The multi-tissue landscape of somatic mtDNA mutations indicates tissue-specific accumulation and removal in aging.

ABSTRACT: Accumulation of somatic mutations in the mitochondrial genome (mtDNA) has long been proposed as a possible mechanism of mitochondrial and tissue dysfunction that occurs during aging. A thorough characterization of age-associated mtDNA somatic mutations has been hampered by the limited ability to detect low-frequency mutations. Here, we used Duplex Sequencing on eight tissues of an aged mouse cohort to detect >89,000 independent somatic mtDNA mutations and show significant tissue-specific increases during aging across all tissues examined which did not correlate with mitochondrial content and tissue function. G→A/C→T substitutions, indicative of replication errors and/or cytidine deamination, were the predominant mutation type across all tissues and increased with age, whereas G→T/C→A subst

SUBMITTER: Sanchez-Contreras M 

PROVIDER: S-EPMC10072880 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature