title: Converging pathways in lifespan regulation.
abstract: The processes that determine an organism's lifespan are complex and poorly understood. Yet single gene manipulations and environmental interventions can substantially delay age-related morbidity. In this review, we focus on the two most potent modulators of longevity: insulin/insulin-like growth factor 1 (IGF-1) signaling and dietary restriction. The remarkable molecular conservation of the components associated with insulin/IGF-1 signaling and dietary restriction allow us to understand longevity from a multi-species perspective. We summarize the most recent findings on insulin/IGF-1 signaling and examine the proteins and pathways that reveal a more genetic basis for dietary restriction. Although insulin/IGF-1 signaling and dietary restriction pathways are currently viewed as being independent, we suggest that these two pathways are more intricately connected than previously appreciated. We highlight that numerous interactions between these two pathways can occur at multiple levels. Ultimately, both the insulin/IGF-1 pathway and the pathway that mediates the effects of dietary restriction have evolved to respond to the nutritional status of an organism, which in turn affects its lifespan.
authors.affiliation: Program in Gene Function and Expression, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
authors.forename: Sri Devi
authors.initials: SD
authors.lastname: Narasimhan
authors.forename: Kelvin
authors.initials: K
authors.lastname: Yen
authors.forename: Heidi A
authors.initials: HA
authors.lastname: Tissenbaum
mesh_terms: D000818:Animals; D031204:Caloric Restriction; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008136:Longevity / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D009812:Odorants; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D037761:Sirtuins / Q000378:metabolism; D013045:Species Specificity
chemical_list: D007328:Insulin; D017526:Receptor, IGF Type 1; D037761:Sirtuins
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