Longevity & AgingCaloric Restriction Slows DNA Mutation Accumulation Across Multiple Tissues in Mice
Every cell in the body accumulates DNA mutations over time — a core hallmark of aging known as genomic instability. This study in Cell used ultra-high-fidelity duplex DNA sequencing to ask whether caloric restriction (CR) could slow this process. Researchers analyzed bulk liver, bulk kidney, individual liver cells (hepatocytes), and cerebellar neurons from mice on CR diets. CR significantly reduced the total burden of both point mutations and small insertions/deletions across all tissue types tested. It also dampened the activity of a poorly understood mutational process called SBS5, which drives most spontaneous mutations in mammals. Notably, the biggest mutation-reducing effect was seen in genomically silent, transcriptionally inactive regions of the genome. The findings position diet — specifically caloric reduction — as a lever for preserving genomic integrity throughout life, adding a new mechanistic dimension to why CR extends lifespan.
