Longevity medicine — targeting the biological processes of aging rather than individual diseases — has moved from fringe geroscience to mainstream clinical interest with the 2023 Lopez-Otin et al. expansion of the hallmarks of aging to 12 interconnected cellular and molecular processes. Understanding which interventions have genuine evidence, which are biologically plausible but unproven in humans, and which are marketing-driven speculation separates evidence-based longevity practice from the $5 billion supplements industry.
The 12 Hallmarks of Aging
The current framework (2023): genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy (new), deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation (inflammaging), and dysbiosis (new). These hallmarks are interconnected — genomic instability drives senescence; senescence drives inflammaging; inflammaging accelerates all other hallmarks. The framework guides drug target identification: senolytic drugs target senescent cells, rapamycin targets mTOR (nutrient sensing), NAD+ precursors target mitochondrial function and sirtuin activation, metformin targets AMPK (energy sensing).
Evidence for Specific Interventions
Metformin (TAME trial ongoing): compelling epidemiological evidence (diabetics on metformin live longer than non-diabetics not on metformin in observational data). TAME (Targeting Aging with Metformin) trial — first FDA-approved trial with aging itself as an endpoint — will provide definitive human evidence. Currently: reasonable safety profile, accessible, biologically plausible — but unproven for lifespan extension in non-diabetic humans. Rapamycin (mTOR inhibitor): extends lifespan in multiple organisms including mice — the strongest mammalian evidence for any pharmacological intervention on lifespan. Human clinical trials in aging are beginning. Current use is off-label; side effects (immunosuppression, metabolic effects) require medical supervision. NAD+ precursors (NMN, NR): restore NAD+ levels that decline with age; activate sirtuins and support DNA repair and mitochondrial function. Human trials show NAD+ levels increase with supplementation — functional longevity benefits not yet proven in RCTs. Senolytics (dasatinib + quercetin): phase 2 trials showing reduced senescent cell burden and improved physical function in older adults — the most advanced class of true anti-aging therapeutic. Lifestyle interventions with strongest evidence: caloric restriction (consistent lifespan extension in all studied organisms, mimicked by intermittent fasting in rodents, metabolic benefits in humans), exercise (the single best-supported intervention for healthspan in humans), and not smoking. For clinical preventive medicine programs, our diagnostic equipment section and lab supplies support comprehensive metabolic and biomarker monitoring.
