Genetic variation of dietary restriction and the effects of nutrient-free water and amino acid supplements on lifespan and fecundity ofDrosophila

Abstract

We measure genetic variation in lifespan and fecundity at two food levels in 34 core lines of the Drosophila Genetic Reference Panel collection. Lines were significantly different from each other in lifespan and fecundity at both restricted and full food. There was a strong food-by-line interaction for the slope of age-specific mortality, fecundity and proportion of fertilized eggs, indicating the presence of genetic variation for the strength of the dietary restriction effect, likely to represent standing genetic variation in a natural population from which the lines used have originated. No trade-off between fecundity and lifespan manifested in life-history variation among inbred lines. Our data partially corroborate the recent proposition that availability of nutrient-free water eliminates the apparent dietary restriction at least in some conditions. Although flies on full food with water added had lifespan slightly higher than those without a water source, it was still significantly lower than that in flies on restricted food, with no indication of interaction. We fully corroborate the recently discovered effect of addition of essential amino acids to the medium: addition of 1.5 mM methionine to restricted food significantly increased fecundity without a measurable decrease in lifespan; addition of each of 10 essential amino acids increased fecundity and decreased females lifespan to the levels observed on full food, again with no evidence of line-by-food interactions. We propose a mechanistic hypothesis explaining the observed data, based on the assumption that food consumption by flies is adjusted according to flies' saturation in water and methionine.

Interactive effects of sex, social environment, dietary restriction, and methionine on survival and reproduction in fruit flies

“…These results differ from previous studies that found methionine to have a fecundityrestoring effect when fed to once-mated females (Dick et al 2011;Kabil et al 2011). Grandison et al (2009a) showed this with a concentration of methionine comparable to the one we used (0.7 mM), while the other studies got this result using a higher concentration (1.5 mM) of methionine (Dick et al 2011;Kabil et al 2011). Concentration of methionine could, therefore, potentially explain some of the discrepancy between results.…”

“…In fact, males in mixed-sex groups on restricted diets without methionine had lower average lifespan compared to the 1.0 diet. In contrast, other studies have found a positive effect of DR on male lifespan (Magwere et al 2004;Bross et al 2005;Dick et al 2011). As it stands, we Further studies are necessary to confirm this finding, but our results highlight that nutritional effects can be sex-specific and that it is possible for lifespan-extending genetic or environmental manipulations to be only successful in one sex, with a negative or no effect on the other sex.…”

“…Males are rarely used in Drosophila aging studies but see (Magwere et al 2004;Bross et al 2005;Dick et al 2011) and almost never in different social environments. In our study, males on restricted diets did not have higher average lifespan compared to the 1.0 diet.…”

“…These interventions range from single-gene alterations (Fontana et al 2010;Magwire et al 2010) to dietary compounds that are directly implicated in basic cellular processes (Bjedov et al 2010) or compounds that potentially mimic the lifespanextending effect of DR (Valenzano et al 2006). Out of the second mentioned category, the effect of dietary methionine on lifespan has been examined in some detail (Troen et al 2007;Grandison et al 2009a;Dick et al 2011;Kabil et al 2011). Methionine is an essential amino acid that is involved in a very wide range of cellular processes.…”

Amino acid modulation of lifespan and reproduction in Drosophila

“…While adding back all EAA (DR + EAA) shortened lifespan and restored fecundity, adding back all EAA minus methionine (DR + EAA À M) failed to shorten lifespan, indicating that methionine restriction can promote longevity. Remarkably, by manipulating each EAA individually Grandison and coauthors found that adding methionine alone to the restricted diet (DR + M) restores fecundity to normal levels but without reducing the long lifespan of DR flies (also see [21]). These findings suggest that methionine is -at least partly -responsible for the lifespan-shortening effect of full feeding, even though methionine alone (DR + M) might be insufficient to reduce longevity.…”