Forever young and healthy? Lifespan and healthspan effects of caloric restriction mimetics

Caloric restriction (CR) is defined as a significant, sustained reduction of continued caloric intake from baseline levels. To date, CR is the most thoroughly and successfully researched method to increase both - lifespan and healthspan - in a broad range of animals and non-human primates.

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There is no direct human evidence of lifespan extension in humans from CR, yet. But the reduction of caloric intake by 30‒40% in animal models resulted in longevity increases by 40% or more. The health benefits of chronic caloric restriction resulting in lifespan extension are well established in many short-lived species.

As reported in Nature in 2018 (Pifferi, F., Terrien, J., Marchal, J. et al. Caloric restriction increases lifespan but affects brain integrity in grey mouse lemur primates. Commun Biol 1, 30 (2018) a cohort of grey mouse lemurs (Microcebus murinus, lemurid primate) was exposed to a chronic moderate (30%) caloric restriction. Compared to control animals, caloric restriction extended lifespan by 50% (from 6.4 to 9.6 years, median survival), reduced aging-associated diseases, and preserved loss of brain white matter in several brain regions.

However, caloric restriction accelerated the loss of grey matter throughout much of the cerebrum. Cognitive and behavioral performances were, however, not modulated by caloric restriction.

Chronic moderate caloric restriction can extend the lifespan and healthspan of a primate, but it seems to affect brain grey matter integrity without affecting cognitive performances.

The NIA (National Institute of Ageing) funded CALERIE study revealed significant reductions in risk factors for age-related diseases such as cardiovascular disease, diabetes, some cancers from moderate CR.

CR has been defined as a long-term 30‒40% reduction in calories, but some health benefits in humans have already been observed at less-restrictive caloric reduction levels ranging from 16 to 25 percent and time periods ranging from weeks to months.

The exact mechanisms as to how and why CR works in humans are not yet fully understood. But research points to the direction that CR may reduce oxidative damage, increasing cellular repair, lowering the production of inflammatory cytokines, or by promoting hormesis, a mild form of stress that stimulates cellular protection. CR in humans also reduces fasting insulin levels and lowers resting body temperature, two important biomarkers for delaying aging.

By the way: The frequency of meals seems to be of no relevance for CR to work, at least in animal models. Lifespan extensions in rodents have been observed at meal frequencies ranging from six times per day to three times per week.

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