Life Extension Magazine®

DNA of cell being supported by withaferin A supplement

Novel Healthy Longevity Strategy

Aging results in altered cell-to-cell signaling that causes systemic degeneration. Utilizing deep-learning artificial intelligence, scientists have identified a method to restore more youthful cell signaling. This may facilitate leaner body mass, improved cognition, reduced inflammation, more youthful gene expression, and improved cell protein stability.

Scientifically reviewed by Dr. Gary Gonzalez, MD, in August 2023. Written by: William Faloon.

William Faloon
William Faloon

We live in an unprecedented era as it relates to our understanding of the fundamental causes of biological aging.

This knowledge enables us to investigate and measure the effectiveness of interventions that may enable meaningful reversals of degenerative processes.

The enthusiasm surrounding the prospect of systemic rejuvenation has not gone unnoticed. Headline news reports on today’s billionaires who are funding projects aimed at achieving longer human healthspans.1-9

We at Life Extension® applaud all those seeking to turn aging into a relic of the past, as was done with smallpox, polio, and other diseases.

What makes aging different are the multiple biological and environmental factors involved. It is unlikely any one person will discover the ultimate cure.

Aging creates an alteration of signals that cells emit to enable youthful functionality. The impact of disrupted cell signaling is senile degeneration, along with unwanted body fat stores.

Until recently, little could be done to mitigate this malfunction of cell-to-cell signaling.

I’m pleased to announce that a group of scientists, utilizing deep-learning artificial intelligence, has identified a method we can utilize today to restore more youthful cell signaling.

Based on published laboratory results, this new approach may facilitate leaner body mass, improved cognition, reduced inflammation, more youthful gene expression and improved cell-protein stability.

What you need to know

Substantial advances have been made in the technology around artificial intelligence, which have allowed us to identify complex mechanisms that delay aging. A compound that has been shown to work by some of these mechanisms has been identified as an extract from the ashwagandha herb. Together with other compounds, multiple pathways can be targeted to delay several aspects of aging.

Youthful Cell Signaling Prompts Weight Loss

Image with Caption
Fat cells from adipose
tissue (adipocytes).

In youth, our cells emit signals that enable them to function at peak performance.10

As we age, youthful cell signaling declines.

One effect of restoring healthy cell signaling is a reduction in excess fat storage.

This was demonstrated in a study published in 2016, where supplementing with a novel plant extract resulted in a 20%-25% reduction of body weight in diet-induced obese mice.

A mechanism that prompted this beneficial effect was sensitizing brain cells to leptin, a hormone that induces satiety.11

Fat cells secrete leptin to tell our brains we are full after we eat.

In states of obesity and advanced age, leptin receptors in the brain become desensitized to the satiety signals sent out by our fat cells. The result is we eat too much and store excess energy as fat.

In response to a concentrated extract from ashwagandha, a group of obese mice ate less food (compared to controls) and subsequently lost substantial weight.11

The name of the extract used in this weight-loss study is withaferin A.

Compared to commercially available ashwagandha supplements, this novel withaferin A provides a 7.5-fold greater concentration.

Research into withaferin A is yielding a treasure trove of additional health benefits.

The effects induced by withaferin A include suppression of inflammatory factors while upregulating genes that protect against abnormal fat storage.11-13

Delay of Brain Aging

Normal aging results in loss of brain cell function and structure.14

This manifests outwardly as mild cognitive impairment and loss of motor coordination that can progress to dementia.14,15

A study was done on mice genetically programmed to develop loss of neuronal (brain cell) function.16

Supplementation with withaferin A was started before the onset of neuronal dysfunction.16 Compared to controls, the withaferin A group showed:

  1. Alleviation of neuro-inflammation
  2. Decreased levels of misfolded protein in the spinal cord by 39%
  3. Reduced loss of motor neurons by more than 60%
  4. Delayed progression of neuronal dysfunction
  5. Extension of lifespan

These findings are pertinent to people who have not yet experienced significant cognitive impairment, but may also be relevant to elderly individuals.

Overcoming a Limit on Maximum Lifespan

Withaferin A is an exceptionally active plant compound with a broad range of actions. These actions include favorably targeting proteins in our body that are structurally distorted by normal aging and are linked to degenerative conditions.11,16,17

By restoring youthful cell protein stability, a number of challenging limitations we face with lifespan potential can be ameliorated.17

For example, our cells survive via a process that involves precise folding of new proteins into cellular components, along with removal of damaged cell proteins.17

Aging causes “misfolding” of cellular proteins and an inability to degrade damaged proteins that accumulate inside cells.18,19

A limitation on maximal life-span is loss of youthful protein function.18

Proteostasis” is a term you’re going to start hearing a lot about. Youthful proteostasis involves the optimal synthesis, folding, and removal of proteins inside cells.17

As healthy proteostasis declines, cells become dysfunctional and chronic diseases develop.19

Withaferin A impedes cell protein misfolding that is linked to a number of age-related issues.11-13,16,17

We Fought Against This Aging Pathology in the 1980s

In the 1980s, Life Extension Foundation funded research at the Florida Institute of Technology to circumvent the decline in protein synthesis that occurs with normal aging.20-29

Before the first mouse study was completed, the lead scientist succumbed to heart failure and had to retire. I thought back then how ironic it was that a brilliant scientist seeking to circumvent aging was himself taken out by a degenerative illness.

This is one of many reasons why I am working around the clock to accelerate human age-reversal research. If we don’t enable scientists today to carry out their work, they will age to death and we lose forever their internal library of brilliance.

The Florida Institute of Technology is a research university with academic divisions that emphasizes science, engineering, mathematics, and aviation. Here are Life Extension articles from the 1980s that discuss the role of protein synthesis and aging:

• “Genetic Control Mechanisms and Aging; Control of Protein Synthesis. Anti-Aging Conference Report Part II.” Anti-Aging News. 1985 Feb;5(2):16.

• “Protein Synthesis & Aging – George C Webster, PhD. Florida Institute of Technology. The Life Extension Breakthrough Conference.” Anti-Aging News. 1985 Sep;5(9)106.

• “First Project 2000 Grants to Extend the Human Lifespan. Unraveling the Mystery of Protein Synthesis; Decrease in Protein Synthesis with Age.” Anti-Aging News. 1985 Nov;5(11):122.

• “The Life Extension Breakthrough Conference. Restoring Youthful Levels of Protein Synthesis.” Life Extension Report. 1986 Jul;6(7):78.

(Note in years 1980-1985 the name of our scientific publication was Anti-Aging News. It was changed to Life Extension Report in 1986 and then Life Extension Magazine in 1994.)

Activating Cell-Signaling Pathways

Life Extension® has partnered with a company called Insilico Medicine to evaluate plant extracts that confer longevity effects as identified in recent scientific studies.30

The first step utilizing deep-learning artificial intelligence enabled Insilico Medicine to uncover specific cell-signaling pathways that confer longevity when activated.30

Insilico Medicine then used their proprietary A.I. technology to score compounds based on their cumulative activation of known anti-aging pathways.

The Insilico analysis reveals three extracts that together scored the best out of thousands of ingredients and their combinations.30

This enabled Insilico Medicine to patent a combination of three natural extracts in a formula designed to promote healthy aging.

The Insilico formula contains highly-standardized withaferin A and ginsenoside Rg3 extracts along with concentrated gamma linolenic acid.

The tradename of this formula is Longevity A.I.™. The box below shows how potent the ingredients are:

Longevity AI  

Note the concentrations of active ingredients in the Longevity A.I.™ are several magnitudes higher than conventional dietary supplements.

The initial cost of these highly-standardized botanical ingredients is relatively high, but we anticipate price reductions as greater volumes reduce costs.

The dose of the new Longevity A.I.™ formula is one softgel daily.

Be the First to Discover Healthy Aging…

Discover Healthy Aging  

Life Extension readers are often the first to learn about validated methods to protect against degenerative aging.

Our track record of translating research findings into practical approaches dates back to the early 1980s.

We’ve entered a new phase of accelerated development utilizing deep-learning artificial intelligence to identify better methods to combat degenerative processes.

This enhanced ability to validate novel approaches to wellness is enabling us to rapidly design formulas to stave off degenerative changes at the cellular level.

These advances are essential if we are to remain alive long enough to benefit from the age-reversal research initiatives that your supplement purchases are helping to fund today.

For a scientific report on the deep-learning artificial intelligence described in this editorial, please turn to page 52 of this month’s issue.

For longer life,

For Longer Life

William Faloon, Co-Founder
Life Extension Buyers Club


  1. Available at: Accessed April 12, 2017.
  2. Available at: Accessed April 12, 2017.
  3. Available at: Accessed April 12, 2017.
  4. Available at: Accessed April 12, 2017.
  5. Available at: Accessed April 12, 2017.
  6. Available at: Accessed April 12, 2017.
  7. Available at: Accessed April 12, 2017.
  8. Available at: Accessed January 29, 2018.
  9. Available at: Accessed April 12, 2017.
  10. Lopez-Otin C, Blasco MA, Partridge L, et al. The hallmarks of aging. Cell. 2013;153(6):1194-217.
  11. Lee J, Liu J, Feng X, et al. Withaferin A is a leptin sensitizer with strong antidiabetic properties in mice. Nat Med. 2016;22(9):1023-32.
  12. Kanak MA, Shahbazov R, Yoshimatsu G, et al. A small molecule inhibitor of NFkappaB blocks ER stress and the NLRP3 inflammasome and prevents progression of pancreatitis. J Gastroentero l. 2017;52(3):352-65.
  13. Palliyaguru DL, Chartoumpekis DV, Wakabayashi N, et al. Withaferin A induces Nrf2-dependent protection against liver injury: Role of Keap1-independent mechanisms. Free Radic Biol Med. 2016;101:116-28.
  14. Nyberg L, Lovden M, Riklund K, et al. Memory aging and brain maintenance. Trends Cogn Sci. 2012;16(5):292-305.
  15. Seidler RD, Bernard JA, Burutolu TB, et al. Motor control and aging: links to age-related brain structural, functional, and biochemical effects. Neurosci Biobehav Rev. 2010;34(5):721-33.
  16. Patel P, Julien JP, Kriz J. Early-stage treatment with Withaferin A reduces levels of misfolded superoxide dismutase 1 and extends lifespan in a mouse model of amyotrophic lateral sclerosis. Neurotherapeutics. 2015;12(1):217-33.
  17. Balch WE, Morimoto RI, Dillin A, et al. Adapting proteostasis for disease intervention. Science. 2008;319(5865):916-9.
  18. Ben-Zvi A, Miller EA, Morimoto RI. Collapse of proteostasis represents an early molecular event in Caenorhabditis elegans aging. Proc Natl Acad Sci U S A. 2009;106(35):14914-9.
  19. Morimoto RI, Cuervo AM. Proteostasis and the aging proteome in health and disease. J Gerontol A Biol Sci Med Sci. 2014;69 Suppl 1(Suppl 1):S33-8.
  20. Gregory M. Fahy P. Genetic Control Mechanisms and Aging. Control of Protein Synthesis. Anti-Aging Conference Report Part II. Anti-Aging News. 1985;5(2):16.
  21. First Project 2000 Grants to Extend the Human Lifespan. Unraveling the Mystery of Protein Synthesis; Decrease in Protein Synthesis with Age. Anti-Aging News. 1985;5(11):121.
  22. Kent S. Protein Synthesis & Aging – George C Webster, PhD. Florida Institute of Technology. The Life Extension Breakthrough Conference. Anti-Aging News. 1985;5(9):106.
  23. The Life Extension Breakthrough Conference. Restoring Youthful Levels of Protein Synthesis. Life Extension Report. 1986;6(7):78.
  24. Kent S. New Life Extension Studies. Inducing Muscle Generation. Life Extension Report. 1986;6(11):123.
  25. Webster GC, Beachell VT, Webster SL. Differential decrease in protein synthesis by microsomes from aging Drosophila melanogaster. Exp Gerontol. 1980;15(5):495-7.
  26. Webster GC, Webster SL, Landis WA. The effect of age on the initiation of protein synthesis in Drosophila melanogaster. Mech Ageing Dev. 1981;16(1):71-9.
  27. Webster GC, Webster SL. Effects of age on the post-initiation stages of protein synthesis. Mech Ageing Dev. 1982;18(4):369-78.
  28. Webster GC, Webster SL. Decline in synthesis of elongation factor one (EF-1) precedes the decreased synthesis of total protein in aging Drosophila melanogaster. Mech Ageing Dev. 1983;22(2):121-8.
  29. Webster GC, Webster SL. Specific disappearance of translatable messenger RNA for elongation factor one in aging Drosophila melanogaster. Mech Ageing Dev. 1984;24(3):335-42.
  30. Aliper A, Jellen L, Cortese F, et al. Towards natural mimetics of metformin and rapamycin. Aging (Albany NY). 2017;9(11):2245-68.