Epidemiological surveys suggest that the number of individuals aged 65 or older is expected to increase from 524 million in 2010 to nearly 1. 5 billion in 2050, worldwide. These geriatric individuals are at increased risk for developing chronic illness, and have reduced ability of regeneration of healthy tissue and endure whole organ transplantation procedures. Several age related changes in the liver include non-alcoholic fatty liver disease, alcoholic liver disease, hepatitis, fibrosis, and cirrhosis. Mounting evidence indicated that hepatic macrophages, a population comprised of both Kupffer cells and infiltrating monocyte derived macrophages, are involved in infiltration of liver during inflammation in various chronic liver diseases. Additionally, it is also known to play a crucial role in the homeostatic functions of the liver. However, mechanisms underlying age-related changes in the liver structure and cellular function, including hepatocytes and macrophages is not appropriately understood. Few researches conducted on macrophages taken from other aged sources, like the bone marrow, peritoneal cavity, lungs, and brain, showed decrease in autophagy and phagocytosis, dysfunction in cytokine signaling, and altered morphology and distribution, likely mediated by epigenetic changes and mitochondrial defects, associated with hepatic macrophages. 

It has reported by the current study that the decline in mitochondrial capacity with aging is the key mechanism related to changes seen in the function of both hepatocytes and macrophages, which in turn causes increased prevalence and severity of chronic liver diseases in elderly. The accumulation of infiltrating or M1-polarized monocytes/macrophages stimulates pathological changes causing liver diseases such as fibrosis, cirrhosis, and liver failure. 

Therefore, introduction of therapies targeting suppression of M1-polarization or infiltration of macrophages can reduce the progression of liver disease from initial stages to chronic end-stages requiring liver transplantation. Although, facilitating M2-gene expression, especially in older individuals might delay the progression of liver disease to advanced stages, it has been observed to cause tumor progression, including clinical hepatocellular carcinoma (HCC). Therefore, modulating macrophage polarization needs to be monitored carefully, so as to avoid both the appearance of liver fibrosis or HCC. Besides, managing the primary inducers of age-associated liver diseases such as alcohol consumption, visceral and ectopic fat accumulation, or deficits in mitochondrial capacity and other age-related mechanisms, is equally crucial as targeting the inflammatory symptoms to prevent these age-related liver diseases.

Source: Macrophages in the Aging Liver and Age-Related Liver Disease. Front Immunol. 2018;9:2795. Published 2018 Nov 30.