FASN activity is important for the initial stages of the induction of senescence
| Autor: | Ana O'Loghlen, Samuel James Davison Jordan, Juan Fafián-Labora, Maria Victoria Niklison-Chirou, Midusa Mahenthiran, Tamanna Shikh-Bahaei, Jose A. Rodriguez-Navarro, Sana Mohammad Abdullah, Paula Carpintero-Fernández |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Senescence Cancer Research Interleukin-1beta Immunology Apoptosis Article Small hairpin RNA Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Hepatic Stellate Cells medicine Animals Humans Secretion lcsh:QH573-671 Cellular Senescence biology Interleukin-6 Chemistry lcsh:Cytology TOR Serine-Threonine Kinases Cancer Cell Biology Fibroblasts medicine.disease Mitochondria Cell biology Fatty Acid Synthase Type I Mice Inbred C57BL Fatty acid synthase 030104 developmental biology Liver Ageing 030220 oncology & carcinogenesis Interleukin 1α Hepatic stellate cell biology.protein Female Tumor Suppressor Protein p53 Signal Transduction |
| Zdroj: | Cell Death and Disease, Vol 10, Iss 4, Pp 1-15 (2019) Cell Death & Disease |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/s41419-019-1550-0 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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