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The Effects of Calorie Restriction on Aging: a Brief Review

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The Effects of Calorie Restriction on Aging: a Brief Review Eur opean Rev iew for Med ical and Pharmacol ogical Sci ences 2016; 20: 2468-2473 The effects of calorie restriction on aging: a brief review K.A. AL-REGAIEY Department of Physiology, Aging Research Chair, College of Medicine, King Saud University, Riyadh, Saudi Arabia Abstract. – Calorie restriction (CR) without the occurrence of chronic nephropathies and car - malnutrition slows aging and increase average diomyopathies and diabetes, autoimmune and and maximal lifespan in model organisms and respiratory diseases 5. In nonhuman primates , two rodents. In human and non-human primates, independent studies have shown mixed results. CR has beneficial effects on human longevity One 6 carried out in two age groups young (1-14 and reduces the incidence of age-related dis - eases such as obesity, diabetes mellitus hyper - years old) and old (16-23 years old) of rhesus tension, cardiovascular disease and cancer. CR monkeys at National Institute on Aging (NIA) in exerts its anti-aging effects through different Bethesda, Maryland, found no difference in the mechanisms including small noncoding RNA longevity of treated versus untreated animals fol - molecules (sncRNAs), the composition of diet lowing 30% calorie restriction . Another study 7 at and IGF-1 signaling. The aim of this review was the Wisconsin National Primate Research Centre to discuss recent developments to understand (WNPRC) from the University of Wisconsin, the consequences and mechanisms of CR on longevity. Madison, had found a positive effect of CR on longevity, reporting 13% mortality for the CR Key Words: group compared to 37% in the control group, al - Aging, Dietary restriction, Small non-coding RNAs. though not statistically significant. A detailed analysis of these two studies highlighted the dif - ference in the genetic background, the age of on - set and diet composition. However, these two re - Introduction ports suggest a beneficial effect of CR on health span in nonhuman primates which can serve as a Calorie restriction (CR) defined as a reduction good aging model to understand different in calorie intake below usual ad libitum without longevity factors that can be translated to human malnutrition, slows aging, extend maximal and aging and human health. average life span in animals of diverse origin 1,2 . Although a wealth of data is available in mice The role of CR to enhance life span dates back to and primates, the beneficial effects CR in hu - early 20 th century when Osborne et al 3 reported mans has been observed in many settings. Data that female rats having retarded growth and de - from natural and controlled investigations sug - layed sexual maturity lived longer than those that gest that CR with adequate nutrition has useful grew rapidly . McCay et al 4 published the first sci - effects on human longevity and protects against entific paper to report that restricting food intake the development of obesity, cardiovascular dis - at or soon after weaning in rats, extended median ease, hypertension and cancer. Individuals from and maximum life span and decreased the onset Okinawa, Japan, who usually have low calorie and severity of chronic diseases. Subsequently, intake compared to the residents of the main 30-60% reduction in calorie intake below usual Japanese Island, had very low mortality from ad libitum had increased the average and maxi - coronary heart disease and cancer 8. A controlled mal life span in many species of mouse and rat study 9, Biosphere 2 (carried out in normal weight strains 2. As cancer accounts for major cause for individuals) reported that CR with high levels of mortality in rodents (70-80%), CR has been physical activity, reduced insulin levels, blood shown to inhibit the development of different pressure, body weight, cholesterol and other types of tumors in mice and delayed or prevented physiological and anthropometric parameters. 2468 Corresponding Author: Khalid A Al-Regaiey, Ph.D; e-mail: [email protected] The effects of calorie restriction on aging: a brief review Data obtained from Calorie Restriction Society muscle mass and positive nitrogen balance. Thus, (CRS) members, taking 30% fewer calories than restricting certain amino acids, not complete diet age- and sex-matched controls, exhibited positive has beneficial effects on longevity. effects of CR on various physiologic and meta - Many cellular, metabolic and physiological bolic parameters such as a decrease in BMI, total mechanisms have been implicated for life ex - body fat, serum cholesterol, triglycerides, fasting tending and anti-aging effects of CR 10 . Evolu - glucose and insulin levels 10 . CRS members also tionary conserved nutrient - and energy - sensing had lower levels of blood pressure and inflamma - pathways which include, IGF-1/insulin signaling, tory markers (C-reactive proteins, tumor necrosis mTOR, sirtuins, AMPK and GCN2 have been 16 factor α and interleukin-6) than age- and sex- suggested in the regulation of aging by CR . In matched healthy controls . No adverse effects of mice, mutations that suppress insulin/IGF- CR such as eating disorder, cognitive impair - 1/mTOR pathways increase health and life ment, depressed mood or change in spontaneous span 17 . Ames dwarf mice ( df/df ) deficient in physical activity has been observed in humans growth hormone (GH), prolactin and thyroid practicing CR, making it a useful intervention 11 . stimulating hormone (TSH), had significantly Experimental evidence suggested that CR im - longer life span than their normal siblings 18 . Oth - proved memory in elderly 12 . er mutant mice, deficient in GH/GH receptor or The composition of diet is important while GH resistant, lived longer (median and maximal considering the role of CR on longevity. Restric - life span), exhibited delayed symptoms of aging tion of macronutrients such as proteins, carbohy - and had reduced circulating IGF-1 levels 19 . These drates or fats has beneficial effects. Limiting the mutant mice had reduced mTOR signaling, re - consumption of certain amino acids such as me - sulting in reduced cell size and protein synthesis thionine and tryptophan extend longevity and which possibly contributed to delayed aging and prevent multiple age-related diseases. In mice, extended longevity 20 . methionine restriction (MR) had reduced levels Increased resistance to oxidative stress is an - of serum IGF-1, insulin, glucose and thyroid hor - other possible mechanism for longevity and CR. mone and visceral fat deposition 13 . An analysis of In Ames dwarf mice, protection form oxidative diet regimen of Okinawa inhabitants indicates the damage has been associated with reduced pro - presence of plant-based low protein diets consist duction of reactive oxygen species (ROS) and in - mostly of vegetables, fruits and grains 14 . A recent creased activity of anti-oxidant enzymes 18 . How - cross-sectional study 15 based on US NHANES III ever, accumulating data does not support a major database which includes dietary intake data, re - role of oxidative stress in modulating aging in ported an association of age with protein con - mammals 21 . Mutant mice deficient in several an - sumption and mortality. A comparative analysis tioxidant enzymes or overexpressing the major of individuals from two age groups 50-65 and ≥ antioxidant enzymes (CuZnSOD, Mn superoxide 65 years of age revealed that younger population dismutase, and catalase) did not have extended having consumption of > 20% of calories from life span or decreased age-related diseases 22,23 . proteins had a 4-fould increase in risk of devel - Hence, whether the reduction in oxidative dam - oping cancer and a 75% increase in mortality age by CR has any role in life extension is still an compared to subjects taking <10% of calories open question. from proteins. However, when the protein source Summing up, accumulated evidence indicates was plant-based, this association was eliminated that moderate CR associated with adequate nutri - and there was a decrease in cancer mortality. On tion protects against many age-related anomalies the other hand, older population on high protein in many species including humans . However, intake had reduced cancer and overall mortality. much work is needed to understand the cellular These findings suggest that reduced protein in - and molecular mechanisms responsible for bene - take during middle age and moderate to high pro - ficial effects of CR. tein consumption in older individuals may help in longevity and healthy life span 15 . Variations in Small Noncoding RNAs, Calorie the protein consumption reflect the requirements Restriction and Aging of different age groups, if high protein consump - Small noncoding RNAs (sncRNAs) are a com - tion has negative effects in younger individuals, plex category of RNA molecules, less than 400 it is equally essential in older individuals for pro - nucleotides in length, which are not translated in - viding essential amino acids to maintain healthy to proteins but they control a variety of cellular 2469 K.A. Al-Regaiey functions and biological processes by interacting lation among miRNA, aging and CR. Mercken et with target genes 24 . The sncRNAs circulate in the al 34 have reported differential miRNA expression bloodstream and extracellular spaces and can in the skeletal muscle of young and aged rhesus modify gene expression of target cells and are al - monkeys and CR had reversed these alterations. so part of cell-to-cell communication and signal - In mice, CR had prevented the elevation of age- ing system involved in disease
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