Non-alcoholic fatty liver disease (NAFLD) is an excess of lipids in the liver, disruptive of liver function. In our modern society of cheap calories and machineries of comfort the most common way to achieve an excess of lipids in the liver is obesity. That perhaps obscures the point that aspects of aging, such as growing mitochondrial dysfunction, change liver metabolism, and metabolism in general, to increase the risk of suffering NAFLD at a given weight in later life. We might not tend to think of NAFLD as an age-related condition per se, but it is certainly influenced by aging.
Due to the decline in the regenerative ability of the liver and dysfunctions in the immune response, older people are more likely to suffer from non-alcoholic fatty liver disease (NAFLD), acute and chronic liver injury, liver fibrosis, and other diseases. Studies have reported that the prevalence of NAFLD increases in the elderly, with a prevalence of less than 30% in people under 40 years of age and more than 50% in people over 60 years of age.
Currently, it is believed that the mechanism of development of NAFLD includes increased production of fat, increased dietary free fatty acid (FFA) levels, β-oxidative damage, and dysfunction in very low density lipoprotein synthesis. However, reduced activity and changes in diet structure lead to a continuous increase in body fat in the elderly. These factors lead to the accumulation of triglycerides (TGs) in the liver and eventually cause age-related NAFLD.
Studies have reported that the accumulation of TG droplets in hepatocytes is not a harmful process in itself. On the contrary, it is considered an adaptive response to excessive lipid uptake or the production of fat, and this imbalance in TG synthesis and breakdown causes fatty degeneration of the liver. In addition, the structural and functional changes in the mitochondria have been shown to be related to the pathogenesis of NAFLD. Ultramicroscopic analyses have demonstrated a disordered morphology of hepatocyte mitochondria in elderly patients with NAFLD, and the damage to the structure and function led to fatty degeneration of the liver and other injuries.
The changes in mitosis and fusion of mitochondria during ageing lead to the inhibition of mitochondrial phagocytosis. Cell function can be affected further if the damaged mitochondria are not cleared in time. The structural and functional changes in the mitochondria have been proven to be related to the pathogenesis of NAFLD, the loss of mitochondrial DNA (mtDNA) in hepatocytes affects function, leading to hepatic steatosis and other injuries. The present study reviewed the manifestations, role and mechanism of mitochondrial dysfunction in the progression of NAFLD in the elderly. In addition, the study discusses the treatment strategies for NAFLD based on the understanding of mitochondrial dysfunction and abnormal lipid metabolism to provide new ideas for the development of innovative drugs for the prevention and treatment of NAFLD.