Abstract
The number of individuals aged 65 or older is projected to increase globally from 524 million in 2010 to nearly 1. 5 billion in 2050. Aged individuals are particularly at risk for developing chronic illness, while being less able to regenerate healthy tissue and tolerate whole organ transplantation procedures. In the liver, these age-related diseases include non-alcoholic fatty liver disease, alcoholic liver disease, hepatitis, fibrosis, and cirrhosis. Hepatic macrophages, a population comprised of both Kupffer cells and infiltrating monocyte derived macrophages, are implicated in several chronic liver diseases and also play important roles in the homeostatic functions of the liver. The effects of aging on hepatic macrophage population dynamics, polarization, and function are not well understood. Studies performed on macrophages derived from other aged sources, such as the bone marrow, peritoneal cavity, lungs, and brain, demonstrate general reductions in autophagy and phagocytosis, dysfunction in cytokine signaling, and altered morphology and distribution, likely mediated by epigenetic changes and mitochondrial defects, that may be applicable to hepatic macrophages. This review highlights recent findings in macrophage developmental biology and function, particularly in the liver, and discusses the role of macrophages in various age-related liver diseases. A better understanding of the biology of aging that influences hepatic macrophages and thus the progression of chronic liver disease will be crucial in order to develop new interventions and treatments for liver disease in aging populations.
Highlights
TO MACROPHAGES IN THE LIVERThe liver is an important immunological organ, serving as a surveillance system for gut-derived pathogens and producing several key immune components—complement, acute phase, and coagulation proteins [1, 2]
As most of the experimental data has been collected from murine animal models, this review focuses largely on preclinical studies in mice and extends these findings to chronic liver disease in humans
Both Kupffer cells and infiltrating monocytes are implicated to various levels in the etiology of chronic liver disease, the distinction between these two cell populations is less clear in human clinical liver samples compared to animal studies
Summary
Aged individuals are at risk for developing chronic illness, while being less able to regenerate healthy tissue and tolerate whole organ transplantation procedures. In the liver, these age-related diseases include non-alcoholic fatty liver disease, alcoholic liver disease, hepatitis, fibrosis, and cirrhosis. A population comprised of both Kupffer cells and infiltrating monocyte derived macrophages, are implicated in several chronic liver diseases and play important roles in the homeostatic functions of the liver. This review highlights recent findings in macrophage developmental biology and function, in the liver, and discusses the role of macrophages in various age-related liver diseases.
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