Longevity & Anti-Aging

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Hallmarks of aging, epigenetic clocks, age reversal, senolytics, rapamycin, NAD+, caloric restriction, fasting, and longevity biotechnology.

The field of geroscience has shifted its focus from merely extending absolute lifespan to optimizing human healthspan. As global life expectancy rebounded to 73.3 years, the scientific community began looking beyond demographic myths—such as those surrounding exceptional longevity hotspots, where investigation reveals record-keeping errors and pension fraud rather than lifestyle factors—to focus on rigorous, clinical validation. This section explores the frontier of longevity biotechnology, examining the divide between evidence-based therapeutics and the marketing of premium wellness clinics.

Central to this research are pharmacological interventions targeting key nutrient-sensing pathways. Inhibiting the mTOR pathway with rapamycin has emerged as a leading strategy, with human trials evaluating its safety, dosing protocols, and benefits for neuroprotection and immune rejuvenation. Meanwhile, the metabolic regulator metformin is analyzed alongside alternatives like berberine, contrasting their effects on blood sugar, lipids, and exercise-induced adaptations. While the landmark TAME trial remains stalled, new clinical frameworks like the VITAL-H trial investigate alternative longevity candidates.

Cellular maintenance strategies form another critical pillar. This includes the clearance of senescent cells using senolytics like fisetin and quercetin, which target the biological mechanisms of aging far more effectively than traditional antioxidants. At the same time, lifestyle interventions such as continuous calorie restriction, intermittent fasting, and prolonged 36-hour fasts are evaluated for their ability to trigger autophagy and metabolic switching. However, translating preclinical success to humans remains a primary challenge. While popular NAD+ boosters like NMN and NR, along with resveratrol, effectively alter cellular markers, they lack robust clinical evidence proving they extend human lifespan. In contrast, targeted compounds like urolithin A and spermidine demonstrate clear mechanisms in promoting mitochondrial clearance and autophagy.

Finally, we examine the diagnostic tools and biological trade-offs of aging. This includes the validation of advanced epigenetic biological age clocks, such as DunedinPACE and GrimAge, which measure DNA methylation to track aging and evaluate future therapies like partial cellular reprogramming and thymic regeneration. Additionally, we analyze the biological limits of survival, the role of the gut microbiome, and the evolutionary tradeoffs between human reproduction and longevity.

68 published articles