Early-life mitochondrial DNA mutations drive age-related pathology in mice

In a new preprint, researchers engineered mice to confine mitochondrial DNA mutagenesis to specific developmental windows. The authors found that mitochondrial mutations acquired during the first two months of life were sufficient to trigger diverse age-related pathologies later in adulthood. The severity of these diseases depended on distinct, tissue-specific selective pressures that determined which mutations persisted or expanded over time. Furthermore, the team demonstrated that altering mitochondrial fusion, both in vitro and in vivo, modified the selection against these harmful genetic variants. These findings show that early-life mutational events can establish the trajectory of tissue aging in mice, while mitochondrial dynamics can directly influence the survival of pathogenic variants.