{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T23:00:13Z","timestamp":1778799613801,"version":"3.51.4"},"reference-count":199,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,16]],"date-time":"2021-10-16T00:00:00Z","timestamp":1634342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Autophagy is a \u201chousekeeping\u201d lysosomal degradation process involved in numerous physiological and pathological processes in all eukaryotic cells. The dysregulation of hepatic autophagy has been described in several conditions, from obesity to diabetes and cholestatic disease. We review the role of autophagy, focusing on age-related cholestatic diseases, and discuss its therapeutic potential and the molecular targets identified to date. The accumulation of toxic BAs is the main cause of cell damage in cholestasis patients. BAs and their receptor, FXR, have been implicated in the regulation of hepatic autophagy. The mechanisms by which cholestasis induces liver damage include mitochondrial dysfunction, oxidative stress and ER stress, which lead to cell death and ultimately to liver fibrosis as a compensatory mechanism to reduce the damage. The stimulation of autophagy seems to ameliorate the liver damage. Autophagic activity decreases with age in several species, whereas its basic extends lifespan in animals, suggesting that it is one of the convergent mechanisms of several longevity pathways. No strategies aimed at inducing autophagy have yet been tested in cholestasis patients. However, its stimulation can be viewed as a novel therapeutic strategy that may reduce ageing-dependent liver deterioration and also mitigate hepatic steatosis.<\/jats:p>","DOI":"10.3390\/cells10102772","type":"journal-article","created":{"date-parts":[[2021,10,17]],"date-time":"2021-10-17T23:13:32Z","timestamp":1634512412000},"page":"2772","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Involvement of Autophagy in Ageing and Chronic Cholestatic Diseases"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8585-9495","authenticated-orcid":false,"given":"Claudio","family":"Pinto","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabetta","family":"Ninfole","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Benedetti","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Marzioni","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Maroni","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1083\/jcb.119.2.301","article-title":"Autophagy in Yeast Demonstrated with Proteinase-Deficient Mutants and Conditions for Its Induction","volume":"119","author":"Takeshige","year":"1992","journal-title":"J. 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