Aspirin Recapitulates Features of Caloric Restriction

Federico Pietrocola, Francesca Castoldi, Maria Markaki, Sylvie Lachkar, Guo Chen, David P. Enot, Sylvere Durand, Noelie Bossut, Mingming Tong, Shoaib A. Malik, Friedemann Loos, Nicolas Dupont, Guillermo Mariño, Nejma Abdelkader, Frank Madeo, Maria Chiara Maiuri, Romano Kroemer, Patrice Codogno, Junichi Sadoshima, Nektarios TavernarakisGuido Kroemer

Research output: Contribution to journalArticlepeer-review

85 Scopus citations


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fails to further increase autophagy levels in EP300-deficient cells, as well as in cells in which endogenous EP300 has been replaced by salicylate-resistant EP300 mutants.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. Pietrocola et al. show that the inhibition of the acetyltransferase EP300 is determinant for the autophagy-inducing effect of aspirin and its active metabolite salicylate. As a proof of the evolutionarily conserved nature of this mechanism, the authors demonstrate that aspirin triggers protective autophagy in mice and in the nematode C. elegans.

Original languageEnglish (US)
Pages (from-to)2395-2407
Number of pages13
JournalCell Reports
Issue number9
StatePublished - Feb 27 2018

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)


  • EP300
  • acetylation
  • aging
  • autophagy
  • longevity
  • metabolome
  • salicylate


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