Revisiting the Role of Mitochondrial DNA Mutations in Aging: Bridging Theoretical Expectations with Empirical Observations

Since the association between mitochondria and aging was first identified, significant efforts have been devoted to elucidating the role of mitochondrial DNA mutations in the aging process. Due to their age-dependent accumulation, intrinsically high mutation rates, and defective replication mechanisms, mtDNA mutations have often been regarded as pivotal drivers of aging. This has led to certain intuitive yet inherently limited conclusions. Aging, however, is a multifactorial process, and the role of mtDNA cannot be simply categorized in binary terms, as its influence emerges as a composite vector of numerous interconnected physiological processes. Adopting alternative perspectives may mitigate the discrepancies between theoretical expectations and empirical findings, offering new directions and insights for future research.