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We live much longer than our closest relatives in the animal kingdom. In spite of the many characteristics that human and non-human primates have in common, such as anatomical, physiological and behavioral attributes, humans stand out from their counterparts not only with respect to cognition or bipedal locomotion, but also with respect to maximal lifespan. 90% of our closest living relatives, the common chimpanzees, die before the age of 40. By contrast, it is nowadays not uncommon for men and women to overcome the mark of the 80 or 90 years of age.
How lifespan can be extended?
Aging is associated with a host of biological changes that contribute to a progressive decline in cognitive and physical function, ultimately leading to a loss of independence and increased risk of mortality.
Mortality and age-related functional decline is dependent on a number of physiological processes, such as immune response, DNA damage repair mechanisms, metabolic pathways, etc. The secrets for longevity have been researched all over the globe. Pharmaceutical, genetic and environmental interventions have been tested and some have yielded excellent results, increasing the lifespan of laboratory animals by as much as 10-fold.
Caloric restriction helps to extend lifespan in animals
Perhaps the best-studied, most robust intervention of all is caloric restriction. Caloric restriction is a type of dietary regime that involves reducing calorie intake by 10-40% compared to a dietary regime where there is no restriction on calorie intake. An initial report, published in 1994, showed that underfed rats lived longer than rats fed ad libitum. This sparked an intense wave of research on the subject. Nowadays, there is little doubt about its effectiveness, as numerous investigations have proved that reduced calorie intake without, of course, malnutrition, extends lifespan in various species, from yeast to fruit flies and even rodents.
Caloric restriction leads to multiple physiological responses
But why does caloric restriction increase longevity? The assumption almost appears paradoxical. What seems to happen in a state of caloric restriction is that the body moves from its usual state of cell death-growth-proliferation and back again to a state of maintenance and repair. Physiological responses to caloric restriction include decrease in metabolic rate, hypothermia (reduction in the normal body temperature) and overall reduction in the transmission of nervous impulses to multiple regions, including adipose tissue, a reduction in heart rate and a decrease in blood pressure. From a genetic point of view, caloric restriction has the power to alter the expression levels of hundred of genes involved in a number of biological processes, like growth, sugar and lipid metabolism, the immune system and more.
Reduction of oxidative stress is key benefit of caloric restriction
The most reliable hypothesis of anti-aging effect of caloric restriction is associated with the reduction of oxidative stress. Oxygen that enters the body is changed into reactive oxygen species through cellular respiration, which subsequently attacks various molecules in the cells such as proteins and DNA, resulting in the onset of age-associated changes.
Numerous studies have supported this hypothesis. However, there is also considerable controversy associated with it.
In rodents, the caloric restriction-mediated preventive effects are widespread with major reductions in the occurrence and/or progression of cancer, nephropathy, cardiomyopathy, obesity, type 2 diabetes, neurodegenerative disease, and several autoimmune diseases. Moreover, unlike ad libitum fed rodents, about 30% of the rodents on caloric restriction diets die in old age without any pathological sign of disease. This type of evidence suggests that in mammals the occurrence of lethal chronic disease can be completely prevented by dietary and genetic manipulations that down-regulate the key cellular nutrient-sensing pathways.