Aging of Liver in Its Different Diseases

Abstract

The proportion of elderly people in the world population is constantly increasing. With age, the risk of numerous chronic diseases and their complications also rises. Research on the subject of cellular senescence date back to the middle of the last century, and today we know that senescent cells have different morphology, metabolism, phenotypes and many other characteristics. Their main feature is the development of senescence-associated secretory phenotype (SASP), whose pro-inflammatory components affect tissues and organs, and increases the possibility of age-related diseases. The liver is the main metabolic organ of our body, and the results of previous research indicate that its regenerative capacity is greater and that it ages more slowly compared to other organs. With age, liver cells change under the influence of various stressors and the risk of developing chronic liver diseases such as non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcoholic steatohepatitis (ASH) and hepatocellular carcinoma (HCC) increases. It has been proven that these diseases progress faster in the elderly population and in some cases lead to end-stage liver disease that requires transplantation. The treatment of elderly people with chronic liver diseases is a challenge and requires an individual approach as well as new research that will reveal other safe and effective therapeutic modalities.

Keywords: DDR; SASP; cell; elderly; inflammaging; liver; senescence.

Figure 1

From senescence to age-related diseases. Senescence through components of senescence-associated secretory fenotype (SASP) causes inflammation in tissues and organs which in the end results in occurrence of age-related diseases.

Figure 2

The components of SASP are numerous, but the most important ones are: interleukin (IL) 6, 8 and 1, tumor necrosis factor alpha (TNF-α), transforming growth beta (TGF), vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs), protein CCN1 and fibronectin1 (FN1).

Figure 3

The bystander effect: senescent cells are more secretory active than non-senescent cells and paracrine can affect young cells and induce the start of the senescence process in them. This is accomplished through proinflammatory cytokines and reactive oxygen species (ROS) which cause deoxyribonucleic acid (DNA) damage and initiate DNA damage response (DDR). In this way, the normal cell enters in permanent cycle arrest or senescence. Hallmark of senescence is defined by Gorgoulis et al. [26].

Figure 4

Roles of the liver.