Abstract
Caloric restriction is the most effective and reproducible dietary intervention known to regulate aging and increase the healthy lifespan in various model organisms, ranging from the unicellular yeast to worms, flies, rodents, and primates. However, caloric restriction, which in most cases entails a 20–40% reduction of food consumption relative to normal intake, is a severe intervention that results in both beneficial and detrimental effects. Specific types of chronic, intermittent, or periodic dietary restrictions without chronic caloric restriction have instead the potential to provide a significant healthspan increase while minimizing adverse effects. Improved periodic or targeted dietary restriction regimens that uncouple the challenge of food deprivation from the beneficial effects will allow a safe intervention feasible for a major portion of the population. Here we focus on healthspan interventions that are not chronic or do not require calorie restriction.
Highlights
Aging is the leading risk factor for many among the major diseases and a key factor in the overall decline of physical and mental performance
Here, we use caloric restriction (CR) to refer to a dietary intervention with an overall 20–40% reduction of total caloric intake, and dietary restriction to represent a broader scope of dietary interventions that encompass those with specific macronutrient and feeding pattern restrictions
CR is the most studied and reproducible non-genetic intervention known to extend healthspan and/or lifespan in organisms, ranging from unicellular yeast to monkeys. It started with a simple experiment where a reduction in dietary intake extended the lifespan of rats[1], providing a foundation to experimentally study the relationship between nutrition and the biology of aging
Summary
Aging is the leading risk factor for many among the major diseases and a key factor in the overall decline of physical and mental performance. Dietary restriction: macromolecular restriction without caloric restriction The definition of dietary restriction has been expanded from an alternative description of caloric restriction to encompass a broader scope of interventions, including short-term starvation, periodic fasting, fasting-mimetic diets, intermittent fasting, normocaloric diets with planned deficiencies (in particular macronutrients: proteins, carbohydrates, etc.), and time-restricted feeding Most of these relatively novel interventions are reported to have beneficial effects on overall health and in some cases longevity. Caloric restriction and fasting share similar but often distinct effects on a number of biomarkers (e.g. reduced glucose, and insulin levels) suggesting that partially overlapping mechanisms are involved[19] Both intermittent and periodic fasting can increase lifespan, even when there is little or no overall decrease in calorie intake[34,50]. C o n s i d e r i n g t h a t k e y m e t a b o l i c fa c to r s , s u c h as 5’ AMP-activated protein kinase (AMPK), sirtuins, and protein kinase B (AKT), are regulated by an interplay of circadian rhythm and feeding time[54,55], dietary schedules should be more carefully studied in the context of dietary restriction
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