Macrophages in the Aging Liver and Age-Related Liver Disease

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.

Regulation of lipid‐induced macrophage polarization through modulating peroxisome proliferator‐activated receptor‐gamma activity affects hepatic lipid metabolism via a Toll‐like receptor 4/NF‐κB signaling pathway

“…Hepatic macrophages exert a crucial role in the pathogenesis of various chronic liver diseases 7–9 . As resident macrophages in the liver, Kupffer cells can undergo a wide range of phenotypic and functional switching depending on the environmental stimuli they receive.…”

Liver Macrophages: Old Dogmas and New Insights

“…As a consequence, numerous reviews are available on the crucial roles of hepatic macrophages in liver cancer, (7)(8)(9) fibrosis, (6,10,11) alcoholic liver disease and bacterial infections, (12)(13)(14)(15)(16) nonalcoholic fatty liver disease, (17)(18)(19) viral hepatitis, (20) cholestatic diseases, (21,22) drug-induced acute liver injury, (23,24) ischemia reperfusion injury and liver transplant, (25,26) liver regeneration, (23,27,28) and also in aging liver. (29) Because our knowledge on macrophages in the context of liver disease has increased exponentially over recent years, a fresh view on this fascinating immune cell population has emerged, challenging some old dogmas and highlighting the heterogeneity and plasticity of liver macrophages.…”

Improvement of cognitive and motor performance with mitotherapy in aged mice

“…Besides cognitive and motor performance, ATP-dependent immune responses of macrophages reduce in aged animals [15,16], which are particularly at risk for developing chronic diseases. We have identified that exogenous mitochondria are not able to enter red blood cells because the cells lack endocytic function [ 17 ].…”