The Free Radical Theory of Aging: A Critique and Unresolved Questions

Carlson, John C.; Forbes, W. F.

doi:10.1017/s071498080001148x

Cited by 5 publications

(2 citation statements)

References 20 publications

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“…As proposed by Harman (1981), aging is due to the progressive increase in cellular damage caused by free radical reactions in the organism. This notion is supported by numerous studies (Pryor, 1987;Carlson and Forbes, 1992;Orr and Sohal, 1994). For example, we measured progressive increases in the superoxide radical and LP in the brain, heart and liver of aging rats.…”

Section: Discussionsupporting

confidence: 63%

Oxidative stress in hypopituitary dwarf mice and in transgenic mice overexpressing human and bovine GH

Carlson

Bharadwaj

Bartke

1999

AGE

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Growth hormone (GH) stimulates metabolic activity. The purpose of this study was to examine whether it is involved in the aging process by increasing oxidative stress. Inorganic peroxides and lipid peroxides were measured in kidney and liver samples in dwarf mice that are deficient in GH, prolactin and thyrotropin and in transgenic mice that produce high levels of GH. In normal male mice, there was an increase in inorganic peroxides in the kidney with age. Levels were lower in old male dwarfs when compared with normal male mice of similar age. Unexpectedly, concentrations of inorganic peroxides were frequently lower in transgenic male and female mice expressing extra copies of GH than in normal controls. Lipid peroxide concentrations were more variable. Transgenic animals expressing bovine GH had the highest levels of lipid peroxides. In dwarfs, kidney levels were similar to those of normal mice but concentrations in the liver were more variable. This study does not indicate that the decrease in life span in transgenic mice producing high levels of GH is due to an increase of oxidative stress. Rather, it suggests that expression of extra copies of the GH gene may lead to a compensatory increase in antioxidant protection.

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Section: Discussionsupporting

confidence: 63%

Oxidative stress in hypopituitary dwarf mice and in transgenic mice overexpressing human and bovine GH

Carlson

Bharadwaj

Bartke

1999

AGE

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“…One of the difficult and unresolved questions regarding the free radical theory concerns initiation of the process (Carlson & Forbes, 1992). Oxygen radicals are produced all the time, but the effects of aging become apparent sometime after maturation.…”

Section: Cellular Sourcementioning

confidence: 99%

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

Carlson¹,

Sawada²

1996

Can. J. Aging

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RÉSUMÉSelon 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.

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