Ageing in Drosophila: the role of the insulin/Igf and TOR signalling network.
A remarkable discovery of recent years is that, despite the complexity of ageing, simple genetic interventions can increase lifespan and improve health during ageing in laboratory animals. The pathways involved have often proved to sense nutrients and to match costly activities of organisms, such as growth, metabolism and reproduction, to nutrient status. For instance, the insulin/insulin-like growth factor and Target of Rapamycin signalling network has proved to play a function in ageing, from yeast to mammals, seemingly including humans. In the fruit fly Drosophila, altered activity of several components of this network can increase lifespan and improve locomotor and cardiac function during ageing. The fly brain, fat body (equivalent of mammalian liver and white adipose tissue) and the germ line are important in determination of lifespan, with considerable communication between different tissues. Cellular detoxification pathways, increased autophagy and altered protein synthesis have all been implicated in increased lifespan from reduced IIS/TOR activity, with the role of defence against oxidative stress unresolved. Reduced IIS/TOR signalling can alter or block the response of lifespan to dietary restriction. Reduced IIS can act acutely to lower death rate, implying that it may ameliorate the effects of ageing-related damage, rather than preventing it.
Partridge
Linda
L
Institute of Healthy Ageing, London, WC1E 6BT, UK. l.partridge@ucl.ac.uk
Alic
Nazif
N
Bjedov
Ivana
I
Piper
Matt D W
MD
D000375:Aging / Q000502:physiology*; D000818:Animals; D029721:Drosophila Proteins / Q000502:physiology*; D004331:Drosophila melanogaster / Q000502:physiology*; D007328:Insulin / Q000502:physiology*; D023421:Models, Animal; D011494:Protein Kinases / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013002:Somatomedins / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases
D029721:Drosophila Proteins; D007328:Insulin; D013002:Somatomedins; D011494:Protein Kinases; C416303:target of rapamycin protein, Drosophila; D058570:TOR Serine-Threonine Kinases