Figure 5. TB induced cellular senescence and premature cellular aging. (A) Humans and guinea pigs with TB demonstrated DNA hypermethylation gene changes that enriched for the SASP and OSIS pathways (Reactome overrepresentation p-values). (B) Hypermethylated genes in CD8+ T cells from patients with TB statistically overlapped with old age-associated closed chromatin conformation changes. (C) Multiplex ELISA of senescence associated proteins in patients with TB compared to healthy controls. (D) Epigenetic age (using the Horvath DNA methylation clock) is increased as compared to chronological age in TB patients at baseline and 6 months after the completion of successful anti-TB therapy. (E) Difference between chronological age and biological age using the RNA age calculator demonstrates an increase in TB patients compared to healthy controls (one-way ANOVA with Tukey’s multiple comparison).