Hyperfunction theory of aging

The hyperfunction theory of aging, proposed by Mikhail Blagosklonny in 2006, holds that aging is driven by the continued overactivity of nutrient- and mitogen-sensing growth pathways — chiefly mTOR (mechanistic target of rapamycin) — rather than by passive accumulation of molecular damage. During development these pathways are essential for growth and reproduction; after developmental completion they are never switched off, creating a "quasi-program" — a purposeless extension of the growth program never selected against because post-reproductive harm confers no fitness penalty. The resulting cellular hyperfunction drives pathological processes such as cellular senescence, hypertrophy, fibrosis, and sterile inflammation, which produce canonical age-related diseases. The theory does not deny that molecular damage accumulates, but argues that mTOR-driven hyperfunction is life-limiting before damage alone would be. Experimental support comes from rodent studies in which rapamycin extended lifespan even when administered late in life (Harrison et al., 2009), and from a randomized trial (Mannick et al., 2014) in which low-dose everolimus improved influenza vaccine response in elderly humans. Whether mTOR inhibition translates to lifespan extension in healthy humans remains open; the PEARL trial provided preliminary safety and healthspan data in 2024 but no definitive outcome evidence as of 2025.