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http://crossmark.crossref.org/dialog/?doi=10.1007/s10522-016-9670-8&domain=pdf
Web End = Biogerontology (2017) 18:3553 DOI 10.1007/s10522-016-9670-8
http://crossmark.crossref.org/dialog/?doi=10.1007/s10522-016-9670-8&domain=pdf
Web End = REVIEW ARTICLE
Insulin/insulin-like growth factor-1 signalling (IIS) based regulation of lifespan across species
Rebecca Mathew . Manika Pal Bhadra . Utpal Bhadra
Received: 24 August 2016 / Accepted: 25 November 2016 / Published online: 18 January 2017 Springer Science+Business Media Dordrecht 2017
Abstract An organisms well-being is facilitated by numerous molecular and biochemical pathways that ensure homeostasis within cells and tissues. Aging causes a gradual let-down in the maintenance of homeostasis due to various endogenous and environmental challenges, leading to amassing of damages, functional deterioration of different tissues and vulnerability to ailments. Nutrient sensing pathways that maintain glucose homeostasis in body are involved in regulation of aging. Insulin/insulin-like growth factor-1 (IGF-1) signalling (IIS) pathway was the rst nutrient sensing pathway discovered to affect the aging process. This pathway is highly conserved and the most studied among different organisms. Epigenetic machineries that include DNA and histone modifying enzymes and various non-coding RNAs have been identied as important contributors to nutrition-related longevity and aging control. In this report, we present the homology and differences in IIS pathway of various organisms including worm, y, rodent and human. We also discuss how epigenome
remodelling, chromatin based strategies, small and long non-coding RNA are involved to regulate multiple steps of aging or age-related insulin homeostasis. Enhanced study of the role of IIS pathway and epigenetic mechanisms that regulate aging may facilitate progressive prevention and treatment of human age-related diseases.
Keywords Insulin signalling FOXO Longevity
DNA methylation Histone modication Non-coding
RNA
Introduction
An organisms lifespan is stated as the sum of damaging changes that occur in its body and the repair and maintenance mechanisms that respond to damage (Johnson et al. 1999). Both environmental and genetic components determine the lifespan of an organism (Paaby and Schmidt 2009). After discoveries were made in the worm Caenorhabditis elegans (Kenyon et al. 1993), it was found that many genetic pathways that govern lifespan are highly conserved from nematode to human (Garofalo 2002; Holzenberger et al. 2003; Nakae et al. 2002). Loss or gain of function mutations were employed for the identication of gerontogenes (that affect aging and lifespan) and hundreds of these genes were identied (Guarente and Kenyon 2000). Insulin/IGF-1(IIS), PI3K,...