Caloric Restriction May Increase Longevity

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.

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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.

Cellular health

When you reduce calorie intake through caloric restriction, your body adapts by optimizing energy production. During periods of caloric restriction, the body relies on stored energy reserves, such as glycogen and fat. This process involves enhanced mitochondrial function, which is crucial for cellular energy production. Mitochondria are cellular structures responsible for generating adenosine triphosphate (ATP), the primary energy currency of cells.

Caloric restriction can lead to a decrease in oxidative stress within cells. Oxidative stress occurs when there is an imbalance between harmful free radicals and the body's antioxidant defenses. Caloric restriction may enhance the body's ability to counteract oxidative damage, which can help maintain cellular health.

Research in various organisms, including yeast, worms, flies, and mice, has demonstrated that caloric restriction can extend lifespan. While the evidence for significant lifespan extension in humans is limited, Caloric restriction may contribute to a longer and healthier life by delaying age-related diseases and promoting cellular health.

Autophagy is a cellular process that removes damaged or dysfunctional components, including organelles and proteins, to maintain cellular integrity and function. Caloric restriction has been shown to stimulate autophagy, which helps rejuvenate cells by clearing out cellular debris.

Evidences Suggest That Caloric Restriction Can Provide Benefits To Humans

Until not long ago, it was an open question whether the beneficial effects of caloric restriction can be seen in our closest relatives, the primates. The conclusions of a recent study conducted in rhesus monkeys have now shed some light on this question.  

More studies are needed to understand how macro- and micro-nutrients, endurance exercise, and other environmental and psychological factors interact with caloric restriction in modulating the metabolic and molecular pathways that regulate health and longevity. Both excessive dietary restriction and over-nutrition are different forms of malnutrition that lead to organ dysfunction and increased mortality. Just last year, scientists demonstrated that the lifelong caloric restriction aggravated the age-related loss of spontaneous motor activity and the increase of anxiety-like behavior. Conversely, the same researchers reported, for the first time, that lifelong caloric restriction increases spatial learning and working memory.

The benefits of caloric restriction in humans are not yet fully proven

Owing to ethical and experimental limitations, randomized, caloric restriction-controlled, long-term survival studies in humans have not been actively conducted and it is unlikely that they will ever be done.

However, a modest calorie restriction is a commonly used strategy in cardiac rehabilitation programs, especially when combined with exercise training. The benefits of modest calorie restriction, irrespective of the dietary composition, are such that it should continue to be part of a combined lifestyle program to improve cardiometabolic health, for instances. In recent studies conducted in overweight humans, caloric restriction has been shown to improve a number of health outcomes including reducing several cardiac risk factors, improving insulin-sensitivity and enhancing mitochondrial function.

See Also: Fasting For A Long, Healthy Life

A key issue for the future research examining the effects of caloric restriction in humans is whether or not the promising findings from initial human trials translate to non-overweight individuals whose body mass index falls in the healthy range. This possibility is currently being explored by the CALERIE Phase 2 study. Specifically, the CALERIE Phase 2 study is examining the long-term effects of a 25% reduction of ad libitum energy intake in non-obese, middle-aged men and women (21–50 years) on markers of aging, cardiovascular disease risk, insulin sensitivity and secretion, immune function, neuroendocrine function, quality of life, and cognitive function.