Macrophages are cells of the innate immune system, found throughout the body, and which play a great many roles beyond the obvious ones of defending against invading pathogens. They destroy cancerous and senescent cells, ingest molecular waste and debris between cells, and participate in the processes of tissue regeneration and maintenance, to pick a few examples. Further, the immune system of the brain includes an analogous population of cells known as microglia, which additionally take on supporting roles essential to the proper functioning of neurons and their synaptic connections.

Chronic inflammation is important in the progression of age-related diseases, and as a part of the immune system macrophages are very much involved in inflammation. This is a two-way street; greater inflammatory signaling in the environment will tend to make macrophages adopt a more aggressive behavior, adding their own inflammatory signaling to the mix. Equally, macrophages that become inflammatory for other reasons can rouse greater and broader inflammation via their actions. This is particularly true for senescent microglia, which appear quite important in a number of age-related conditions.

Setting aside cellular senescence, macrophage behavior can be loosely divided into phenotypes known as polarizations. M1 macrophages are inflammatory and focused on attacking pathogens, while M2 macrophages are anti-inflammatory and focused on regeneration. This is a useful categorization, while recognizing that it perhaps oversimplifies the reality of a continuous distribution of behaviors, not a pair of widely separate states. Some aspects of aging are associated with a shift in populations to favor M1 over M2, but this is not universal. Nonetheless, a number of research groups are working to find ways to bias macrophages to one polarization over another, to turn their contribution from harmful to helpful.

Targeting Macrophages: Friends or Foes in Disease?