Metformin: a metabolic modulator

// Federico Pietrocola 1,2,3,4,5,6 and Guido Kroemer 1,2,3,4,5,6,7,8 1 Gustave Roussy Comprehensive Cancer Institute, Villejuif, France 2 INSERM, U1138, Paris, France 3 Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France 4 Université Paris Descartes/Paris V, Sorbonne Paris Cité, Paris, France 5 Université Pierre et Marie Curie/Paris VI, Paris, France 6 Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France 7 Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France 8 Department of Women’s and Children’s Health, Karolinska University Hospital, Stockholm, Sweden Correspondence to: Guido Kroemer, email: // Keywords : aging, autophagy, biguanides, caloric restriction, cancer Received : January 06, 2017 Accepted : January 12, 2017 Published : January 22, 2017 Abstract Recent findings have shed new light on the mechanisms of action through which biguanides exert their anti-aging and cytostatic effects in Caenorhabditis elegans and human cell lines. The drop in energy charge resulting from the metformin mediated inhibition of mitochondrial activity affects the function of the nuclear pore complex, blocks mTOR signaling and enhances the expression of ACAD10. Whether the inhibition of this pathway is truly responsible for the anti-diabetic and cancer effects of the drug in mammals remains to be established.