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. 2020 May 12;32(1):44–55.e6. doi: 10.1016/j.cmet.2020.04.015

Figure 6.

Figure 6

Aging Promotes STAT3 Activation, Mitochondrial Localization, and IL17A/F Promoter Binding

(A and B) Quantification of STAT3 ser727 and the mitochondrial complex 1 subunit NDUFA13 localization in CD4+ T cells stimulated for 40 h with αCD3/αCD28 ± metformin as indicated. n = 4 with multiple field readings shown per N.

(C) Phospho (p)-STAT3 T705 expression assayed on western blots as indicated on x axis. n = 6–8.

(D) p-STAT3 T705 expression relative to total STAT3 in O cells in the presence of TEMP or MET. n = 4–5. ∗p < 0.05 versus Y or control siRNA or #p < 0.05 versus O. Fold change is compared with Y or O.

(A and D) 3 cells/field and 3–5 fields/slide were imaged using 63× oil immersion in Zeiss microscope. Average fluorescence/field is reported.

(E) Chromatin immunoprecipitation assay showing fold-enrichment of p-STAT3 705 on (left) IL-17A or (right) IL-17F promoters. n = 4. All bar graphs show mean ± SEM.

(F) Model for parallel metformin-sensitive pathways that drive T cell inflammaging. Activated T cells from O subjects displayed blunted autophagy, which was largely independent of changes in mitochondrial bioenergetics/excess ROS that promote STAT3-mediated activation of a CD4+ T cell inflammaging profile.