A recent study published in the Computational and Structural Biotechnology Journal reported that while the liver demonstrates remarkable resilience during aging, there is growing evidence that it undergoes all the cellular hallmarks of aging, which increases the risk of liver and systemic disease.

The authors stated that the aging process in the liver is driven by alterations of genome and epigenome that contribute to dysregulation of mitochondrial function and nutrient sensing pathways, leading to cellular senescence and low-grade inflammation. These changes promote multiple phenotypic changes in all liver cells – hepatocytes, liver sinusoidal endothelial, hepatic stellate and Küpffer cells, and impairment of hepatic function. Specifically, age-related changes in the liver sinusoidal endothelial cells are a significant but under-recognized risk factor for the development of age-related cardiometabolic disease.

This article elaborated that the aging process in the liver is promoted by alterations in the genome and epigenome that contribute to dysregulation of mitochondrial function and nutrient sensing pathways. This leads to cellular senescence and low-grade inflammation facilitating multiple phenotypic changes in all liver cells – hepatocytes, liver sinusoidal endothelial, hepatic stellate and Küpffer cells. The interconnectome between these pathways has been shown by the recent applications of -omics studies to investigate age-related changes that occur in the liver. In 1985 one of the founding fathers of hepatology, Hans Popper (Sem Liver Disease) made the prescient statement that “the effect of age on the liver and of the liver on aging is full of promise if available methodologies are rigorously applied”. Since that time there has been a dramatic increase in technologies, particularly the various -omics, that have profoundly influenced the understanding of the aging liver.

Of the cells of the liver, liver sinusoidal endothelial cells (LSECs) are a significant but under-recognized risk factor for development of age-related cardiometabolic disease. These cells are drastically changed during aging, but may also act as a therapeutic target for age-related cardiometabolic diseases.

Source: Computational and Structural Biotechnology Journal. 2019;17:1151-1161. doi:10.1016/j.csbj.2019.07.021