Free radical theory of aging

doi:10.1016/0921-8734(92)90030-S

Mutation Research/DNAging

Volume 275, Issues 3–6, September 1992, Pages 257-266

https://doi.org/10.1016/0921-8734(92)90030-S Get rights and content

Abstract

Free radical reactions are ubiquitous in living things. Studies on the origin and evolution of life provide a reasonable explanation for the prominent presence of this unruly class of chemical reactions. These reactions have been implicated in aging. This phenomenon is the accumulation of changes responsible for the sequential alterations that accompany advancing age and the associated progressive increases in the chance of disease and death. Aging changes are attributed to the environment and disease, and to an inborn process, the aging process. The latter produces aging changes at an exponentially increasing rate with advancing age. Past improvements in general living conditions have decreased the chances for death so that they are now near limiting values in the developed countries. In these countries the intrinsic aging process in the major cause of disease and death after about age 28. The free radical theory of aging postulates that aging changes are caused by free radical reactions. The data supporting this theory indicate that average life expectancy at birth may be increased by 5 or more years, by nutritious low caloric diets supplemented with one or more free radical reaction inhibitors.

References (115)

G. Block
Dietary guidelines and the results of food consumption surveys
Am. J. Clin. Nutr.
(1991)
E. Byrne et al.
Mitochondrial theory of senescence: respiratory chain protein studies in human skeletal muscle
Mech. Ageing Dev.
(1991)
I. Ceballos-Picot et al.
Neuronal-specific expression of human copper-zinc superoxide dismutase gene in transgenic mice: animal model of gene dosage effects in Down's syndrome
Brain Res.
(1991)
Y.J.D. Chiu et al.
Effect of age on the function of mitochondria isolated from brain and heart tissue
Exp. Gerontol.
(1980)
R.C. Cutler
Antioxidants, aging and longevity
R.G. Cutler
Antioxidants and aging
Am. J. Clin. Nutr.
(1991)
M.L. Heidrick et al.
Effect of dietary 2-mercaptoethanol on the life span, immune system, tumor incidence and lipid peroxidation damage in spleen lymphocytes of aging BC3F₁ mice
Mech. Ageing Dev.
(1984)
A.M. Hruszkewycz
Evidence for mitochondrial DNA damage by lipid peroxidation
Biochem. Biophys. Res. Commun.
(1988)
M. Lemoyne et al.
Breath pentane analysis as an index of lipid peroxidation: a functional test of vitamin E status
Am. J. Clin. Nutr.
(1987)
T. Ljones et al.
Evidence for one-electron transfer by the Fe proteins of nitrogenase
Biochem. Biophys. Res. Commun.
(1978)

P.A. Loach et al.

Biol. Rev.

(1990)

J. Miquel et al.

Mitochondrial role in cell aging

Exp. Gerontol.

(1980)

J. Miquel et al.

Experimental support for the mitochondrial mutation theory of cell aging

Age

(1982)

K.D. Munkres

Pharmacogenetics of cyclic guanylate, antioxidants, and antioxidant enzymes in Neurospora

Free Radical Biol. Med.

(1990)

National Center for Health Statistics

Annual Summary of Births, Marriages, Divorces, and Deaths: United States 1988

I. Reveillaud et al.

Expression of bovine superoxide dismutase in Drosophila melanogaster augments resistance to oxidative stress

Mol. Cell. Biol.

(1991)

E.L. Schneider

Theories of aging: a perspective

R.S. Sohal et al.

Effect of age on superoxide dismutase, catalase, glutathione reductase, inorganic peroxides, TBA-reactive material, GSH/GSSG, NADPH/NADP⁺ in Drosophila melanogaster

Mech. Ageing Dev.

(1990)

R.S. Sohal et al.

Age-related changes in antioxidant enzymes and peroxidant generation in tissues of the rat with special reference to parameters in two insect species

Free Radical Biol. Med.

(1990)

R.S. Sohal et al.

Hydrogen peroxide release by mitochondria increases during aging

Mech. Ageing Dev.

(1991)

R. Adelman et al.

Oxidative damage to DNA: Relation to species metabolic rate and life span

K.I. Altman et al.

Radiation Chemistry

B.N. Ames et al.

Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused ageing and cancer: a hypothesis

B.N. Ames et al.

Chemical carcinogenesis: too many rodent carcinogens

B.N. Ames et al.

Dietary pesticides (99.99% all natural)

B.N. Ames et al.

Nature's chemicals and synthetic chemicals: comparative toxicology

J.W. Baynes

Role of oxidative stress in development of complications in diabetes

Diabetes

(1991)

J. Bjorksten

The cross linkage theory of aging

J. Am. Geriat. Soc.

(1968)

A.D. Blackett et al.

Tissue vitamin E levels and lipofuscin accumulation with age in the mouse

J. Gerontol.

(1981)

B. Brian et al.

Mitochondrial mutations may increase oxidative stress: implications for carcinogenesis and aging

Free Radical Biol. Med.

(1990)

N.P. Bun-Hoi et al.

Age retardation in the rat by nordihydroguaiaretic acid

C.R. Seances Soc. Biol.

(1959)

G.W. Casarett

Similarities and contrasts between radiation and time pathology

B. Chance et al.

Hydroperoxide metabolism in mammalian organs

Physiol. Rev.

(1979)

N.K. Clapp et al.

Effects of the antioxidant butylated hydroxytoluene (BHT) on mortality in BALB/c mice

J. Gerontol.

(1979)

A. Comfort

Effect of ethoxyquin on the longevity of C3H mice

Nature

(1971)

R.C. Cutler

Peroxide-producing potential of tissues: inverse correlation with longevity of mammalian species

A.T. Diplock

Antioxidant nutrients and disease prevention: an overview

Am. J. Clin. Nutr.

(1991)

L.I. Dublin et al.

The contribution of medical and sanitary science to health and longevity

J.A. Dunn et al.

Age-dependent accumulation of N^ϵ-(carboxymethyl)lysine and N^ϵ-(carboxymethyl)hydroxylysine in human skin collagen

Biochemistry

(1991)

N.M. Emanuel

Free radicals and the action of inhibitors of radical processes under pathological states and aging in living organisms and man

Q. Rev. Biophys.

(1976)

N.M. Emanuel et al.

Drug for prophylaxis of aging and prolongation of lifetime

Chem. Abst.

(1981)

C.J. Epstein et al.

Transgenic mice with increased Cu/Zn-superoxide dismutase activity: animal model of dosage effects in Down's syndrome

J.E. Fleming et al.

Is cell aging caused by respiratory-dependent injury to the mitochondrial genome?

Gerontology

(1982)

L. Flohe et al.

Glutathione peroxidases

B.A. Freeman et al.

Biology of disease: free radicals and tissue injury

Lab. Invest.

(1982)

B.A. Freeman

Biological sites and mechanisms of free radical production

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Free radical theory of aging

Abstract

Am. J. Clin. Nutr.

Mech. Ageing Dev.

Brain Res.

Exp. Gerontol.

Am. J. Clin. Nutr.

Mech. Ageing Dev.

Biochem. Biophys. Res. Commun.

Am. J. Clin. Nutr.

Biochem. Biophys. Res. Commun.

Biol. Rev.

Exp. Gerontol.

Age

Free Radical Biol. Med.

Mol. Cell. Biol.

Mech. Ageing Dev.

Free Radical Biol. Med.

Mech. Ageing Dev.

Oxidative damage to DNA: Relation to species metabolic rate and life span

Radiation Chemistry

Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused ageing and cancer: a hypothesis

Chemical carcinogenesis: too many rodent carcinogens

Dietary pesticides (99.99% all natural)

Nature's chemicals and synthetic chemicals: comparative toxicology

Role of oxidative stress in development of complications in diabetes

Diabetes

The cross linkage theory of aging

J. Am. Geriat. Soc.

Tissue vitamin E levels and lipofuscin accumulation with age in the mouse

J. Gerontol.

Mitochondrial mutations may increase oxidative stress: implications for carcinogenesis and aging

Free Radical Biol. Med.

Age retardation in the rat by nordihydroguaiaretic acid

C.R. Seances Soc. Biol.

Similarities and contrasts between radiation and time pathology

Hydroperoxide metabolism in mammalian organs

Physiol. Rev.

Effects of the antioxidant butylated hydroxytoluene (BHT) on mortality in BALB/c mice

J. Gerontol.

Effect of ethoxyquin on the longevity of C3H mice

Nature

Peroxide-producing potential of tissues: inverse correlation with longevity of mammalian species

Antioxidant nutrients and disease prevention: an overview

Am. J. Clin. Nutr.

The contribution of medical and sanitary science to health and longevity

Age-dependent accumulation of Nϵ-(carboxymethyl)lysine and Nϵ-(carboxymethyl)hydroxylysine in human skin collagen

Biochemistry

Free radicals and the action of inhibitors of radical processes under pathological states and aging in living organisms and man

Q. Rev. Biophys.

Drug for prophylaxis of aging and prolongation of lifetime

Chem. Abst.

Transgenic mice with increased Cu/Zn-superoxide dismutase activity: animal model of dosage effects in Down's syndrome

Is cell aging caused by respiratory-dependent injury to the mitochondrial genome?

Gerontology

Glutathione peroxidases

Biology of disease: free radicals and tissue injury

Lab. Invest.

Biological sites and mechanisms of free radical production

Age-dependent accumulation of N^ϵ-(carboxymethyl)lysine and N^ϵ-(carboxymethyl)hydroxylysine in human skin collagen