Elsevier

Molecular Aspects of Medicine

Volume 27, Issues 5–6, October–December 2006, Pages 411-425
Molecular Aspects of Medicine

Review
Signalling and autophagy regulation in health, aging and disease

https://doi.org/10.1016/j.mam.2006.08.002Get rights and content

Abstract

It has become clear in recent years that autophagy not only serves to produce amino acids for ongoing protein synthesis and to produce substrates for energy production when cells become starved but autophagy is also able to eliminate defective cell structures and for this reason the process may be implicated in several diseased states. Autophagy is controlled by complex signalling pathways, including that used by insulin. In these pathways, phosphatidylinositol 3-kinases and the protein kinase mTOR play important roles.

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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