Membrane fatty acid unsaturation, protection against oxidative stress, and maximum life span: a homeoviscous-longevity adaptation?

Ann N Y Acad Sci. 2002 Apr;959:475-90. doi: 10.1111/j.1749-6632.2002.tb02118.x.


Aging is a progressive and universal process originating endogenously that manifests during postmaturational life. Available comparative evidence supporting the mitochondrial free radical theory of aging consistently indicates that two basic molecular traits are associated with the rate of aging and thus with the maximum life span: the presence of low rates of mitochondrial oxygen radical production and low degrees of fatty acid unsaturation of cellular membranes in postmitotic tissues of long-lived homeothermic vertebrates in relation to those of short-lived ones. Recent research shows that steady-state levels of free radical-derived damage to mitochondrial DNA (mtDNA) and, in some cases, to proteins are lower in long- than in short-lived animals. Thus, nonenzymatic oxidative modification of tissue macromolecules is related to the rate of aging. The low degree of fatty acid unsaturation in biomembranes of long-lived animals may confer advantage by decreasing their sensitivity to lipid peroxidation. Furthermore, this may prevent lipoxidation-derived damage to other macromolecules. Taking into account the fatty acid distribution pattern, the origin of the low degree of membrane unsaturation in long-lived species seems to be the presence of species-specific desaturation pathways that determine membrane composition while an appropriate environment for membrane function is maintained. Mechanisms that prevent or decrease the generation of endogenous damage during the evolution of long-lived animals seem to be more important than trying to intercept those damaging agents or repairing the damage already inflicted. Here, the physiological meaning of these findings and the effects of experimental manipulations such as dietary stress, caloric restriction, and endocrine control in relation to aging and longevity are discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / physiology
  • Animals
  • Dietary Fats
  • Fatty Acids, Unsaturated / chemistry
  • Fatty Acids, Unsaturated / metabolism*
  • Humans
  • Life Expectancy
  • Lipid Peroxidation
  • Longevity*
  • Membrane Lipids / chemistry
  • Membrane Lipids / metabolism*
  • Mitochondria, Heart / metabolism
  • Models, Biological
  • Oxidative Stress*
  • Reactive Oxygen Species / metabolism


  • Dietary Fats
  • Fatty Acids, Unsaturated
  • Membrane Lipids
  • Reactive Oxygen Species