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.