  The accumulation of somatic mutations is a driver of cancer and has long been
associated with ageing. Due to limitations in quantifying mutation burden with
age in non-cancerous tissues, the impact of somatic mutations in other ageing
phenotypes is unclear. Recent advances in DNA sequencing technologies have
allowed the large-scale quantification of somatic mutations in ageing. These
studies have revealed a gradual accumulation of mutations in most normal
tissues with age as well as a substantial clonal expansion driven mostly by
cancer-related mutations. Nevertheless, because of the relatively modest burden
of age-related somatic mutations identified so far and their stochastic nature,
it is difficult to envision how somatic mutation accumulation alone can explain
most ageing phenotypes that develop gradually. Studies across species have also
found that longer-lived species have lower somatic mutation rates, though these
could be explained by selective pressures to reduce or postpone cancer as
longevity increases. Overall, with a few exceptions like cancer, results from
recent DNA sequencing studies do not add weight to the idea that somatic
mutations with age drive ageing phenotypes and the phenotypic role, if any, of
somatic mutations in ageing remains unclear. Recent studies in patients with
somatic mutation burden and no signs of accelerated ageing further question the
role of somatic mutations in ageing.
