Antiaging diets: Separating fact from fiction

Abstract

Caloric restriction has been known for nearly a century to extend life span and delay age-associated pathology in laboratory animals. More recently, alternative “antiaging” diet modalities have been described that provide new mechanistic insights and potential clinical applications. These include intermittent fasting, fasting-mimicking diets, ketogenic diets, time-restricted feeding, protein restriction, and dietary restriction of specific amino acids. Despite mainstream popularization of some of these diets, many questions remain about their efficacy outside of a laboratory setting. Studies of these interventions support at least partially overlapping mechanisms of action and provide insights into what appear to be highly conserved mechanisms of biological aging.

Figure 1.

Percent lifespan change on restricted compared to unrestricted diet for genetically distinct strains of model organisms. In every case, each bar along the x-axis represents a unique genetic background and the percent change in lifespan of that strain in response to dietary restriction is shown on the y-axis. A) Change in mean lifespan for recombinant-inbred female (red) and male (blue) mice under ad libitum and 40% caloric restriction (CR) diets (67). B) Change in median lifespan in genetically variable female flies from a natural population under a 10-fold protein restriction (69, 70). C) Change in mean lifespan for single gene deletion mutant yeast under a 40-fold glucose restriction (68). Organism cartoons created using Biorender.com.

Figure 2.

Diet modalities, molecular mechanisms, and downstream consequences of anti-aging diets. Dietary interventions that impact aging in mice limit one or more of the major dietary macromolecules and elicit cellular responses via a complex nutrient sensing network. Key components of this network which have been implicated in effects on lifespan and healthspan in various laboratory model organisms include mechanistic Target Of Rapamycin (mTOR), Fibroblast Growth Factor 21 (FGF21), Adenosine Monophosphate-activated Protein Kinase (AMPK), insulin/Insulin Growth Factor 1 (IGF-1) receptors, AK strain Transforming (AKT), sestrin, and sirtuins. Figure created using Biorender.com.