Data: Neither caloric nor protein restriction increases the lifespan of outbred short-lived fish

Dietary restriction (DR) extends lifespan across various species, but with population-specific responses. While laboratory inbred strains respond strongly to DR, genetically diverse populations may not see the same advantages. In addition, the understanding of an efficient form of dietary restriction shifted from general calorie reduction to specifically targeting certain macronutrients, warranting study of their relative importance. The exceptionally short-lived fish, <i>Nothobranchius furzeri</i>, offers several genetically distinct captive populations, but only the severely inbred GRZ strain was tested for possible benefits arising from caloric restriction, with intermittent fasting extending their lifespan. Here, individually kept males (N=111) of the genetically diverse MZCS222 strain of <i>N. furzeri</i> were assigned to 1/ high-protein diet and two DR forms: 2/ low-protein (isocaloric to high-protein but half the protein concentration), or 3/ caloric-restriction (half the dose of HP at the feeding time). Neither form of DR significantly extended the lifespan of genetically diverse <i>N. furzeri</i>. This finding indicates the limited efficacy of dietary restrictions in genetically diverse populations, underscoring the need for further exploration of the complex interactions between diet, growth, genetics, and longevity.