Celebrate the Facts!
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Since the dawn of consciousness, humans have been searching for magical compounds and techniques to extend what can never be replaced - a person’s time on this planet. Many techniques, such as extended fasting, vitamin supplementation, exercise, and now pharmaceutical compounds, are tools to extend life, both lifespan and quality of life. One of these, rapamycin, has hit the mainstream, and doctors routinely prescribe it as a longevity drug despite incomplete evidence of its efficacy. Human life expectancy constantly rises, and the median lifespan increases, but the maximum lifespan does not. Although the number of centenarians (100 or older) doubles every ten years, maximum longevity remains the same. The longest-living person died in 1997 at 122; this record has not been beaten. Researchers first isolated rapamycin from soil samples collected from Easter Island in the 1960s. This exciting find contained streptomyces hygroscopicus, a bacteria native to the island. Realizing that streptomyces hygroscopicus produced a compound that could kill fungi, they named it rapamycin after the island, Rapa Nui. When scientists discovered rapamycin inhibited the growth of eukaryote cells, research on rapamycin turned to rapamycin’s immunosuppressive and anticancer properties. A eukaryote is any cell or organism that possesses a clearly defined nucleus. The United States Food and Drug Administration (FDA) approved rapamycin in 1994 to help prevent organ rejection in liver transplant patients, marking a significant milestone in organ transplantation. Rapamycin is also used to avoid restenosis after coronary angioplasty, and it is being tested in many clinical trials as an antitumor agent. That research paid off when the FDA approved the use of rapamycin for treating pancreatic cancer patients in 2011. In 1994, several scientists independently discovered several aspects of rapamycin’s mechanism of action. When rapamycin crosses a cell membrane and enters a cell, it binds with an enzyme named mTOR, the mechanistic target of rapamycin. In doing so, rapamycin partially inhibits mTOR activity, which enables the activation of autophagy. Rebalancing the mTOR/autophagy ratio may result in extraordinary vigor upgrades and pause aging initiation. In 2009, researchers found rapamycin could increase the lifespan of mice when administered later in life. This was the first evidence that a pharmacologic agent could lengthen life. Since then, there has been a surge in research investigating the effects of rapamycin on various diseases, biological functions, and organic processes in mice. However, the importance of further human studies to validate these effects cannot be overstated, underscoring the urgency and importance of our continued exploration in this promising field. Popular theory considers pharmaceuticals as the primary means of delaying aging. Over the past decades, various anti-aging drugs, such as the mTOR inhibitor rapamycin; antioxidants such as resveratrol, melatonin, and coenzyme Q10 (CoQ10); and especially senolytics such as dasatinib and quercetin (D + Q) or fisetin, have shown promising effects on longevity by targeting mTOR, mitochondrial and oxidative stress, and cellular senescence. When nutrients are available to a cell, mTOR initiates signals that activate cell metabolism, telling the cell to use the available nutrients to build new proteins, enzymes, and other cell components. mTOR is a crucial sensor of nutrient availability. When nutrients are available, mTOR activates cell anabolic (building) growth and proliferation processes. Autophagy is a process within all cells that counterbalances mTOR’s activities. It occurs when the body breaks down damaged proteins, enzymes, and other cell components for reuse or elimination. Most cells contain hundreds of mTOR sites. When a person takes rapamycin, it enters cells and binds to some mTOR sites. This results in partial inhibition of mTOR and the activation of autophagy, which promotes a wide range of health benefits in people constantly over-activating mTOR (most people). Inhibiting mTOR and activating autophagy allows all cells in the body to detoxify more effectively and undergo regeneration and restoration. Results from animal models suggest that partially inhibiting mTOR with rapamycin might improve symptoms of continuing progressive diseases. This category includes metabolic syndrome and Type 2 diabetes, inflammatory conditions like arthritis and lupus, nerve ailments such as Parkinson’s and multiple sclerosis, macular degeneration, glaucoma, obesity, hearing loss, periodontal disease, cognitive decline, and Alzheimer’s disease. Obesity is an escalating global health crisis with direct links to metabolic syndrome and cardiovascular disease. Because rapamycin inhibits mTOR, it mimics calorie restriction. In animal studies, rapamycin therapy decreases appetite and reduces body weight and fat mass. Based on these results, rapamycin might be a potential tool for obesity treatment. Proponents point to rapamycin's benign side effect profile, which includes a variety of conditions like many other drugs. As physicians use the drug for various situations, including mitigating transplant rejection, scientists have closely defined these side effects, providing a risk profile for examination by physicians and potential users of the drug. It is almost certain that the FDA will never approve rapamycin for longevity. The agency doesn’t categorize aging as a disease, plus rapamycin’s generic status means there’s little financial incentive to run expensive clinical trials for aging or similar ailments.
Living a healthy and long life is achievable, provided genetic medical conditions are manageable and lifestyle conditions are healthy and supportive of such ambitions. The mix includes emotional wellness, sleep, exercise, diet, and environmental factors. Pills alone may support this endeavor, but they are in no way a magic bullet. Instead, they could help boost health and longevity. Unfortunately, the science about the efficacy and risks of longevity compounds, including rapamycin, is murky and unlikely to be resolved soon. Still, the temptation exists, particularly for older people who don’t wish to wait and choose to be their laboratory rat.
1 Comment
terri
7/24/2024 11:22:07 am
Interesting stats. Finally done with 3 yrs at Emory and staying on Student Health for an extra 6 monhs to address some of these issues. Thank you
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InvestigatorMichael Donnelly investigates societal concerns with an untribal approach - to limit the discussion to the facts derived from primary sources so the reader can make more informed decisions. Archives
January 2025
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