Amino Acid Availability Is Not Essential for Life-Span Extension by Dietary Restriction in the Fly

Dietary restriction (DR) is one of the most potent ways to extend health and life span. Key progress in understanding the mechanisms of DR, and aging more generally, was made when dietary protein, and more specifically essential amino acids (EAA), were identified as the dietary component to restrict to obtain DR's health and life-span benefits. This role of dietary amino acids has influenced work on aging mechanisms, especially in nutrient sensing, for example, Target of Rapamycin and insulin(-like) signaling networks. Experimental biology in Drosophila melanogaster has been instrumental in generating and confirming the hypothesis that EAA availability is important in aging. Here, we expand on previous work testing the involvement of EAA in DR through large-scale (N = 6 238) supplementation experiments across 4 diets and 2 genotypes in female flies. Surprisingly, we find that EAA are not essential to DR's life-span benefits. Importantly, we do identify the fecundity benefits of EAA supplementation suggesting the supplemented EAA were bioavailable. Furthermore, we find that the effects of amino acids on life span vary by diet and genetic line studied and that at our most restricted diet fecundity is constrained by other nutrients than EAA. We suggest that DR for optimal health is a concert of nutritional effects, orchestrated by genetic, dietary, and other environmental interactions. Our results question the universal importance of amino acid availability in the biology of aging and DR.