Lifespan extension without fertility reduction following dietary addition of the autophagy activator Torin1 in Drosophila melanogaster

Abstract

Autophagy is a highly conserved mechanism for cellular repair that becomes progressively down-regulated during normal ageing. Hence, manipulations that activate autophagy could increase lifespan. Previous reports show that manipulations to the autophagy pathway can result in longevity extension in yeast, flies, worms and mammals. Under standard nutrition, autophagy is inhibited by the nutrient sensing kinase Target of Rapamycin (TOR). Therefore, manipulations of TOR that increase autophagy may offer a mechanism for extending lifespan. Ideally, such manipulations should be specific and minimise off-target effects, and it is important to discover additional methods for ‘clean’ lifespan manipulation. Here we report an initial study into the effect of up-regulating autophagy on lifespan and fertility in Drosophila melanogaster by dietary addition of Torin1. Activation of autophagy using this selective TOR inhibitor was associated with significantly increased lifespan in both sexes. Torin1 induced a dose-dependent increase in lifespan in once-mated females. There was no evidence of a trade-off between longevity and fecundity or fertility. Torin1-fed females exhibited significantly elevated fecundity, but also elevated egg infertility, resulting in no net change in overall fertility. This supports the idea that lifespan can be extended without trade-offs in fertility and suggest that Torin1 may be a useful tool with which to pursue anti-ageing research.

Autophagy Activator Drugs: A New Opportunity in Neuroprotection from Misfolded Protein Toxicity

“…Among these, an interesting novel compound, although pharmacokinetically limited, is Torin1 which is able to inhibit the kinase domain of both TORC complexes in a highly specific manner, without appreciable effects on PI3K [ 167 ]. Recently, Torin1 demonstrated anti-aging capacity as a dietary supplement in a fly model without altering other parameters that may influence lifespan [ 168 ].…”

The GATA transcription factor Gaf1 represses tRNA genes, inhibits growth, and extends chronological lifespan downstream of fission yeast TORC1

“…Torin1 increases lifespan in flies (Mason et al, 2018) and suppresses senescence in human tissue cultures (Leontieva and Blagosklonny, 2016). To analyze the effect of Torin1 on chronological lifespan in fission yeast, and any role of Gaf1 in this condition, we pre-treated exponentially growing wild-type and gaf1Δ cells with Torin1 and tested for subsequent effects on lifespan during stationary phase.…”

Effect of the Resveratrol Rice DJ526 on Longevity

“…This study showed that feeding D. melanogaster with the resveratrol rice DJ526 extended the fly lifespan by as much as 41.4%. Although various studies are reporting the extension of the D. melanogaster lifespan [37,38,39,40,41,42,43], no chemicals or nutrients have been successfully extended the lifespan of D. melanogaster by as much as the resveratrol rice in this work.…”