ReviewSignalling and autophagy regulation in health, aging and disease
Section snippets
Autophagy in aging
More and more evidence has been accumulating in recent years indicating that both caloric restriction (Cuervo et al., 2005) and defective insulin signalling (Tatar et al., 2003, Katic and Kahn, 2005) extend life-span. Presumably, this can be ascribed, at least in part, to increased autophagy (Melendez et al., 2003, Cuervo et al., 2005). It is perhaps not by accident that the Klotho protein which has strong anti-aging properties in mammals confers insulin resistance (Kurosu et al., 2005).
Cancer
As discussed earlier, the amino acid signalling pathway oppositely controls protein synthesis and autophagy. Evidently, overactivation of the amino acid signalling pathway leads to overactivation of protein synthesis and thus contributes to cancer cell growth. The notion that suppression of autophagy can also contribute is not generally known but evidence in support of this is rapidly growing (Levine and Klionsky, 2004, Kondo et al., 2005, Ng and Huang, 2005, Hait et al., 2006, Botti et al.,
Potential implication of autophagy in other diseases
Finally, we want to discuss two pathologies (type-2 diabetes and hepatic encephalopathy) in which autophagy may play an important role although this has not been studied yet.
Acknowledgements
Work in P. Codogno’s laboratory is supported by institutional funding from The Institut National de la Santé et de la Recherche Médicale (INSERM), University of Paris-Sud and grants from the Association pour la Recherche sur le Cancer (ARC 3503).
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