Mitigation of age-dependent accumulation of defective mitochondrial genomes.

ABSTRACT: Unknown processes promote the accumulation of mitochondrial DNA (mtDNA) mutations during aging. Accumulation of defective mitochondrial genomes is thought to promote the progression of heteroplasmic mitochondrial diseases and degenerative changes with natural aging. We used a heteroplasmic Drosophila model to test 1) whether purifying selection acts to limit the abundance of deleterious mutations during development and aging, 2) whether quality control pathways contribute to purifying selection, 3) whether activation of quality control can mitigate accumulation of deleterious mutations, and 4) whether improved quality control improves health span. We show that purifying selection operates during development and growth but is ineffective during aging. Genetic manipulations suggest th

SUBMITTER: Tsai PI 

PROVIDER: S-EPMC9351377 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature