Low-calorie diet and aging
Review of research articles published in 2009 that have made or will make a significant contribution to the study of aging – Part 4.
Providing a balanced intake of nutrients, a low-calorie diet (ND) delays aging and increases the life expectancy of various species, but its effect on the primate body has not been fully studied. In 2009, the results of a 20-year study of the effects of a low-calorie diet, the observance of which was started in adulthood, on rhesus monkeys demonstrated that moderate ND reduced the frequency of age-related deaths. At the time under consideration, 50% of the monkeys of the control group and 80% of the animals kept on the ND remained alive. ND delayed the onset of a number of age-related pathologies, such as diabetes, cancer, diseases of the cardiovascular system and brain atrophy [24]. The results of studying the effects of ND on primates gave experts hope that ND can have similar effects on humans.
In 2009, numerous studies continued to identify the relationship between signaling mechanisms associated with a low-calorie diet and longevity, including mechanisms mediated by Sir2 and p53 proteins in the body of fruit flies [25] and E3-ubiquitin ligase in the body of C.elegans worms [26], as well as components of various levels of the mechanism mediated by the TOR protein (rapamycin target): RHEB-1 in C.elegans [27], Tor1 and Sch9 (homologue of mammalian Akt and S6K kinases) in yeast [28] and 4E-BP (protein binding eukaryotic translation initiation factor 4E) drosophila flies [29]. It has been demonstrated that glucose shortens the lifespan of C.elegans worms by suppressing the activity of the DAF-16/FOXO complex and the expression of the aquaporin gene [30]. In addition, the involvement of the HIF-mediated mechanism (hypoxia-induced factor) in the parameters of aging and life expectancy of C.elegans was revealed [31, 32]. The differing results of the two studies as a whole managed to lead to a common denominator [33]. Also in 2009, it was shown that in C.elegans, the effects of a low-calorie diet are mediated by a system of independent but overlapping mechanisms [34], which indicates the existence of a so-called "ND system". It is also noteworthy that SIRT1 synthesized by neurons regulates endocrine and behavioral reactions caused by a low-calorie diet [35].
It has also been demonstrated that when the functioning of the growth hormone receptor is impaired, a low-calorie diet does not have a positive effect on the effect of insulin and longevity [36]. In normal mice, ND increased the sensitivity of liver and muscle cells to insulin. Innate insulin sensitivity, characteristic of GHRKO mice, may be due to a decrease in the activity of inhibitory phosphorylation of serine, which is part of IRS-1 (substrate 1 of the insulin receptor), in the muscles. Compared with normal animals, ND did not cause an additional increase in insulin activity (insulin sensitivity) in the body of GHRKO mice, which may explain the absence of the influence of ND on the life expectancy of these long-lived animals [36].
And, finally, the assumption was tested, according to which the redistribution of nutrients from the reproduction processes to the maintenance of the functioning of somatic cells can explain the life-extending effect of ND. In this case, low fertility and long life in conditions of calorie restriction and high fertility in conditions of food abundance would be mutually exclusive concepts. The additional introduction of methionine into the diet with a limited caloric content proved to be a necessary and sufficient condition for increasing fertility to levels provided by food abundance, but was not accompanied by a decrease in life expectancy. Thus, the redistribution of nutrients does not explain the body's reaction to a low-calorie diet. On the contrary, a decrease in the activity of the signaling mechanism mediated by insulin/insulin-like growth factor prevented a shortening of life expectancy in conditions of adequate nutrition [37].
Continuation: Pharmacological interventions in the aging process.
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