Macrophages Show Different Aging Patterns Across Body Tissues

Macrophages function as the body’s cleanup and maintenance crew, found in nearly every tissue where they fight infections, remove damaged cells, repair tissues, and control inflammation. However, these critical immune cells change as the body ages, contributing to reduced immune effectiveness over time. A new study published in BMC Biology examines how macrophages age across different tissues to better understand why immune function declines with age.

USC researchers analyzed macrophage data from multiple mouse tissues, including the brain, lungs, liver, and other organs, comparing younger and older animals. The work revealed both universal aging patterns shared across many macrophage populations and important tissue-specific differences. “We know that aging affects immune cells like macrophages, but most studies focus on a single tissue or organ, so there is little known on how local tissue environment can impact immune cell aging,” said Bérénice Benayoun, the study’s senior author. The team sought to determine whether immune cells age uniformly throughout the body or whether each tissue follows its own aging trajectory.

The findings showed both patterns occur. Aging macrophages across tissues become increasingly focused on responding to stress and cellular damage while appearing to lose molecular programs involved in maintaining healthy tissue structure and communication. Yet macrophages in different organs age distinctly. Brain macrophages showed different age-related changes than lung macrophages, for example. Additionally, aging affected macrophages differently in males and females across tissues.

Despite these variations, the study identified a set of genes and molecular pathways that changed consistently across many macrophage types. These consistent changes could represent core features of immune aging and potential targets for future treatments. The researchers note that understanding these patterns is urgent, as age-related immune dysfunction contributes to chronic inflammation, increased infection susceptibility, impaired wound healing, and diseases associated with aging.

First author Ella Schwab emphasized the value of their approach: “There’s an incredible wealth of publicly available, underutilized sequencing data for studying immune aging. By analyzing data from dozens of pre-existing studies, we could examine how macrophages age across tissues and between sexes—something no single study had the power to do alone.” 

The findings suggest future therapeutic approaches may need to account for both the tissue involved and biological sex rather than applying one-size-fits-all solutions. By creating a comprehensive map of macrophage aging across the body, researchers hope to provide a valuable resource for developing strategies to maintain immune health in aging populations.