Age-related M1/M2 phenotype changes in circulating monocytes from healthy/unhealthy individuals

Macrophage polarization is a candidate biomarker of disease-related inflammatory status, but its modulation during aging has not been investigated. To do this, the M1/M2 profile was assessed by CD80/CD163 gating in classical (CD14 ++ CD16 - ), intermediate (CD14 ++ CD16 + ), and non-classical (CD14 low CD16 + ) monocytes from 31 healthy subjects (CTRs) of different ages. Cytofluorimetric analysis showed a significantly different CD80/CD163 distribution in the three subsets, as more than 80% of classical and intermediate monocytes were CD80 + CD163 + , whereas most non-classical monocytes were CD80 - CD163 - and CD163 + . Non-classical CD163 + monocytes were significantly higher whereas classical CD163 + and CD80 - CD163 - monocytes significantly lower in older than younger CTRs (cut-off, 65 years), suggesting different age-related trends for M2 subsets. To establish whether an M1/M2 imbalance could be associated with disease, 21 patients with acute myocardial infarction (AMI) were compared with older CTRs. The AMI patients showed a significantly decreased proportion of CD163 + CD80 + and an increased proportion of CD163 + and CD163 - CD80 - cells among classical monocytes, opposite trends to those observed in healthy aging. Moreover, a significantly greater proportion of intermediate and non-classical CD80 + monocytes suggested a shift to a pro-inflammatory phenotype. Overall, CD163/CD80 cytofluorimetric characterization of circulating monocytes provides additional information about their polarization and could be an innovative tool to monitor aging.