It is widely accepted that stochastic nuclear DNA damage plays a significant role in cancer development, but its contribution to degenerative aging is still a topic of debate. Mutations in inactive regions of DNA may accumulate in cells with limited divisions left, potentially impacting tissue function. One theory suggests that somatic mosaicism, the spread of mutations in tissue, could lead to subtle dysfunctions over time. Another theory focuses on the unintended consequences of DNA repair machinery operation, which may alter epigenetic control and gene expression with age. Recent DNA sequencing studies reveal an increase in mutations with age, consistent with cancer risk, but the relationship with aging phenotypes remains unclear. Evolutionary pressures to prevent cancer may limit the number of mutations that contribute to age-related conditions. While some inherited mutations do not result in accelerated aging, the impact of somatic mutations, copy-number alterations, and structural variations on aging phenotypes requires further investigation.
Despite advancements in genetics and genomics, empirical evidence linking somatic mutations to aging remains elusive, raising doubts about their primary role in the aging process. The debate continues as researchers strive to understand the complex relationship between nuclear DNA damage, mutations, and age-related dysfunction.
