Ageing, telomeres, senescence, and liver injury.
Populations in developed countries continue to grow older and an understanding of the ageing process to allow healthy ageing carries important medical implications. Older individuals are more susceptible to most acquired liver disorders and more vulnerable to the consequences of liver disease. Accordingly, age is a critical determinant of outcome for hepatitis C virus infection and liver transplantation. In this review we describe changes in the ageing liver and discuss mechanisms of senescence at the cellular level. In particular, we focus on mechanisms by which inflammation, oxidative stress, and oncogenic stress accelerate cellular senescence. In the setting of chronic hepatic injury and inflammation, cellular senescence functions as an essential stress-response mechanism to limit the proliferation of damaged cells and reduce the risk of malignancy, but this benefit is achieved at the expense of senescence-related organ dysfunction. The dual role of cell senescence in chronic liver disease will make this an intriguing but challenging area for future clinical interventions.
Hoare
Matthew
M
Department of Medicine, University of Cambridge, Cambridge, UK.
Das
Tapas
T
Alexander
Graeme
G
D000375:Aging; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics; D016922:Cellular Senescence; D002908:Chronic Disease; D004249:DNA Damage; D022781:Hepatocytes / Q000473:pathology; D006801:Humans; D008107:Liver Diseases / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics; D018384:Oxidative Stress; D015398:Signal Transduction; D016615:Telomere; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D016159:Tumor Suppressor Protein p53