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Regulation of C. elegans life-span by insulinlike signaling in the nervous system. Science 290, 147-150

Department of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
Science (Impact Factor: 31.48). 11/2000; 290(5489):147-50.
Source: PubMed

ABSTRACT An insulinlike signaling pathway controls Caenorhabditis elegans aging, metabolism, and development. Mutations in the daf-2 insulin receptor-like gene or the downstream age-1 phosphoinositide 3-kinase gene extend adult life-span by two- to threefold. To identify tissues where this pathway regulates aging and metabolism, we restored daf-2 pathway signaling to only neurons, muscle, or intestine. Insulinlike signaling in neurons alone was sufficient to specify wild-type life-span, but muscle or intestinal signaling was not. However, restoring daf-2 pathway signaling to muscle rescued metabolic defects, thus decoupling regulation of life-span and metabolism. These findings point to the nervous system as a central regulator of animal longevity.

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    • "Dauer pathway is an altered pathway of development of C. Elegans, and Dauer individuals have prolonged lifespans. Dauer pathway was found to be induced by an environment change and be mediated by insulin-like signaling pathway (Wolkow et al, 2000). Hormones and hormone-related genes were then thought to be important in regulating aging process apart from regulating development (de Magalhaes et al, 2005). "
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    • "The insulin signaling pathway is a central regulator of longevity in both invertebrates and vertebrates (Wolkow et al., 2000; Tatar et al., 2003; Kenyon, 2005; Greer and Brunet, 2008; Broughton and Partridge, 2009; Kenyon, 2010; Barzilai et al., 2012). Single-gene loss-of-function mutations in insulin signaling components extend lifespan in Caenorhabditis elegans and D. melanogaster, and loss of insulin signaling activity in specific tissues of mice can also promote longevity. "
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    • "The IIS pathway plays an endocrine role to modulate lifespan in a cell-nonautonomous manner. Genetic mosaics lacking daf-2 in neuronal precursor cells are long-lived (Apfeld and Kenyon, 1998), and neuronal expression of daf-2 rescues the daf-2 mutant-mediated lifespan extension (Wolkow et al., 2000). However , the essential IIS downstream transcription factor DAF-16 functions mainly in the intestine to modulate longevity (Libina et al., 2003). "
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