Deleterious mitochondrial DNA mutations accumulate in aging human tissues

Norman Arnheim, Gino A Cortopassi

Research output: Contribution to journalArticle

174 Citations (Scopus)

Abstract

This paper reviews the current state of knowledge of the contribution of mitochondrial DNA (mtDNA) mutations to the phenotype of aging. Its major focus is on the discovery of deletions of mtDNA which previously were thought to occur only in individuals with neuromuscular disease. One particular deletion (mtDNA4977) accumulates with age primarily in non-dividing cells such as muscle and brain of normal individuals. The level of the deletion rises with age by more than 1000 fold in heart and brain and to a lesser extent in other tissues. In the brain, different regions have substantially different levels of the deletion. High levels of accumulation of the deletion in tissues are correlated with high oxygen consumption. We speculate that oxidative damage to mtDNA may be 'catastrophic'; mutations affecting mitochondrially encoded polypeptides involved in electron transport could increase free radical generation leading to more mtDNA damage.

Original languageEnglish (US)
Pages (from-to)157-167
Number of pages11
JournalMutation Research DNAging
Volume275
Issue number3-6
DOIs
StatePublished - 1992
Externally publishedYes

Fingerprint

Mitochondrial DNA
Mutation
Brain
Neuromuscular Diseases
Electron Transport
Oxygen Consumption
DNA Damage
Free Radicals
Phenotype
Muscles
Peptides

Keywords

  • Human tissue
  • Mitochondrial DNA
  • Mitochondrial DNA deletion

ASJC Scopus subject areas

  • Aging
  • Genetics
  • Molecular Biology

Cite this

Deleterious mitochondrial DNA mutations accumulate in aging human tissues. / Arnheim, Norman; Cortopassi, Gino A.

In: Mutation Research DNAging, Vol. 275, No. 3-6, 1992, p. 157-167.

Research output: Contribution to journalArticle

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