proinflammatory cytokines, reducing pain and increasing mobility.

The byproducts of fossil fuels leach into the environment and bioaccumalate in our bodies, causing damage to our cellular components, especially our mitochondrial and cellular DNA.  Turmeric is a chemopreventative medicinal, meaning it inhibits the destructive effect of persistent organic chemical pollutants that can form adducts (Latin-Drawn-toward) with our DNA, contributing to genomic instability and cancer.[13]  Our DNA is fundamental to our existence and recent research has revealed that our genome is the principle site of memory storage.[14]  Turmeric can protect both mitochondrial and cellular DNA from oxidative damage.

[1] The Lancet: Increased Telomerase activity and comprehensive lifestyle changes: a pilot study, Dean Ornish, Jue Lin, Jennifer Daubenmier, Gerdi Weidner, Elissa Epel, Colleen Kemp, Mark Jesus M Magbanua, Ruth Marlin, Loren Yglecias Peter R Carroll, Elizabeth H Blackburn; November, 2008.  Ornish et al postulated a comprehensive lifestyle change to increase telomerase activity.  Telomeres are static beads of protein complexes at the ends of chromosomes that promote DNA stability.  Researchers have discovered that individuals with poor lifestyle habits such as smoking, inactivity and overconsumption of processed meat and dairy products increase their risk of developing cancer, diabetes and obesity.  Poor lifestyle habits are also correlated with low telomerase activity which effects telomere length leading to genomic instability and increased risk for age-related diseases.  Telomerase is the enzyme which has the potential to re-lengthen telomeres.  Ornish et al postulated that if poor lifestyle habits negatively impact telomere length then healthy lifestyle changes must produce the opposite effect.  Employing a comprehensive lifestyle modification program that included a whole foods diet high in fruits, vegetables unrefined grains and legumes with moderate aerobic exercise and in group support for duration of 3 months-resulted in a 29%-84% increase in telomerase activity.  Telomerase activity was measured in PBMCs (peripheral blood mononuclear cells) which are immune cells.  The significance of increased telomerase activity within white blood cells means healthy lifestyle changes lower inflammation, diabetes and cardiovascular health which are the top three causes of disease and death in the world.

[2] APS Acta Pharmacologica Sinica: Autophagy in ageing-associated diseases, Li-qiang He, Jia-hong Lu and Zhen-yu Yue, February 18th 2013.  Caloric restriction is a key to longevity in many species such as C elegans, mice and humans because it activates autophagy which is the removal of junk inside the cell.  Autophagy (Greek meaning auto-self, phage-eat) is the cells waste removal process that functions best when fewer calories are consumed.  Researchers discovered that autophagy can be upregulated, especially during times of caloric restriction.  The MTOR protein which is involved in anabolism by increasing protein synthesis and alerting cells such as skeletal muscle there’s anabolic building material outside the cell to bring in for repair and growth.  MTOR or mammalian target of rapamycin inversely regulates autophagy, suppresing autophagocytosis when nutrients and growth factors such as IGF1 are present.

[3] PLoS Genetics: Editorial, Entropy Explains Aging, Genetic Determinism Explains Longevity, and Undefined Terminology Explains Misunderstanding Both, Leonard Hayflick, December 2007. An interesting and engaging editorial by famed microbiologist Leonard Hayflick explores the current scientific understanding on biological deterioration.  If you separate the prefix de, from the word generation, you find a meaning with broader connotations such as the generation of cells within our bodies that begin as one cell and degrade as many.  Multicellular organisms eventually die because as Lenard Hayflick points out, energy dispersal can never be entirely eliminated only circumvented for varying time-periods by repair or replacement processes.  This is the second law of thermodynamics which states that entropy is inevitable in closed and open systems.  The trouble with reversing entropy within multicellular organisms such as human beings is that the repair and replacement processes suffer the same fate as the cells they work to keep up and change.

[4] HarperCollins Publishers: Long For This World: The Strange Science of Immortality, Jonathan Weiner, 2010.  Science Writer Jonathan Weiner explores immortality and man’s timeless quest for conquering biological deterioration.  In 1966, Professor Gerald Gruman wrote A History of Ideas about the Prolongation of Life: The Evolution of the Prolongevity Hypothesis to 1800, in which he distinguished two types of thinkers on the issue of life and death.  The prolongevists according to Gruman are optimistic about man’s ability to extend lifespan and the apologists, who according to Weiner reconcile us to our inevitable fate.  Microbiologist Leonard Hayflick who discovered that human cells divide approximately 60 times before expiring, takes a rather sardonic position on the idea of Prolongevity saying: “Everything in the Universe changes or ages with time, and to think that you can reverse it is nonsense.”  Aubrey de Grey is of the former camp, arguing with passion and erudition that immortality is within the future anterior and molecular biology has just about zeroed in on the “causes” of cellular degeneration.  Jonathan Weiner’s book is an excellent introduction to the science of Gerontology and the individuals such as Aubrey de Grey who’re working tirelessly to supply their shoulders for tomorrow’s immoralists.

[5] IOS press: A Strategy for Postponing Aging Indefinitely, Aubrey de Grey Ph.D. 2005.

[6] New York Times Magazine: The Island Where People Forget To Die, Dan Buettner, October 24th 2012.

[7] Taylor & Francis: Rasayana: Ayurvedic herbs for longevity and rejuvenation, H.S. Puri, 2003.

[8] ELSIVIER: Pharmacology Biochemistry and Behavior: Adaptogenic effect of Bacopa Monnieri (Brahmi), Rai, Deepak; Bhatia, Gitika; Palit, Gautam; Pal, Raghwendra; Singh, Satyawan, July 1st 2003.

[9] HINDAWI: Journal of Obesity: Mindfulness Intervention for Stress Eating to Reduce Cortisol and Abdominal Fat among Overweight and Obese Women: An Exploratory Randomized Controlled Study, Jennifer DaubenmierJean KristellerFrederick M. HechtNicole ManingerMargaret KuwataKinnari JhaveriRobert H. LustigMargaret KemenyLori Karan, and Elissa Epel, June 1st 2011.

 

[10] HINDAWI: Glioprotective Effects of Ashwagandha Leaf Extract against Lead Induced Toxicity, Praveen KumarRaghavendra SinghArshed NazmiDinesh LakhanpalHardeep Kataria, and Gurcharan Kaur, May 28th2014.

 

[11] ELSIVIER: Ageing Research Reviews, Molecular Inflammation: Underpinnings of ageing and age related diseases, Chung, Hae Young, Cesari, Matteo Anton, Stephen Marzetti, Emaunuele Giovannini, Silvia, January 1st2009.

[12] ACTA, ABP, Biochimica Polonica: Curcumin and curcuminoids in quest for medical status, Grzegorz Grynkiewicz and Piotr Slifirski, May 14th 2012.

[13] WHO: World Health Organization: PERSISTANT ORGANIC POLLUTANTS (POPS) July 2008.  Persistent organic pollutants are synthetic chemicals that “persist” in the environment and bioaccumalate in fat tissue.  This why they are considered lipophilic or fat loving.

[14] NATURE Neuroscience: Cortical DNA Methylation maintains remote memory, Courtney A. MillerCristin F. GavinJason A. WhiteR. Ryley Parrish,Avinash HonasogeChristopher R. YanceyIvonne M. RiveraMaria D. RubioGavin Rumbaugh, and J. David Sweatt, June 2010.

 

This article can also be found on the Longevity Upgrades website here.

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