Medical Interventions for Human Life Span Extension
Compounds like resveratrol spermidine, rapamycin and metformin may slow aging, but more human studies are needed.
Blurb: Life extension research is advancing, with compounds like resveratrol, metformin, spermidine, and rapamycin showing promise in delaying aging. These agents target cellular repair, inflammation, and metabolic balance, though large-scale human studies are still needed. While full reversal of aging is unlikely, slowing its progress holds potential for healthier, longer lives.
Introduction
The prospect of increasing human life span is exciting; it remains an existential concern and an eternal quest. Exercise, diet, lifestyle, and genetics play a limited role in extending the human life span. There is an exponential demand for a therapeutic agent to delay aging and promote life extension. Aging is complex and multidimensional. However, we do not have suitable laboratory animals to replicate human aging. Further, experiments on such surrogate models can be fraught with aberrant results or artifacts. Extrapolating such inferences to human lifespan research can be deleterious. With the current state of molecular and medical understanding, we may slow down the process of aging. However, complete reversal and unrealistic lifespan increases may not be possible. Among the repertoire of drugs available for human use, a handful of agents have shown promising results in decelerating aging.
Antioxidant Supplement
Resveratrol, a potent antioxidant and an active ingredient of red wine, downregulates inflammatory and oxidative stress, reduces atherogenesis, and alters gene expression favorably. Similarly, polyphenols and flavonoids in brightly colored citrus fruits, pomegranates, cherries, and berries can also play a beneficial role in delaying aging. Populations that regularly consume several servings of these fruits, their juices, or wine have a higher number of centenarians. Resveratrol in red wine can activate Sirtuin 1 (an antiaging protein) that plays a vital role in DNA repair and containing inflammation. Activation of such pathways can substantially increase human life span due to repair and restoration. Compounds like resveratrol from red wine are available as capsule supplements without the sugar or alcohol content of the wine.
Diabetic Medication
Metformin is an oral biguanide, a well-known diabetic medication used universally. It has increased the life span of laboratory rodents. Metformin can target age-related degeneration and chronic diseases; thereby, it could have an indirect effect on the improvement of life span. Primarily, metformin increases insulin sensitivity and ensures stable blood sugar levels. In addition to that, metformin retards cellular aging in the laboratory worm model Caenorhabdytis elegans. Metformin activates AMPK, a protein enzyme responsible for fat metabolism and metabolic homeostasis (balance). Preliminary studies with metformin in the diabetic population have shown a decrease in age-related degenerative diseases, stroke, dementia, cancer, and cognitive decline. However, large-scale results are awaited.
Spermidine Supplement
Spermidine, a polyamine found in semen and many plants, improves cell repair and induction of autophagy. Aging can result in the accumulation of cellular debris, protein aggregates, chronic inflammation, and poor immunity. Autophagy is a process in which cells and their contents break down and remove dysfunctional components. Autophagy is essential in preventing aging; any intervention that increases autophagy can inhibit the acceleration of aging. Spermidine (available as a supplement) may counteract the ill effects of aging and thereby improve the quantum and quality of life.
Immunosuppressive Medication
Rapamycin, or Sirolimus is a well-known immunosuppressive medication used in transplants, cancer, and autoimmune disorders. Extracted from the soil bacteria of the Easter Islands, rapamycin has proved to be invaluable in the fields of transplantation and cancer therapeutics. Rapamycin inhibits mTOR (Mammalian Target of Rapamycin), which is a protein kinase enzyme that controls cellular activity, autophagy, repair, and movement. Dysregulation of mTOR is associated with several human degenerative diseases, tumor formation, cancer, neurodegeneration, and aging. In laboratory animals, microbes, and mammals, rapamycin downregulates cellular senescence (aging), improves life span, and delays age-related complications. Decreasing Mtor signaling can improve lifespan and prevent chronic diseases. In theory, regular consumption of rapamycin can retard aging significantly. However, what prevents a full-scale recommendation of its use is the range of side effects exhibited by the drug.
Conclusion
Life span research is progressing at a rapid pace. There is unraveling of a few novel pathways, and the results of preliminary studies are encouraging. However, aging is multifactorial, and therapeutic efforts to modulate it are in their early stages. Meanwhile, the compounds mentioned above have shown promise at the laboratory level and in some population studies. In the race to reset our genetic clock, we may discover molecules that could significantly extend our life span.
Gifty Immanuel MD,PhD,FRCP, FIDSA
Medical Director, Synergia
References
Harrison, T. R. (2021). Harrison’s principles of internal medicine (J. Loscalzo, A. S. Fauci, D. L. Kasper, S. L. Hauser, D. L. Longo, & J. L. Jameson, Eds.; 21st edition). McGraw-Hill Education.
Cabreiro, F., Au, C., Leung, K. Y., Vergara-Irigaray, N., (2013). Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism. Cell, 153(1), 228–239.
Hofer, S. J., Daskalaki, I., Bergmann, M., Friščić, J., Zimmermann, A (2024). Spermidine is essential for fasting-mediated autophagy and longevity. Nature cell biology, 26(9), 1571–1584.
Lee, D. J. W., Hodzic Kuerec, A., & Maier, A. B. (2024). Targeting ageing with rapamycin and its derivatives in humans: a systematic review. The lancet. Healthy longevity, 5(2), e152–e162.
