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Free-radical Theory of Aging

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Free-radical Theory of Aging

Authors:

D. Harman and N. M. Emanuel.

History:

This theory was suggested nearly simultaneously by D. Harman in 1956 and N. M. Emanuel in 1958. Last years, it is one of the fundamental theories of aging which develops actively.

Example:

In some model organisms, such as yeast and Drosophila, there is evidence that reducing oxidative damage can extend lifespan. In mice, interventions that enhance oxidative damage generally shorten lifespan.

Description of the Theory:

According to this theory, free radicals — reactive oxygen species (ROS) — are the main origin of aging by causing oxidative cellular injuries. Free radicals are necessary for many biochemical processes and they are produced as by-products during some biochemical reactions or as substrates for other biochemical reactions in each cell.

If an aggressive, chemically reactive free radical leaves that place where it is necessary, it can damage DNA, as well as RNA, proteins and lipids. Peroxidation is extremely dangerous for polyunsaturated fatty acids that are a component of cell membranes because reaction products (peroxides and hydroperoxides) has also high oxygenating potential. As the result, the process of cell damaging becomes avalanche-like. Damage of macromolecules (and of the whole cell) after ROS acting is named an oxidative stress. It causes aging as well as a broad range of age-related pathological processes (cardiovascular diseases, age-dependent metabolic immunodepression, brain dysfunction, cataract, cancer and so on).

Additions:

The nature provided protection mechanisms from free radicals excess, and most ROS render harmless before they injure any cell structures. The main factors of antioxidant defense of an organism are special enzymes: superoxide dismutase and some other ones. Some antioxidant chemicals are received by the organism with food. Among such antioxidants are vitamin A, vitamin C and vitamin E. Up-to-date pharmacology develops antioxidant supplements which are medicines protecting an organism from free radicals. However, the fact that product of interaction between ROS with macromolecules are permanently found in organs and tissues indicate that systems protecting an organism from free radicals are not enough efficient and that the cells constantly run the danger of oxidative stress.

Criticism:

Whether reducing oxidative damage below normal levels is sufficient to extend lifespan remains an open and controversial question. For example, in roundworms (Caenorhabditis elegans), blocking the production of the naturally occurring antioxidant superoxide dismutase has recently been shown to increase lifespan.

Publications:

  • Harman, Denham. «Free radical theory of aging." Free Radicals: From Basic Science to Medicine. Birkhäuser Basel, 1993. 124–143.
  • Finkel, Toren, and Nikki J. Holbrook. «Oxidants, oxidative stress and the biology of ageing." Nature 408.6809 (2000): 239–247.
  • Dai, Dao-Fu, et al. «Mitochondrial oxidative stress in aging and healthspan." Longev Healthspan 3.6 (2014): 10–1186.
  • Stadtman, Earl R. «Protein oxidation and aging." Free radical research 40.12 (2006): 1250–1258.
  • Berlett, Barbara S., and Earl R. Stadtman. «Protein oxidation in aging, disease, and oxidative stress." Journal of Biological Chemistry 272.33 (1997): 20313–20316.