Theories of Aging

Antagonistic Pleiotropy

George Williams' evolutionary theory: genes selected for early-life benefit can be detrimental later in life, because natural selection weakens after reproductive age.

Cross-Linking Theory

Bjorksten's 1942 proposal that aging arises from progressive covalent cross-linking of structural proteins and DNA. Overlaps heavily with the AGE theory and survives as part of broader proteostasis biology.

Disposable Soma Theory

Tom Kirkwood's evolutionary theory that organisms allocate finite energy between reproduction and somatic maintenance; aging reflects the price of investing in offspring over self-repair.

Free Radical / Oxidative Stress Theory

Denham Harman's 1956 proposal that reactive oxygen species generated by metabolism progressively damage cellular macromolecules, driving aging.

Genome Maintenance Theory

Frames aging as primarily a consequence of accumulating DNA damage that overwhelms repair, driving genomic instability, senescence, stem-cell exhaustion, and disease.

Glycation & Advanced Glycation End-Products (AGEs)

The proposal that non-enzymatic glycation of long-lived proteins and DNA accumulates with chronic glucose exposure and drives age-related tissue stiffening, dysfunction, and disease.

Hormesis

The principle that a small dose of a stressor triggers an adaptive response that strengthens the organism — the unifying mechanism behind exercise, fasting, heat, cold, and many longevity interventions.

Hyperfunction Theory (Blagosklonny)

Mikhail Blagosklonny's reframing of aging as continued, inappropriate activation of growth-promoting pathways (especially mTOR) past their useful developmental window — rather than damage accumulation.

Immunological Theory of Aging

Roy Walford's idea that aging is partly driven by progressive immune-system decline and autoimmunity. Refined by modern work on immunosenescence and the senescence-associated secretory phenotype.

Inflammaging

Claudio Franceschi's framing of aging as driven by progressive, chronic, low-grade sterile inflammation. Now central to understanding most age-related diseases.

Information Theory of Aging (Sinclair)

David Sinclair's framing of aging as loss of epigenetic information, in principle recoverable through partial reprogramming.

Mitochondrial Theory of Aging

A refinement of the free-radical theory placing the mitochondrion at the centre — both as the dominant ROS source and as a target of cumulative damage.

Neuroendocrine Theory

Vladimir Dilman's framing that aging is driven by progressive loss of homeostatic regulation in the hypothalamic-pituitary axis — and that hypothalamic ‘set-point’ drift explains many age-related physiological changes.

Programmed Aging

The contested idea that aging is an evolved, actively regulated program — not a passive accumulation of damage. Increasingly defensible as molecular evidence accumulates.

Rate-of-Living Theory

Pearl's 1928 proposal that lifespan is inversely related to metabolic rate — each organism has a fixed quantity of metabolic potential to spend. Now largely refuted, but with caveats that survived as 'oxidative damage rate.'

Reliability Theory of Aging

Engineering-style framing of aging by Gavrilov and Gavrilova: organisms behave like redundant systems whose components fail randomly; aging is the depletion of redundancy until system failure.