SIRT1 and rheumatoid arthritis: Nuclear-localized Sirt1 is involved in anti-apoptosis, whereas cytoplasmically localized Sirt1 promote apoptosis that is independent of de-acetylation but dependent on Caspase signaling.32, 33 Moreover, overexpression and nuclear-localization of Sirt1 significantly promotes apoptotic resistance in RA-FLSs.25 Thus, the subcellular localization of Sirt1 in FLSs may be pivotal to RA progression.