Does diet influence aging? Evidence from animal studies

Abstract

Nutrition profoundly influences the risk for many age-related diseases. Whether nutrition influences human aging biology directly is less clear. Studies in different animal species indicate that reducing food intake ("caloric restriction" [CR]) can increase lifespan and delay the onset of diseases and the biological hallmarks of aging. Obesity has been described as "accelerated aging" and therefore the lifespan and health benefits generated by CR in both aging and obesity may occur via similar mechanisms. Beyond calorie intake, studies based on nutritional geometry have shown that protein intake and the interaction between dietary protein and carbohydrates influence age-related health and lifespan. Studies where animals are calorically restricted by providing free access to diluted diets have had less impact on lifespan than those studies where animals are given a reduced aliquot of food each day and are fasting between meals. This has drawn attention to the role of fasting in health and aging, and exploration of the health effects of various fasting regimes. Although definitive human clinical trials of nutrition and aging would need to be unfeasibly long and unrealistically controlled, there is good evidence from animal experiments that some nutritional interventions based on CR, manipulating dietary macronutrients, and fasting can influence aging biology and lifespan.

Keywords: aging; caloric restriction; fasting; nutritional geometry; obesity.

Fig. 1

Macronutrients and lifespan in (a) mice and (b) Drosophila. In these studies, Drosophila and mice had ad libitum access to one of 28 and 25 diets, respectively, varying in macronutrients and energy content. Lifespan data are presented as heatmaps ranging from blue (lowest values) to red (highest values). Drosophila diet has two macronutrients, protein and carbohydrates; therefore, one heatmap is shown with the axes representing the intake of carbohydrate or protein. In mice, there are three macronutrients—protein, carbohydrates, and fat; therefore, three heatmaps are presented, each having two macronutrients for the x and the y axes, at the median value of the other macronutrient. In both Drosophila and mice, the highest lifespan (red area of heatmaps) was the longest with diets that were higher in carbohydrates, lower in protein, and where the energy intake was higher (adapted from Lee et al. [155] and Solon-Biet et al. [16]).

Fig. 2

Macronutrients and (a) telomere length in the liver, (b) FGF21 levels, (c) IGF-1 levels, (d) phosphorylated mechanistic target of rapamycin (MTOR) in the liver, and (e) insulin levels. Data are presented as heatmaps ranging from blue (lowest values) to red (highest values). Three heatmaps are presented, each having two macronutrients for the x and the y axes, at the median value of the other macronutrient.

Fig. 3

Aging, obesity, and calorie intake. Obesity can be considered to be accelerated aging with reduced lifespan, increased body fat, abnormal glucose/insulin metabolism, and increased evidence of the Hallmarks of Aging. Caloric restriction (and fasting) causes delayed aging and has the opposite effect on these parameters. Reproductive function is reduced by both caloric restriction and obesity; therefore, its optimum diet and body weight must be at some point in between (U-shaped relationship). It should be noted that (1) these are biomedical endpoints pertaining to model systems and (2) the relationship between obesity and aging can also be influenced by the macronutrient composition of the diets.