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

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 y...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2018-01, Vol.13 (1), p.e0190105-e0190105
Main Authors: Mason, Janet S, Wileman, Tom, Chapman, Tracey
Format: Article
Language:English
Subjects:
Analysis
Animal life cycles
Animals
Autophagy
Autophagy (Cytology)
Biology and Life Sciences
Cell death
Diet
Drosophila
Drosophila melanogaster
Drosophila melanogaster - physiology
Fecundity
Female
Females
Fertility
Genetic aspects
Infertility
Life span
Longevity
Male
Medicine and Health Sciences
Naphthyridines - administration & dosage
Nutrition
Phagocytosis
Physiological aspects
Rapamycin
TOR protein
Tradeoffs
Yeast
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0190105