Calorie restriction is known to increase lifespan in many but not all species and may perhaps not do so in humans. Exceptions to life extension have been identified in the laboratory and others are known in nature. Given the variety of physiological responses to variation in food supply that are possible, evolutionary life history theory indicates that an increased investment in maintenance in response to resource shortage will not always be the strategy that maximises Darwinian fitness.
Caloric restriction (CR) is the only experimental nongenetic paradigm known to increase lifespan. It has broad applicability and extends the life of most species through a retardation of aging. There is considerable interest in the use of CR in humans, and animal studies can potentially tell us about the impacts. In this article we highlight some of the things that animal studies can tell us about CR in humans. Rodent studies indicate that the benefits of CR on lifespan extension are related to the extent of restriction.
BACKGROUND: We review studies showing that CR acts rapidly, even in late adulthood, to extend health- and lifespan in mice. These rapid physiological effects are closely linked to patterns of gene expression in liver and heart. Non-human primate and human studies suggest that the signal transduction pathways responsible for the lifespan and health effects of caloric restriction (CR) may also be involved in human longevity. Thus, pharmaceuticals capable of mimicking the effects of CR (and other methods of lifespan extension) may have application to human health.
The mechanisms that determine the lifespan of an organism are still largely a mystery. One goal of ageing research is to find drugs that would increase lifespan and vitality when given to an adult animal. To this end, we tested 88,000 chemicals for the ability to extend the lifespan of adult Caenorhabditis elegans nematodes. Here we report that a drug used as an antidepressant in humans increases C. elegans lifespan. In humans, this drug blocks neural signalling by the neurotransmitter serotonin. In C.
The focus of this review is on current research involving long-term calorie restriction (CR) and the resulting changes observed in physiological and behavioral outcomes in humans. Special emphasis will be given to the first completed clinical studies which are currently investigating the effects of controlled, high-quality energy-restricted diets on both biomarkers of longevity and on the development of chronic diseases related to age in humans.
Trans-resveratrol or (E)-resveratrol [3,4',5 trihydroxy-trans-stilbene, t-RESV or (E)-RESV] is a natural component of Vitis vinifera L. (Vitaceae), abundant in the skin of grapes (but not in the flesh) and in the leaf epidermis and present in wines (especially red wines). In in vitro, ex vivo and in vivo experiments, t-RESV exhibits a number of biological activities, including anti inflammatory, antioxidant, platelet antiaggregatory and anticarcinogenic properties, and modulation of lipoprotein metabolism.
Mutant dwarf and calorie-restricted mice benefit from healthy aging and unusually long lifespan. In contrast, mouse models for DNA repair-deficient progeroid syndromes age and die prematurely. To identify mechanisms that regulate mammalian longevity, we quantified the parallels between the genome-wide liver expression profiles of mice with those two extremes of lifespan. Contrary to expectation, we find significant, genome-wide expression associations between the progeroid and long-lived mice.
Calorie restriction (CR) produces several health benefits and increases lifespan in many species. Studies suggest that alternate-day fasting (ADF) and exercise can also provide these benefits. Whether CR results in lifespan extension in humans is not known and a direct investigation is not feasible. However, phenotypes observed in CR animals when compared to ad libitum fed (AL) animals, including increased stress resistance and changes in protein expression, can be simulated in cells cultured with media supplemented with blood serum from CR and AL animals.
Current Opinion in Investigational Drugs (London, England: 2000)
SIRT1 (sirtuin 1) is the human ortholog of the yeast Sir2 (silent information regulator 2) protein, which is implicated in lifespan extension in model organisms, such as yeast, worms and flies. It is an NAD+-dependent protein deacetylase with over two dozen known substrates that affect a wide variety of cellular processes, ranging from metabolism, cell cycle, growth and differentiation, inflammation, senescence, apoptosis, stress response and aging.
This review focuses on research involving calorie restriction (CR) in humans and the resulting changes observed in endocrine and neuroendocrine systems. Special emphasis is given to the clinical science studies designed to investigate the effects of controlled, high-quality, energy-restricted diets on both biomarkers of longevity and on the development of chronic diseases of human aging. Prolonged CR has been shown to extend both the median and maximal lifespan in a variety of lower species such as yeast, worms, fish, rats and mice.