Old age and steatohepatitis: A dangerous liaison?


  • Manlio Vinciguerra PhD

    1. University College London (UCL), Institute for Liver and Digestive Health, Division of Medicine, Royal Free Campus, London, UK
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  • Potential conflict of interest: Nothing to report.

To The Editor:

I read with great interest the article by Fontana et al.[1] in which the authors demonstrate in mice that aging does not favor or worsen the accumulation of intrahepatic lipids, whereas it promotes hepatocellular injury and inflammation (nonalcoholic steatohepatitis [NASH]), due to the activation of the Fas death pathway and M1 macrophage polarization. The authors used naïve mice aged 2, 8, and 18 months, reflecting young, middle, and old age, and fed them a high fat diet (HFD). Whereas increased body weight and features of the metabolic syndrome were observed in all the groups, liver injury occurred only in the two older age groups as detected by transaminase levels and apoptosis assays. Therefore, aging affected inflammation and injury in the liver induced by HFD, but not insulin sensitivity.[1] Although these findings are in line with the inflamm-aging theory, according to which aging accrues liver inflammation,[2] and show that aging per se does not affect steatosis, there are some interesting aspects to be underlined. Steatosis/NASH are common precursors of hepatocellular carcinoma (HCC), and the aging liver has been shown in rodents to provide a pro-proliferative clonogenic environment.[3] However, very strong epidemiological data suggest that in humans the incidence of HCC drops significantly in individuals aged more than 70.[4] Interestingly, there are only inconclusive data available on the progression from steatosis to NASH in the very elderly.[5] Mice aged of 18 months, like the ones used in this study, correspond to humans age 56, roughly.[6] Fontana et al. do not address the relationship between very old age and steatosis/NASH. There might be an age window when the livers of “survivors” (mouse or human) become resistant to develop injury, which needs to be looked at to understand fully the interaction between age and liver diseases in a therapeutic perspective.

  • Manlio Vinciguerra PhD

  • Head of Epigenetics of Fatty Liver Diseases Unit, Institute of Hepatology, Harold Samuel House, London, UK