The age-associated deterioration in cellular and organismal functions associates with dysregulation of nutrient-sensing pathways and disabled autophagy. The reactivation of autophagic flux may prevent or ameliorate age-related metabolic dysfunctions. Non-toxic compounds endowed with the capacity to reduce the overall levels of protein acetylation and to induce autophagy have been categorized as caloric restriction mimetics (CRMs). Here, we show that aspirin or its active metabolite salicylate induce autophagy by virtue of their capacity to inhibit the acetyltransferase activity of EP300. While salicylate readily stimulates autophagic flux in control cells, it fails to further increase autophagy levels in EP300-deficient cells, as well as in cells in which endogenous EP300 has been replaced by salicylate-resistant EP300 mutants. Accordingly, the pro-autophagic activity of aspirin and salicylate on the nematode Caenorhabditis elegans is lost when the expression of the EP300 ortholog cpb-1 is reduced. Altogether, these findings identify aspirin as an evolutionary conserved CRM.

Departamento de Biología Fundamental Universidad de Oviedo Fundación para la Investigación Sanitaria del Principado de Asturias Oviedo Spain

Department of Cell Biology and Molecular Medicine Rutgers New Jersey Medical School Newark NJ USA

Gustave Roussy Cancer Campus Villejuif France; INSERM U1138 Paris France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer Centre de Recherche des Cordeliers Paris France; Université Paris Descartes Paris 5 Sorbonne Paris Cité Paris France; Metabolomics and Cell Biology Platforms Gustave Roussy Cancer Campus Villejuif France; Université Pierre et Marie Curie Paris France

Gustave Roussy Cancer Campus Villejuif France; INSERM U1138 Paris France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer Centre de Recherche des Cordeliers Paris France; Université Paris Descartes Paris 5 Sorbonne Paris Cité Paris France; Metabolomics and Cell Biology Platforms Gustave Roussy Cancer Campus Villejuif France; Université Pierre et Marie Curie Paris France; Department of Biochemistry Sargodha Medical College Sargodha Pakistan

Gustave Roussy Cancer Campus Villejuif France; INSERM U1138 Paris France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer Centre de Recherche des Cordeliers Paris France; Université Paris Descartes Paris 5 Sorbonne Paris Cité Paris France; Metabolomics and Cell Biology Platforms Gustave Roussy Cancer Campus Villejuif France; Université Pierre et Marie Curie Paris France; Pôle de Biologie Hôpital Européen Georges Pompidou AP HP Paris France; Karolinska Institute Department of Women's and Children's Health Karolinska University Hospital Stockholm Sweden

Gustave Roussy Cancer Campus Villejuif France; INSERM U1138 Paris France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer Centre de Recherche des Cordeliers Paris France; Université Paris Descartes Paris 5 Sorbonne Paris Cité Paris France; Metabolomics and Cell Biology Platforms Gustave Roussy Cancer Campus Villejuif France; Université Pierre et Marie Curie Paris France; Université Paris Sud Paris XI Faculté de Médecine Kremlin Bicêtre France Paris France; Sotio a c Prague Czech Republic

Institute of Molecular Biology and Biotechnology Foundation for Research and Technology Hellas Heraklion 70013 Crete Greece

Institute of Molecular Biology and Biotechnology Foundation for Research and Technology Hellas Heraklion 70013 Crete Greece; Department of Basic Sciences Faculty of Medicine University of Crete Heraklion 70013 Crete Greece

Institute of Molecular Biosciences NAWI Graz University of Graz Humboldtstraße 50 8010 Graz Austria; BioTechMed Graz Humboldtstraße 50 8010 Graz Austria

Metabolomics and Cell Biology Platforms Gustave Roussy Cancer Campus Villejuif France

Scientific Computing LGCR Sanofi R and D 94403 Vitry sur Seine France

Structure Design and Informatics LGCR Sanofi R and D 94403 Vitry sur Seine France

Université Paris Descartes Paris 5 Sorbonne Paris Cité Paris France; Institut Necker Enfants Malades Paris France; INSERM U1151 Paris France; CNRS UMR8253 Paris France

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Autophagy. 2018;14(7):1162-1163. doi: 10.1080/15548627.2018.1454810. PubMed

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