Metabolic dysfunction-associated steatohepatitis (MASH) follows a fatty liver, largely a consequence of obesity, but made worse by aging, in which fat-induced dysfunction of liver tissue maintenance leads to an increasing burden of fibrosis and loss of function. In fibrosis, the normal mechanisms of tissue maintenance run awry and excessive collagen is deposited to form scar-like structures that disrupt tissue function. At present fibrosis is largely irreversible, despite some potentially promising lines of research and development.
In recent years, aging and cellular senescence have triggered an increased interest in corresponding research fields. Evidence shows that the complex aging process is involved in the development of many chronic liver diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). In fact, aging has a tremendous effect on the liver, leading to a gradual decline in the metabolism, detoxification and immune functions of the liver, which in turn increases the risk of liver disease. These changes can be based on the aging of liver cells (hepatocytes, liver sinusoidal endothelial cells, hepatic stellate cells, and Kupffer cells). Similarly, patients with liver diseases exhibit increases in the aging phenotype and aging cells, often manifesting as faster physical functional decline, which is closely related to the promoting effect of liver disease on aging.
In conclusion, there is a close bidirectional relationship between MASLD/MASH and aging. After aging, the prevalence, severity, and mortality of MASLD/MASH all increase. At the same time, MASLD/MASH can exacerbate liver aging, leading to the senescence of liver cells and affecting the normal functions of the liver. However, the detailed mechanisms by which aging contributes to the development of MASLD/MASH and why aging is exacerbated by this disease remain unclear. Moreover, the causal relationship between the two is not explained in detail, which one comes first and which one comes next. Future studies should further explore the specific mechanisms of this relationship and develop targeted preventive and therapeutic strategies to mitigate the impact of liver disease on the aging process and delay the progression of liver disease in the elderly population.
Link: https://doi.org/10.1007/s11684-025-1133-7
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