Effects of dietary restriction and exercise on the age-related pathology of the rat

Abstract

Intervention of the aging process is an effective, experimental means of uncovering the bases of aging. The most efficacious and commonly used intervention used to retard the aging processes is dietary restriction (DR). It increases mean and maximum life spans, delays the appearance, frequency, and severity of many age-related diseases, and more importantly, attenuates much of the physiological decline associated with age. Although the subject of intense research, the mechanism by which DR alters the aging processes is still unknown. Physical exercise is another effective intervention shown to affect aging phenomena, especially when applied in combination with DR. Mild exercise in concert with DR is beneficial, but vigorous exercise coupled with DR could be deleterious. With regard to pathology, exercise generally exerts a salutary influence on age-related diseases, both neoplastic and non-neoplastic, and this effect may contribute to the increase in median life span seen with exercised rats. Exercise coupled with 40% DR was found to suppress the incidence of fatal neoplastic disease compared to the sedentary DR group. Exercise with mild DR suppressed the incidence of multiple fatal disease and chronic nephropathy, and also delayed the occurrence of many age-related lesions compared to the ad libitum (AL) control group. However, these effects may have little bearing on the aging process per se, as maximum life span is only minimally affected. Although not as intensively studied as DR, results from studies that utilize exercise as a research probe, either alone or in combination with DR, have helped to assess the validity of proposed mechanisms for DR and aging itself. Neither the retardation of growth rate nor the increase in physical activity, observed with either exercise or DR, appear to contribute to the anti-aging action of DR. Moreover, results from lifelong exercise studies indicate that the effects of DR do not depend upon changes in energy availability or metabolic rate. The mechanisms involving effects on adiposity or immune function are also inadequate explanations for the action of DR on aging. Of the proposed mechanisms, only one, as postulated by the Oxidative Stress Hypothesis of Aging, tenably accounts for the known effects of DR and exercise on aging.

Effect of Lipid Restriction on Mitochondrial Free Radical Production and Oxidative DNA Damage

“…What are the effects of lipid restriction on longevity? Many studies have discussed whether or not lipids are involved in CR effects, some supporting and some rejecting this idea based on different kinds of endpoint biochemical measurements and experiments 36–39 . But very few studies have directly tested the effect of lipid restriction on longevity.…”

“…Many studies have discussed whether or not lipids are involved in CR effects, some supporting and some rejecting this idea based on different kinds of endpoint biochemical measurements and experiments. [36][37][38][39] But very few studies have directly tested the effect of lipid restriction on longevity. In a long-term study in Fisher 344 rats, increases in maximum and medium life span were found after 40% CR but not after 40% lipid restriction.…”

Update on the oxidative stress theory of aging: Does oxidative stress play a role in aging or healthy aging?

“…For example, most physiological, biochemical and pathological changes with age are delayed or reduced in CR rodents compared to ad libitum fed controls (reviewed in [6]). Age-related development of insulin resistance [142], declines in immune function [143,144], and alterations in neural and behavioral parameters [145,146] are all reduced by CR, and the onset and incidence of age-associated diseases including neoplasia and nephropathies are delayed [147–149], among many other examples. Additionally, the long-lived Ames/Snell dwarf mutations show reduced occurrence or severity of age-related pathologies such as collagen aging [150], osteoarthritis [151], the development of cataracts [152], glomerular nephrosis [152], age-related cognitive decline [153,154], and the slowed progression of multiple forms of spontaneous neoplasia [152,155].…”

Scientific Opinion on the essential composition of total diet replacements for weight control

“…Caloric restriction was shown to reduce the rate of mitochondrial reactive oxygen species production and the rate of oxidative attack to biological macromolecules such as mitochondrial deoxyribonucleic acid (DNA) in rodents (Kim et al, 1996;Ikeno et al, 1997;Masoro, 1998;Lindsay, 1999;Lal et al, 2001;López-Torres et al, 2002). The use of total diet replacements for weight control in obese subjects resulted in a decline in oxidative stress markers, especially in patients with metabolic syndrome (Tzotzas et al, 2008;Tumova et al, 2013).…”