Mutation accumulation theory

Mutation accumulation theory is an evolutionary explanation for why you age. Peter Medawar first proposed it in his 1952 lecture, 'An Unsolved Problem of Biology.' The core idea: mutations that only do harm late in life, after your peak reproductive years, slip past natural selection and pile up over generations. That is because selection weakens with age. A mutation that kills you before you reproduce gets purged. One that only hurts you after reproduction lingers, in what Medawar called the 'selection shadow.' Genetic drift can then push it to high frequency, eroding function in older people. Charlesworth (2001) turned this into a quantitative model. It predicts that the genetic variance in age-specific death rates rises exponentially with age, which fits human and fruit-fly data. Turan et al. (2019) added molecular evidence. They found that gene activity becomes less conserved with age (a pattern they called ADICT) across 16 tissues in five mammal species, with late-expressed genes under weaker selection and tied to cell-death and inflammation pathways. This theory differs from antagonistic pleiotropy: it needs no early-life benefit, just late-life harm. Which mechanism dominates for a given trait is still unresolved.

Last reviewed: June 22, 2026

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