As we get older, a type of tissue called brown adipose tissue (BAT) becomes less active in generating heat. We don't fully understand why this happens, but we have discovered that certain immune cells from the bone marrow, specifically T cells and neutrophils, invade the BAT of older male rats and mice. These immune cells, along with fat cells and nerves, disrupt the networks of nerve fibers in the BAT. This disruption is caused by the immune cells releasing a protein called S100A8, which inhibits the expression of a protein called RNA-binding motif protein 3. This disruption affects the genes responsible for guiding the nerve fibers, leading to impaired nerve connections and reduced heat production. We have also found that human immune cells with S100A8 can infiltrate the BAT of mice and cause similar problems. However, when we treated the mice with an inhibitor of S100A8 called paquinimod, the nerve networks and heat production in the BAT improved in older mice. This suggests that targeting these aging immune cells could be a way to improve the functioning of BAT and related metabolic disorders in older individuals.
Introduction:
When we activate a certain type of tissue called brown adipose tissue (BAT), it helps us produce heat and has positive effects on our metabolism. However, as we get older, BAT becomes less active, leading to increased fat, inflammation, and reduced heat production. We know that aging affects our immune system, but we don't fully understand how aging immune cells contribute to the decline of BAT. The nervous system also plays a role in BAT function, and recent studies have shown that interactions between nerves and immune cells are important for the functioning of fat tissue. However, we still don't know how nerves and immune cells work together in BAT, especially in older individuals who have impaired nerve connections. One protein of interest is S100A8, which is involved in inflammation and has been found to increase in aging tissues, including BAT. In this study, we looked at a group of aging immune cells that produce S100A8 and found that they accumulate in the BAT of older mice, contributing to BAT aging. These immune cells, along with nerves and fat cells, disrupt the nerve connections in BAT. Importantly, we found that when we used an inhibitor called paquinimod to reduce S100A8 in BAT, it improved the metabolic problems associated with obesity in older mice.
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