Identification of longevity-associated genes in long-lived Snell and Ames dwarf mice.

Age
William H BoylstonJohn Papaconstantinou

Abstract

Recent landmark molecular genetic studies have identified an evolutionarily conserved insulin/IGF-1 signal transduction pathway that regulates lifespan. In C. elegans, Drosophila, and rodents, attenuated insulin/IGF-1 signaling appears to regulate lifespan and enhance resistance to environmental stress. The Ames (Prop1 (df/df)) and Snell (Pit1 (dw/dw)) hypopituitary dwarf mice with growth hormone (GH), thyroid-stimulating hormone (TSH), and prolactin deficiencies live 40-60% longer than control mice. Both mutants are resistant to multiple forms of environmental stress in vitro. Taken collectively, these genetic models indicate that diminished insulin/IGF-l signaling may play a central role in the determination of mammalian lifespan by conferring resistance to exogenous and endogenous stressors. These pleiotropic endocrine pathways control diverse programs of gene expression that appear to orchestrate the development of a biological phenotype that promotes longevity. With the ability to investigate thousands of genes simultaneously, several microarray surveys have identified potential longevity assurance genes and provided information on the mechanism(s) by which the dwarf genotypes (dw/dw) and (df/df), and caloric restriction m...Continue Reading

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Citations

Jul 25, 2007·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Jörg IsenseePatricia Ruiz Noppinger
May 6, 2009·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Alex F BokovArlan Richardson
May 12, 2009·Mechanisms of Ageing and Development·William R SwindellRichard A Miller
Sep 18, 2013·Molecular and Cellular Biology·Gaëlle LaurentMarcia C Haigis
Nov 4, 2020·Cells·Nafiseh Chalabi Hagkarim, Roger J Grand
Mar 27, 2020·Cell Reports·Mingyi YangMagnar Bjørås
Apr 14, 2021·GeroScience·Rachana TrivediDonald A Jurivich

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