The role of calorie restriction in humans is controversial. Recently, new data in monkeys and humans have provided new insights into the potential role of calorie restriction in longevity.
A study in rhesus monkeys showed a reduction in aging-associated mortality. A number of controlled studies have suggested a variety of beneficial effects during studies of 6-12 months in humans. Major negative effects in humans were loss of muscle mass, muscle strength and loss of bone.
Dietary restriction in rodents has not been shown to be effective when started in older rodents. Weight loss in humans over 60 years of age is associated with increased mortality, hip fracture and increased institutionalization. Calorie restriction in older persons should be considered experimental and potentially dangerous. Exercise at present appears to be a preferable treatment for older persons.
"Moreover, as little as 2.5 h of " nonvigorous " activity per week is associated with 19% reduced risk of mortality (Janssen 2011). Thus, modest low-volume physical activity, in combination with caloric maintenance, may provide an optimal stimulus for preserving , or improving, overall health without the reductions in nutrient intake or body weight that occur with caloric restriction (Morley et al. 2010; Weinheimer et al. 2010). Another advantage is reasonable probability of long-term compliance. "
"When started too early in life, it may cause developmental problems and if started too late, benefits may not be achieved . Furthermore, CR, started late in life could contribute to the anorexia of aging and mortality . Nonetheless the benefits of CR on aging and sarcopenia have lead to the search for CRMs. "
[Show abstract][Hide abstract] ABSTRACT: Sarcopenia refers to age-related loss of muscle mass and function. Several age-related changes occur in skeletal muscle including a decrease in myofiber size and number and a diminished ability of satellite cells to activate and proliferate upon injury leading to impaired muscle remodeling. Although the molecular mechanisms underlying sarcopenia are unknown, it is tempting to hypothesize that interplay between biological and environmental factors cooperate in a positive feedback cycle contributing to the progression of sarcopenia. Indeed many essential biological mechanisms such as apoptosis and autophagy and critical signaling pathways involved in skeletal muscle homeostasis are altered during aging and have been linked to loss of muscle mass. Moreover, the environmental effects of the sedentary lifestyle of older people further promote and contribute the loss of muscle mass. There are currently no widely accepted therapeutic strategies to halt or reverse the progression of sarcopenia. Caloric restriction has been shown to be beneficial as a sarcopenia and aging antagonist. Such results have made the search for caloric restriction mimetics (CRM) a priority. However given the mechanisms of action, some of the currently investigated CRMs may not combat sarcopenia. Thus, sarcopenia may represent a unique phenotypic feature of aging that requires specific and individually tailored therapeutic strategies.
"One of the interventions most reliably associated with an extension of lifespan and a reduced rate of aging is calorie restriction (CR 1 ), the reduction of food intake without malnutrition. CR has been shown to extend the lifespan of yeast, fl ies, worms, fi sh, rodents, and rhesus monkeys (Fontana et al. 2010) and, in mammals, decrease the risk of age-related diseases such as diabetes, cardiovascular diseases, and cancers (Fontana and Klein 2007; Morley et al. 2010). Mouse models have been used extensively to investigate the underlying mechanisms of the antiaging effects of CR. "
[Show abstract][Hide abstract] ABSTRACT: Mice are an ideal mammalian model for studying the genetics of aging: considerable resources are available, the generation time is short, and the environment can be easily controlled, an important consideration when performing mapping studies to identify genes that influence lifespan and age-related diseases. In this review we highlight some salient contributions of the mouse in aging research: lifespan intervention studies in the Interventions Testing Program of the National Institute on Aging; identification of the genetic underpinnings of the effects of calorie restriction on lifespan; the Aging Phenome Project at the Jackson Laboratory, which has submitted multiple large, freely available phenotyping datasets to the Mouse Phenome Database; insights from spontaneous and engineered mouse mutants; and complex traits analyses identifying quantitative trait loci that affect lifespan. We also show that genomewide association peaks for lifespan in humans and lifespan quantitative loci for mice map to homologous locations in the genome. Thus, the vast bioinformatic and genetic resources of the mouse can be used to screen candidate genes identified in both mouse and human mapping studies, followed by functional testing, often not possible in humans, to determine their influence on aging.
ILAR journal / National Research Council, Institute of Laboratory Animal Resources 02/2011; 52(1):4-15. DOI:10.1093/ilar.52.1.4 · 2.39 Impact Factor
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