Changes in expression and DNA methylation of SPARC in aging mice. SPARC mRNA expression (relative to gapdh) at different time points in life (b). Age-dependent changes in methylation of CG sites in the SPARC promoter (a) in IVDs as quantified by pyrosequencing (c). Treatment of 1-year old mice with the demethylating drug 5AC or vehicle (30 mg/kg, i.v. and 250 fmol i.t.) resulted in a 4-fold increase in SPARC mRNA expression and (d) decreased methylation of CG sites in the SPARC promoter as quantified by pyrosequencing in IVDs. Inset: Increased cold sensitivity following 5AC injection was significantly correlated with total SPARC methylation. * = p < 0.05, *** = p < 0.001. One-way ANOVA followed by Bonferroni's test (aging cohorts) and two-tailed student t-test (5AC vs. vehicle treated). Pearson's correlation (p = 0.03, r2 = 0.46). n = 3-15/group. Error bars = S.E.M.