Chronic Inflammation and Macrophage Dysfunction in Aging

Chronic inflammation is of great importance in degenerative aging. Unresolved inflammation that lingers for the long term disrupts tissue function and accelerates the onset and progression of many age-related conditions. There is thus considerable interest in the research community in finding ways to shut down chronic inflammation in older individuals without suppressing beneficial, necessary short-term inflammatory signaling, involved in defense against pathogens, tissue regeneration, and other processes. Macrophages are innate immune cells that have many important functions and are negatively affected by an environment of chronic inflammation. Equally, it appears that they contribute to producing that environment via their inflammatory signals, in cases where they become overactive due to a damaged environment or due to spreading cellular senescence.

Older age is associated with deteriorating health, including escalating risk of diseases such as cancer, and a diminished ability to repair following injury. This rise in age-related diseases/co-morbidities is associated with changes to immune function, including in myeloid cells, and is related to immunosenescence. Immunosenescence reflects age-related changes associated with immune dysfunction and is accompanied by low-grade chronic inflammation or inflammageing. This is characterised by increased levels of circulating pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-1β and IL-6.

However, in healthy ageing, there is a concomitant age-related escalation in anti-inflammatory cytokines such as transforming growth factor-β1 (TGF-β1) and IL-10, which may overcompensate to regulate the pro-inflammatory state. Key inflammatory cells, macrophages, play a role in cancer development and injury repair in young hosts, and we propose that their role in ageing in these scenarios may be more profound. Imbalanced pro- and anti-inflammatory factors during ageing may also have a significant influence on macrophage function and further impact the severity of age-related diseases in which macrophages are known to play a key role.

In this brief review we summarise studies describing changes to inflammatory function of macrophages (from various tissues and across sexes) during healthy ageing. We also describe age-related diseases and co-morbidities where macrophages are known to play a key role, focused on injury repair processes and cancer, plus comment briefly on strategies to correct for these age-related changes.


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