Senescence in chronic liver disease: Is the future in aging?

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• 作者：Aloysious D. Aravinthan¹ ; ⁴ ; Graeme J.M. Alexander² ; ³ ; ^{gja1000@doctors.org.uk" class="auth_mail" title="E-mail the corresponding author}
• 关键词：mTORC1 ; mammalian target of rapamycin complex 1 ; SADF ; senescence-associated DNA damage foci ; SAHF ; senescence-associated heterochromatic foci ; SASP ; senescence-associated secretory phenotype ; SA-β-GAL ; senescence-associated β-galactosidase
• 刊名：Journal of Hepatology
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：65
• 期：4
• 页码：825-834
• 全文大小：1575 K

文摘

Cellular senescence is a fundamental, complex mechanism with an important protective role present from embryogenesis to late life across all species. It limits the proliferative potential of damaged cells thus protecting against malignant change, but at the expense of substantial alterations to the microenvironment and tissue homeostasis, driving inflammation, fibrosis and paradoxically, malignant disease if the process is sustained. Cellular senescence has attracted considerable recent interest with recognition of pathways linking aging, malignancy and insulin resistance and the current focus on therapeutic interventions to extend health-span. There are major implications for hepatology in the field of fibrosis and cancer, where cellular senescence of hepatocytes, cholangiocytes, stellate cells and immune cells has been implicated in chronic liver disease progression. This review focuses on cellular senescence in chronic liver disease and explores therapeutic opportunities.