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Medicine: Flushing out cells alleviates fatty liver disease

Nature Communications

June 14, 2017

A new therapy to treat fatty liver disease, based on the elimination of ‘old’ (so-called senescent) liver cells, is demonstrated in mice in Nature Communications this week. The study finds that senescent liver cells promote the accumulation of fat in the liver and shows that drugs that selectively kill senescent cells can reduce liver disease in mice.

The risk of developing non-alcoholic fatty liver disease - a condition characterised by the build-up of fat in the liver that can lead to liver inflammation, cirrhosis and cancer - increases with age but it is unclear why. It has been suggested that the accumulation of senescent cells, which increase in response to stresses (such as DNA damage) and as the body ages, might contribute to the decline of tissues and organ function in old humans. Senescent cells essentially shut down most of their typical cellular functions and can alter the function of neighbouring cells by releasing signalling molecules.

Diana Jurk and colleagues show that senescent liver cells cannot break down fat cells as efficiently as normal liver cells, which promotes fat accumulation in the liver of mice. Increasing the number of senescent cells in the mouse liver by inducing DNA damage worsens symptoms of fatty liver disease. Conversely, administration of a combination of two drugs known to selectively kill senescent cells (dasatinib and quercetin), reduces fatty liver disease in mice.

The study increases our understanding of how senescent cells contribute to ageing-associated diseases and suggests that strategies aimed at killing senescent cells might be beneficial in patients with non-alcoholic fatty liver disease.

doi: 10.1038/ncomms15691

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