NDLI: Insulin signaling and life span

Content Provider	Springer Nature Link
Author	Avogaro, Angelo Kreutzenberg, Saula Vigili Fadini, Gian Paolo
Copyright Year	2009
Abstract	Hyperinsulinemia and metabolic diseases are known to be associated with a reduction in life span. In the presence of insulin resistance, insulin signaling is selectively impaired, contributing to longevity shortening. Insulin indeed activates a complex web of intracellular downstream pathways, which are involved in mechanisms regulating longevity, primarily affecting cellular proliferation and apoptosis. Insulin resistance promotes reactive oxygen species (ROS) formation and favors a pro-inflammatory milieu, both these conditions playing a critical role in the reduction of life span. Insulin resistance/hyperinsulinemia also influences longevity regulating other intracellular signaling downstream in a direct or indirect manner, such as the phosphoinositide 3-kinase pathway that appears selectively impaired by insulin resistance. Decreased NAD-dependent deacetylase sirtuin (Sirt) 1 activity may mediate the shortened life span in conditions of insulin resistance. Furthermore, insulin resistance and diabetes may also associate with the telomere shortening, another important regulator of life span. This review will focus on the main intracellular pathways and mediators regulated by insulin and altered by hyperinsulinemia/insulin resistance; it summarizes the underlying mechanisms and provides evidence of these observations in experimental animal models and in human, giving further insight on the hypothesis that insulin signaling may play an important role in life span.
Starting Page	301
Ending Page	314
Page Count	14
File Format	PDF
ISSN	00316768
Journal	Pflügers Archiv
Volume Number	459
Issue Number	2
e-ISSN	14322013
Language	English
Publisher	Springer-Verlag
Publisher Date	2009-09-13
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Apoptosis Diabetes Cell death Insulin Signal transduction Human Physiology
Content Type	Text
Resource Type	Article
Subject	Physiology Physiology (medical) Clinical Biochemistry

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