The free-radical theory of ageing--older, wiser and still alive: modelling positional effects of the primary targets of ROS reveals new support

Bioessays. 2012 Aug;34(8):692-700. doi: 10.1002/bies.201200014. Epub 2012 May 29.


The continuing viability of the free-radical theory of ageing has been questioned following apparently incompatible recent results. We show by modelling positional effects of the generation and primary targets of reactive oxygen species that many of the apparently negative results are likely to be misleading. We conclude that there is instead a need to look more closely at the mechanisms by which free radicals contribute to age-related dysfunction in living systems. There also needs to be deeper understanding of the dynamics of accumulation and removal of the various kinds of molecular damage, in particular mtDNA mutations. Finally, the expectation that free-radical damage on its own might cause ageing needs to be relinquished in favour of the recognition that the free-radical theory is just one of the multiple mechanisms driving the ageing process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Aging / physiology
  • Animals
  • Antioxidants / metabolism
  • DNA Damage
  • DNA, Mitochondrial / genetics
  • DNA, Mitochondrial / metabolism*
  • Mitochondria / genetics
  • Mitochondria / physiology
  • Mitochondrial Membranes / metabolism
  • Models, Molecular
  • Mole Rats / metabolism
  • Mole Rats / physiology
  • Mutation
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism*
  • Selection, Genetic


  • Antioxidants
  • DNA, Mitochondrial
  • Reactive Oxygen Species