Stochastic survival of the densest and mitochondrial DNA clonal expansion in aging.

ABSTRACT: The expansion of mitochondrial DNA molecules with deletions has been associated with aging, particularly in skeletal muscle fibers; its mechanism has remained unclear for three decades. Previous accounts have assigned a replicative advantage (RA) to mitochondrial DNA containing deletion mutations, but there is also evidence that cells can selectively remove defective mitochondrial DNA. Here we present a spatial model that, without an RA, but instead through a combination of enhanced density for mutants and noise, produces a wave of expanding mutations with speeds consistent with experimental data. A standard model based on RA yields waves that are too fast. We provide a formula that predicts that wave speed drops with copy number, consonant with experimental data. Crucially, our model yiel

SUBMITTER: Insalata F 

PROVIDER: S-EPMC9894218 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature