The mitochondrial theory of aging: Insight from transgenic and knockout mouse models

Youngmok C. Jang, Holly Van Remmen

Research output: Contribution to journalShort surveypeer-review

140 Scopus citations


A substantial body of evidence has accumulated over the past 35 years in support of a role for oxidative damage to the mitochondrial respiratory chain and mitochondrial DNA in the determination of mammalian lifespan. The goal of this review is to provide a concise summary of recent studies using transgenic and knockout mouse models with altered expression of mitochondrial antioxidant enzymes (MnSOD (Sod2Tg and Sod2+/-), thioredoxin 2 (Trx2+/-), mitochondrial targeted catalase (mCAT) and mutant mice models that have been genetically manipulated to increase mitochondrial deletions or mutations (PolγD257A/D257A mutant mice) to examine the role of mitochondrial oxidative stress in aging. The majority of studies using these strategies do not support a clear role for mitochondrial oxidative stress or a vicious cycle of oxidative damage in the determination of lifespan in mice and furthermore do not support the free radical theory of aging. However, several key questions remain to be addressed and clearly more studies are required to fully understand the role of mitochondria in age-related disease and aging.

Original languageEnglish (US)
Pages (from-to)256-260
Number of pages5
JournalExperimental Gerontology
Issue number4
StatePublished - Apr 2009


  • Aging
  • Mitochondria
  • Mitochondrial theory of aging
  • Oxidative stress
  • Transgenic and knockout mouse models

ASJC Scopus subject areas

  • Biochemistry
  • Aging
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Cell Biology


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