Stochasticity in Dietary Restriction-Mediated Lifespan Outcomes in Drosophila

Abstract

Dietary restriction (DR) is widely considered to be one of the most potent approaches to extend healthy lifespan across various species, yet it has become increasingly apparent that DR-mediated longevity is influenced by biological and non-biological factors. We propose that current priorities in the field should include understanding the relative contributions of these factors to elucidate the mechanisms underlying the beneficial effects of DR. Our work conducted in two laboratories, represents an attempt to unify DR protocols in Drosophila and to investigate the stochastic effects of DR. Across 64 pairs of survival data (DR/ad libitum, or AL), we find that DR does not universally extend lifespan. Specifically, we observed that DR conferred a significant lifespan extension in only 26.7% (17/64) of pairs. Our pooled data show that the overall lifespan difference between DR and AL groups is statistically significant, but the median lifespan increase under DR (7.1%) is small. The effects of DR were overshadowed by stochastic factors and genotype. Future research efforts directed toward gaining a comprehensive understanding of DR-dependent mechanisms should focus on unraveling the interactions between genetic and environmental factors. This is essential for developing personalized healthspan-extending interventions and optimizing dietary recommendations for individual genetic profiles.

Figure 1.. Kaplan–Meier survival analysis of Drosophila melanogaster.

The survival curves represent the proportion of survivors over time (in days) during the adult stage. Each panel shows the survival curves for a specific factor, illustrating the effects of lab (a), dietary restriction protocol 1 (b), dietary restriction protocol 2 (c), cohorts (d), sex (e), and genotype (f) on the lifespan of the flies. These panels collectively demonstrate how different factors impact the lifespan of the flies.

Figure 2.. Correlation plot of each set of cohort pairs between the two labs.

Each point represents the mean longevity for the Hoffman lab (x-axis) or Lyu lab (y-axis) for each individual treatment, sex, genotype, lab, cohort replicate (n=64). Black line is the line of symmetry.

Figure 3.. The interaction of DR with sex (a), genotype (b), and lab (c).

Kaplan–Meier survival curves represent the proportion of survivors over time (in days) during the adult stage. Only cohorts 1–3 (DR protocol 1) were used for this analysis to control for the protocol.