Ageing and the free radical theory

Respir Physiol. 2001 Nov 15;128(3):379-91. doi: 10.1016/s0034-5687(01)00313-9.


The free radical theory proposes that ageing is the cumulative result of oxidative damage to the cells and tissues of the body that arises primarily as a result of aerobic metabolism. Several lines of evidence have been used to support this hypothesis including the claims that: (1) variation in species life span is correlated with metabolic rate and protective antioxidant activity; (2) enhanced expression of antioxidative enzymes in experimental animals can produce a significant increase in longevity; (3) cellular levels of free radical damage increases with age; and (4) reduced calorie intake leads to a decline in the production of reactive oxygen species and an increase in life span. The free radical theory may also be used to explain many of the structural features that develop with ageing including the lipid peroxidation of membranes, formation of age pigments, cross-linkage of proteins, DNA damage and decline of mitochondrial function. Despite this, many uncertainties concerning the role of oxidative damage in ageing remain and alternative explanations cannot be ruled out. Free radicals only occur in trace quantities in biological tissues, their cellular levels and actions cannot be measured in vivo, and definitive proof that oxidised molecules are the primary cause of ageing is lacking. Moreover, ageing is also likely to be a multifactorial process and not reducible to any one single cause. Thus, despite its positive features, the evidence for the free radical theory is either correlative or inconclusive.

Publication types

  • Review

MeSH terms

  • Aging / metabolism*
  • Animals
  • Antioxidants / metabolism
  • Energy Metabolism / physiology
  • Free Radicals / metabolism*
  • Humans
  • Reactive Oxygen Species / metabolism*


  • Antioxidants
  • Free Radicals
  • Reactive Oxygen Species