Somatic mutations in aging and disease.
Level 5 - mechanism / opinion, no new human data
Narrative review without systematic search or meta-analytic pooling.
PubMed 38488948 · doi:10.1007/s11357-024-01113-3
What was done
This narrative review summarizes historical concepts and modern next-generation sequencing advancements used to quantify somatic mutations across tissues in humans, mice, and other organisms. The authors synthesize literature on cell-type-specific mutation rates, germline versus somatic differences, mutational signatures of aging and DNA repair, clonal amplification (such as clonal hematopoiesis), mitochondrial and transcriptomic mutations, and the potential causal role of somatic mutations in aging.
What was found
The abstract reports no numerical data or quantitative effect sizes. It qualitatively describes that somatic mutations accumulate irreversibly with age in normal cells and tissues across species, that somatic mutation rates differ by cell type and exceed germline rates, and that these mutations exhibit clock-like signatures and clonal expansion.
Why it matters
Clarifying how somatic mutations accumulate and clonally expand with age helps map the genomic alterations underlying age-related decline and disease vulnerability.
Limits
This is a narrative review without a systematic search protocol or quantitative meta-analysis. The abstract provides no primary sample sizes, patient counts, or effect estimates. Distinguishing causal drivers of aging from non-pathogenic passenger mutations remains an ongoing biological challenge.
Cited by
- supports As humans age, all cells throughout the body accumulate somatic mutations.