Reconciling nutritional geometry with classical dietary restriction: Effects of nutrient intake, not calories, on survival and reproduction

Abstract

Dietary restriction (DR) is one of the main experimental paradigms to investigate the mechanisms that determine lifespan and aging. Yet, the exact nutritional parameters responsible for DR remain unclear. Recently, the advent of the geometric framework of nutrition (GF) has refocussed interest from calories to dietary macronutrients. However, GF experiments focus on invertebrates, with the importance of macronutrients in vertebrates still widely debated. This has led to the suggestion of a fundamental difference in the mode of action of DR between vertebrates and invertebrates, questioning the suggestion of an evolutionarily conserved mechanism. The use of dietary dilution rather than restriction in GF studies makes comparison with traditional DR studies difficult. Here, using a novel nonmodel vertebrate system (the stickleback fish, Gasterosteus aculeatus), we test the effect of macronutrient versus calorie intake on key fitness‐related traits, both using the GF and avoiding dietary dilution. We find that the intake of macronutrients rather than calories determines both mortality risk and reproduction. Male mortality risk was lowest on intermediate lipid intakes, and female risk was generally reduced by low protein intakes. The effect of macronutrient intake on reproduction was similar between the sexes, with high protein intakes maximizing reproduction. Our results provide, to our knowledge, the first evidence that macronutrient, not caloric, intake predicts changes in mortality and reproduction in the absence of dietary dilution. This supports the suggestion of evolutionary conservation in the effect of diet on lifespan, but via variation in macronutrient intake rather than calories.

Factors that affect the translation of dietary restriction into a longer life

“…Macronutrient restriction and restrictions in food availability are DR regimens that have repeatedly been shown to prolong lifespan. Numerous different diets that are restricted with regard to particular macronutrients have been described, but those characterized by substantially lower protein content are of particular interest because they have been reproducibly associated with longer life . Indeed, it has been hypothesized that the beneficial effects of CR on lifespan can be attributed mainly to the associated reduction in protein intake; however, this view has recently been challenged .…”

“…Traditionally, lifespan extension has been attributed to the lower energy contribution of CR diets . However, studies performed in yeast, Drosophila and other invertebrate models have focused on the importance of reducing the protein content of the diet, and consequently it has been concluded that protein restriction is the most important component of a CR regimen for its lifespan‐extending effects. However, recent analyses have challenged this view and claimed that, at least in rodents, it is the lower energy contribution of a CR diet that is causally linked to lifespan extension, rather than protein restriction .…”

“…However, recent analyses have challenged this view and claimed that, at least in rodents, it is the lower energy contribution of a CR diet that is causally linked to lifespan extension, rather than protein restriction . These seemingly conflicting results were obtained in studies carried out using different models: groups working with invertebrates have repeatedly identified protein restriction as causing lifespan extension, whereas other groups working with rodents have identified energy restriction as the cause . This has led to the hypothesis that the mechanism of lifespan extension resulting from nutrient restriction (energy or protein) is not phylogenetically conserved .…”

“…This has led to the hypothesis that the mechanism of lifespan extension resulting from nutrient restriction (energy or protein) is not phylogenetically conserved . However, this view has been contradicted by more recent work demonstrating extensive similarities between vertebrates and invertebrates with regard to lifespan extension …”

“…Numerous different diets that are restricted with regard to particular macronutrients have been described, but those characterized by substantially lower protein content are of particular interest because they have been reproducibly associated with longer life. [9][10][11] Indeed, it has been hypothesized that the beneficial effects of CR on lifespan can be attributed mainly to the associated reduction in protein intake 11,12 ; however, this view has recently been challenged. 13 Nevertheless, studies performed in a number of animal species have shown that protein restriction increases both lifespan and healthy lifespan, implying that these effects involve evolutionarily conserved mechanisms that might also be operational in humans.…”