McCracken, A. W. | bioRxiv Science

bioRxiv2020

The relationship between longevity and diet is genotype dependent and sensitive to desiccation

Dietary restriction (DR) is a key focus in ageing research. Specific conditions and genotypes were recently found to negate lifespan extension by DR, questioning its universal relevance. However, the conceptual framework of dietary reaction norms explains why DRs effects might not be apparent in some situations. We tested comprehensively the importance of dietary reaction norms by measuring longevity and fecundity on five diets in five genotypes, with and without water supplementation in the fly (N>25,000). We found substantial genetic variation in the reaction norm between diet and lifespan. Environments supplemented with water rescued putative desiccation stress but only at the richest diets. Fecundity declined at these richest diets, but was unaffected by water and is thus most likely caused by nutritional toxicity. Our results demonstrate empirically that any conclusion on the absence of DR is only justified when a range of diets is considered in a reaction norm framework.

evolutionary biology↗

bioRxiv2019

The hidden costs of dietary restriction: implications for its evolutionary and mechanistic origins

Dietary restriction (DR) consistently and universally extends health-and lifespan across taxa. Despite efforts to uncover the mechanisms underpinning DR - and ultimately translate its beneficial outcomes to humans - precise and universal mechanisms have not been identified. In biomedical science, the effects of DR are interpreted as regulating pro-longevity molecular pathways. This reasoning is guided by the conviction that DR evolved as an adaptive, pro-longevity physiological response to restricted food intake. Current evolutionary theory states that organisms should invest in their soma more heavily during periods of DR, and, when their resource availability improves, should outcompete age-matched rich-fed controls in survival and/or reproduction. Here we present a formal test of these key predictions utilising a large-scale demographic approach detailing mortality and fecundity in Drosophila melanogaster fed alternating dietary regimes (N > 66,000 flies across 11 genetic lines). Our experiments reveal surprising and substantial mortality costs when returning to a rich diet after periods of DR. These results suggest the effects of DR are not necessarily intrinsically pro-longevity and could be considered an escape from costs incurred under nutrient-rich conditions, in addition to novel, discrete costs associated with restricting dietary protein. These insights question the relevance of current evolutionary explanations of DR in interpreting the mechanistic basis of dietary restriction.

evolutionary biology↗