Accumulating data are documenting an inverse relationship between immune status, response to vaccination, health, and longevity, suggesting that the immune system becomes less effective with advancing age and that this is clinically relevant. The mechanisms and consequences of age-associated immune alterations, designated immunosenescence, are briefly reviewed here.

Regular exercise may improve systemic markers of chronic inflammation, but direct evidence and dose-response information is lacking. The objective of this study was to examine the effect and time course of changes in markers of chronic inflammation in response to progressive exercise training (and subsequent detraining). Forty-one sedentary men 45-64 yr of age completed either a progressive 24-wk exercise intervention or control followed by short-term removal of the intervention (2-wk detraining). Serum IL-6 fell by -0.4 pg/ml (SD 0.6) after 12 wk and responded to moderate-intensity exercise. Serum alanine aminotransferase (ALT) activity fell -7 U/l (SD 11) at 24 wk although there was no evidence of any change by week 12 (and therefore ALT required more vigorous-intensity activity and/or a more prolonged intervention). The effect on IL-6 was lost after 2-wk detraining whereas the change in ALT was retained. The temporal fall and rise in IL-6 with training and subsequent detraining in men with high IL-6 at baseline provided a retrospective opportunity to examine parallel genomic changes in peripheral mononuclear cells. A subset of 53 probes was differentially regulated by at least twofold after training with 31 of these changes being lost after detraining (n = 6). IL-6 responded quickly to the carefully monitored exercise intervention (within weeks) and required only moderate-intensity exercise, whereas ALT took longer to change and/or required more vigorous-intensity exercise. Further work is required to determine whether any of the genes that temporally changed in parallel with changes in IL-6 are a cause or consequence of this response.

White adipose tissue exhibits inflammation as tissue mass expands in obesity, involving macrophage infiltration and a direct inflammatory response by adipocytes. DNA microarrays and conditioned medium have been used to examine the effects of macrophages on global gene expression in human adipocytes. SGBS adipocytes, differentiated in culture, were treated with macrophage-conditioned medium (U937 cells) for 4 or 24 h; control cells received unconditioned medium. Agilent arrays comprising 44,000 probes were used to analyse gene expression. Microarray analysis identified 1,088 genes differentially expressed in response to the conditioned medium at both 4 and 24 h (754 up-regulated, 334 down-regulated at 24 h); these included genes associated with inflammation and macrophage infiltration. A cluster of matrix metalloproteinase genes were highly up-regulated at both time-points, including MMP1, MMP3, MMP9, MMP10, MMP12 and MMP19. At 4 and 24 h, MMP1 was the most highly up-regulated gene (>2,400-fold increase in mRNA at 24 h). ELISA measurements indicated that substantial quantities of MMP1 and MMP3 were released from adipocytes incubated with conditioned medium, with little release by control adipocytes. Treatment with TNFalpha induced substantial increases in MMP1 (>100-fold) and MMP3 (27-fold) mRNA level and MMP1 and MMP3 release in adipocytes, suggesting that this cytokine could contribute to the stimulation of MMP expression by macrophages. In conclusion, macrophage-secreted factors induce a major inflammatory response in human adipocytes, with expression of MMP family members being strongly up-regulated. The induction of MMP1 and other MMPs suggests that macrophages stimulate tissue remodelling during adipose tissue expansion in obesity.