Taken together, these findings suggest that SIRT3 might have an important negative regulatory function to check TGF-β-dependent fibrotic responses in fibroblasts, and its deficiency in SSc, possibly reflecting its down-regulation by TGF-β within the fibrotic milieu, might play a causal role in the persistence of fibrosis in these tissues. The gene discussed is SIRT3; the disease is systemic sclerosis.