Insulin/IGF-like signalling, the central nervous system and aging

Broughton, Susan and Partridge, Linda (2009) Insulin/IGF-like signalling, the central nervous system and aging. Biochemical Journal, 418 (1). pp. 1-12. ISSN 0264-6021

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Abstract

Enormous strides in understanding aging have come from the discovery that mutations in single genes can extend healthy life-span in laboratory model organisms such as the yeast Saccharomyces, the fruit fly Drosophila melanogaster, the nematode worm Caenorhabditis elegans and the mouse. IIS [insulin/IGF (insulin-like growth factor)-like signalling] stands out as an important, evolutionarily conserved pathway involved in the determination of lifespan. The pathway has diverse functions in multicellular organisms, and mutations in IIS can affect growth, development, metabolic homoeostasis, fecundity and stress resistance, as well as lifespan. The pleiotropic nature of the pathway and the often negative effects of its disruption mean that the extent, tissue and timing of IIS manipulations are determinants of a positive effect on lifespan. One tissue of particular importance for lifespan extension in diverse organisms is the CNS (central nervous system). Although lowered IIS in the CNS can extend lifespan, IIS is also widely recognized as being neuroprotective and important for growth and survival of neurons. In the present review, we discuss our current understanding of the role of the nervous system in extension of lifespan by altered IIS, and the role of IIS in determination of neuronal function during aging. The nervous system can play both endocrine and cell-autonomous roles in extension of lifespan by IIS, and the effects of IIS on lifespan and neuronal function can be uncoupled to some extent. Tissue-specific manipulation of IIS and the cellular defence mechanisms that it regulates will better define the ways in which IIS affects neuronal and whole-organism function during aging.

Item Type:
Journal Article
Journal or Publication Title:
Biochemical Journal
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/1300/1303
Subjects:
?? agingcentral nervous systeminsulinbiochemistrycell biologymolecular biology ??
ID Code:
49884
Deposited By:
Deposited On:
20 Sep 2011 09:23
Refereed?:
Yes
Published?:
Published
Last Modified:
15 Jul 2024 12:20