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.
A paper which I agree with. I think somatic mutations matter, but the phenotypes are driven by problems with transcription and translation.
https://www.nature.com/articles/s43587-024-00794-x
“If somatic mutations are the fundamental driver of aging and epigenetic changes simply track this process, it’s going to be a lot harder to reverse aging than we previously thought," added co-corresponding author Steven Cummings, M.D., executive director of the San Francisco Coordinating Center at UC San Francisco and senior research scientist at Sutter Health’s California Pacific Medical Center Research Institute.
The mutations, however, are only a proportion of the methylations. It does raise an issue beyond that of mtDNA mutation, however.
https://www.biorxiv.org/content/10.1101/2025.11.23.689982v1
Our analysis reveals fundamental asymmetry across organs: post-mitotic cells such as neurons and cardiomyocytes act as critical longevity bottlenecks, with somatic mutations reducing median lifespan from a theoretical non-aging baseline of 430 years to 169 years. In contrast, proliferating tissues like liver maintain functionality for thousands of years through cellular replacement, effectively neutralizing mutation-driven decline. Multi-organ integration predicts median lifespans of 134-170 years —approximately twice current human longevity. This substantial yet incomplete reduction indicates that somatic mutations significantly drive aging but cannot alone account for observed mortality, implying comparable contributions from other hallmarks.