FASN activity is important for the initial stages of the induction of senescence

Juan Fafián-Labora, Paula Carpintero-Fernández, Samuel James Davison Jordan, Tamanna Shikh-Bahaei, Sana Mohammad Abdullah, Midusa Mahenthiran, José Antonio Rodríguez-Navarro, Maria Victoria Niklison-Chirou, Ana O’Loghlen

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6 Citations (Scopus)

Abstract

Senescent cells accumulate in several tissues during ageing and contribute to several pathological processes such as ageing and cancer. Senescence induction is a complex process not well defined yet and is characterized by a series of molecular changes acquired after an initial growth arrest. We found that fatty acid synthase (FASN) levels increase during the induction of senescence in mouse hepatic stellate cells and human primary fibroblasts. Importantly, we also observed a significant increase in FASN levels during ageing in mouse liver tissues. To probe the central role of FASN in senescence induction, we used a small-molecule inhibitor of FASN activity, C75. We found that C75 treatment prevented the induction of senescence in mouse and human senescent cells. Importantly, C75 also reduced the expression of the signature SASP factors interleukin 1α (IL-1α), IL-1β and IL-6, and suppressed the secretion of small extracellular vesicles. These findings were confirmed using a shRNA targeting FASN. In addition, we find that FASN inhibition induces metabolic changes in senescent cells. Our work underscores the importance of C75 as a pharmacological inhibitor for reducing the impact of senescent cell accumulation.

Original languageEnglish
Article number318
JournalCell Death and Disease
Volume10
Issue number4
DOIs
Publication statusPublished - 1 Apr 2019

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Cite this

Fafián-Labora, J., Carpintero-Fernández, P., Jordan, S. J. D., Shikh-Bahaei, T., Abdullah, S. M., Mahenthiran, M., Rodríguez-Navarro, J. A., Niklison-Chirou, M. V., & O’Loghlen, A. (2019). FASN activity is important for the initial stages of the induction of senescence. Cell Death and Disease, 10(4), [318]. https://doi.org/10.1038/s41419-019-1550-0