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The Free Radical Theory of Aging and a Look at Changes in the Hypothalamus

Published online by Cambridge University Press:  29 November 2010

J. C. Carlson  and
M. Sawada
J. C. Carlson
Affiliation:
University of Waterloo
M. Sawada
Affiliation:
University of Waterloo
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Abstract

According to the free radical theory, aging is caused by the damaging effects of oxygen radicals. These agents are produced continuously and they become toxic when their intra-cellular levels become elevated. Although well-known for the damage they cause, recent studies indicate that free radicals may also have a beneficial side regulating some of the processes within a cell. With aging, however, it seems that the ability to control endogenous concentrations declines, and rising levels become progressively more harmful. In addition to the primary changes, the effects of free radical damage should also be examined at the secondary level. Because of its importance in regulating homeostatic mechanisms, it is possible that in this regard the hypothalamus may play a crucial role in the aging process. Progressive loss of function in this centre may lead to systemic changes which cause widespread disruption throughout the organism.

Résumé

Selon la théorie du radical libre, le vieillissement est produit par l'effet endommageant des radicaux d'oxygène. Ces radicaux sont produits de façon constante et deviennent toxiques quand le niveau de la concentration intracellulaire devient élevé. Malgré cet effet d'infamie, des études récentes indiquent qu'ils peuvent avoir un côté bénéfique en régulant certains mécanismes dans une cellule. Mais, avec le vieillissement, il semble que la capacité de réguler la concentration intracellulaire s'abaisse, et l'élévation du niveau devient toxique avec le temps. Il faut aussi examiner les effets endommageant des radicaux libres sur un niveau supérieur. À cause de la prééminence de l'hypothalamus comme centre régulateur homéostatique, il est possible que l'hypothalamus puisse jouer un rôle critique dans le processus de vieillissement. La perte progressive des fonctions dans ce centre peut mener à des changements systémiques qui peuvent provoquer des perturbations dans tout l'organisme.

Keywords

Free RadicalsAgingOxidative StressIntegrationHypothalamus.Radicaux libresvieillissementstress oxidatifintégrationhypothalamus.
Type
Articles
Information
Canadian Journal on Aging / La Revue canadienne du vieillissement , Volume 15 , Issue 1 , Spring/printemps 1996 , pp. 44 - 53
Copyright
Copyright © Canadian Association on Gerontology 1996

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References

Beauchamp, C., & Fridovich, I. (1970). A mechanism for the production of ethylene from methional. Journal of Biological Chemistry, 245, 4641–4646.Google Scholar
Carlson, J.C., & Forbes, W.F. (1992). The free radical theory of aging: A critique and unresolved questions. Canadian Journal on Aging, 11, 262–268.Google Scholar
Chance, B., Sies, H., & Boveris, A. (1979). Hydrogen peroxide metabolism in mammalian organs. Physiological Review, 59, 527–605.CrossRefGoogle ScholarPubMed
Chaudhary, A.K., Nokubo, M., Reddy, G.R., Yeola, S.N., Morrow, J.D., Blair, I.A., & Mannott, L.J. (1994). Detection of endogenous malondialdehyde-deoxyguanosine adducts in human liver. Science, 265, 1580–1582.CrossRefGoogle ScholarPubMed
Chen, J.J., & Yu, B.P. (1994). Alterations in mitochondrial membrane fluidity by lipid peroxidation products. Free Radical Biology and Medicine, 17, 411–418.Google Scholar
Clark, R.A., Leidal, K.G., Pearson, D.W., & Nauseef, W.M. (1987). NADPH oxidase of human neutrophils. Journal of Biological Chemistry, 262, 4065–4074.Google Scholar
Cutler, R.G. (1992). Genetic stability and oxidative stress: Common mechanisms in aging and cancer. In Emerit, I. & Chance, B. (Eds.), Free Radicals and Aging (pp. 31–46). Basel: Birkhauser Verlag.CrossRefGoogle Scholar
Enesco, H.E. (1993). Rotifers in aging research: Use of rotifers to test various theories of aging. Hydrobiologia, 255/256, 59–70.Google Scholar
Freeman, B.A., & Crapo, J.D. (1982). Biology of Disease: Free radicals and tissue injury. Laboratory Investigation, 47, 412–426.Google ScholarPubMed
Goldstein, S. (1990). Replicative senescence: The human fibroblast comes of age. Science, 249, 1129–1133.CrossRefGoogle ScholarPubMed
Halliwell, B., & Gutteridge, J.M.C. (1989). Free Radicals in Biology and Medicine (2nd ed.). Oxford: Clarendon Press.Google Scholar
Harman, D. (1956). Aging: A theory based on free radical and radiation chemistry. Journal of Gerontology, 11, 298–300.CrossRefGoogle ScholarPubMed
Harman, D. (1981). The aging process. Proceedings of the National Academy of Sciences (USA), 78, 7124–7128.CrossRefGoogle ScholarPubMed
Landfield, P.W. (1994). The role of glucocorticoids in brain aging and Alzheimer's disease: An integrative physiological hypothesis. Experimental Gerontology, 29, 3–11.Google Scholar
Meites, J., Goya, R., & Takahashi, S. (1987). Why the neuroendocrine system is important in aging processes. Experimental Gerontology, 22, 1–15.CrossRefGoogle ScholarPubMed
Miura, M., Zhu, H., Rotello, R., Hartweig, E., & Yuan, J. (1993). Induction of apoptosis in fibroblasts by IL-1 Beta-converting enzyme, a mammalian homologue of the C. elegans cell death gene ced-3. Cell, 75, 653–659.Google Scholar
Nauseef, W.M., Volpp, B.D., McCormick, S., Leidal, K.G., & Clark, R.A. (1991). Assembly of the neutrophil respiratory burst oxidase. Journal of Biological Chemistry, 266, 5911–5917.Google Scholar
Nohl, H., & Hegner, D. (1978). Do mitochondria produce oxygen radicals in vivo? European Journal of Biochemistry, 82, 563–567,CrossRefGoogle ScholarPubMed
Orr, W.C., & Sohal, R.S. (1994). Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science, 263, 1128–1130.Google Scholar
Phillips, J.P., Campbell, S.D., Michaud, D., Charbonneau, M., & Hilliker, A.J. (1989). Null mutation of copper/zinc superoxide dismutase in Drosophila confers hypersensitivity to paraquat and reduced longevity. Proceedings of the National Academy of Science (U.S.A.), 86, 2761–2765.Google Scholar
Riley, J.C.M., & Carlson, J.C. (1988). Impairment of gonadotropin binding occurs during membrane rigidification in plasma membrane samples prepared from regressed rat corpora lutea. Canadian Journal of Physiology and Pharmacology, 66, 76–79.CrossRefGoogle ScholarPubMed
Robertson, O.H. (1961). Prolongation of the life span of Kokanee Salmon (Oncor-hunchus nerka kennerlyi) by castration before beginning of gonad development. Proceedings of the National Academy of Science (U.S.A.), 47, 609–621.CrossRefGoogle ScholarPubMed
Rosen, D.R., et al. (1993). Mutations in Cu/Zn Superoxide dismutase gene are associated with familial amyotrophic laterol sclerosis. Nature, 362, 59–62.CrossRefGoogle ScholarPubMed
Sarkar, D.K., Gottschall, P.E., & Meites, J. (1982). Damage to hypothalamic dopaminergic neurons is associated with development of prolactin-secreting pituitary tumours. Science, 218, 684–686.CrossRefGoogle Scholar
Sawada, M., & Carlson, J.C. (1987). Changes in Superoxide radical and lipid peroxide formation in the brain, heart and liver during the lifetime of the rat. Mechanisms of Ageing and Development, 41, 125–137.Google Scholar
Sawada, M., & Carlson, J.C. (1989). Superoxide radical production in plasma membrane samples from regressing rat corpora lutea. Canadian Journal of Physiology and Pharmacology, 67, 465–471.CrossRefGoogle ScholarPubMed
Sawada, M., & Carlson, J.C. (1990). Biochemical changes associated with the mechanism controlling superoxide radical formation in the aging rotifer. Journal of Cellular Biochemistry, 44, 153–165.Google Scholar
Sawada, M., & Carlson, J.C. (1991). Rapid plasma membrane changes in superoxide radical formation, fluidity, and phospholipase A2 activity in the corpus luteum of the rat during induction of luteolysis. Endocrinology, 128, 2992–2998.Google Scholar
Sawada, M., & Carlson, J.C. (1994). Studies on the mechanism controlling generation of superoxide radical in the rat corpus luteum during regression. Endocrinology, 135, 1645–1650.CrossRefGoogle ScholarPubMed
Sawada, M., Sester, U., & Carlson, J.C. (1992). Superoxide radical formation and associated biochemical alterations in the plasma membrane of brain, heart and liver during the lifetime of the rat. Journal of Cellular Biochemistry, 48, 296–304.CrossRefGoogle ScholarPubMed
Sawada, M., Sester, U., & Carlson, J.C. (1993). Changes in superoxide radical formation, lipid peroxidation, membrane fluidity and proteolytic activity in aging and spawning Chinook salmon. Mechanisms of Ageing and Development, 69, 137–148.Google Scholar
Schnabel, J. (1993). New Alzheimer's therapy suggested. Science, 260, 1719–1720.Google Scholar
Semsei, I., Rao, G., & Richardson, A. (1991). Expression of superoxide dismutase and catalase in rat brain as a function of age. Mechanism of Ageing and Development, 58, 13–19.Google Scholar
Sestini, E.A., Carlson, J.C., & Allsopp, R. (1991). The effects of ambient temperature on life span, lipid peroxidation, superoxide dismutase, and phospholipase A2 activity in Drosophila melanogaster. Experimental Gerontology, 26, 385–395.CrossRefGoogle ScholarPubMed
Shi, L., Sawada, M., Sester, U., & Carlson, J.C. (1994). Alterations in free radical activity in aging drosophila. Experimental Gerontology, 29, 575–584.CrossRefGoogle ScholarPubMed
Shock, N. (1977). Systems integration. In Finch, C.E. & Hayflick, L. (Eds.), Handbook of biology of Aging (pp. 639–665). New York: Van Nostrand Reinhold.Google Scholar
Shreck, R., & Baeuerle, P.A. (1991). A role for oxygen radicals as second messengers. Trends in Cell Biology, 1, 39–42.CrossRefGoogle Scholar
Slotboom, A.J., Verheij, H.M., & De Haas, G.H. (1982). On the mechanism of phospholipase A2. In Hawthorne, J.N. & Ansell, G.B. (Eds.), Phospholipids (V. 4) (pp. 359–371). Amsterdam: Elsevier Biomedical Press.Google Scholar
Sohal, R.S., & Allen, R.G. (1990). Oxidative stress as a causal factor in differentiation and aging: A unifying hypothesis. Experimental Gerontology, 25, 499–522.CrossRefGoogle ScholarPubMed
Sohal, R.S., Svensson, I., Sohal, B.H., & Brunk, U.T. (1989). Superoxide anion radical production in different species. Mechanisms of Aging and Development, 49, 129–135.Google Scholar
Sonntag, W.E., Steger, R.W., Forman, L.J., & Meites (1980). Decreased pulsatile release of growth hormone in old male rats. Endocrinology, 107, 1875–1879.Google Scholar