Anne E Wyman1,2,3, Sergei P Atamas4,5. 1. Geriatric Research Education and Clinical Center (GRECC), VA Maryland Health Care Center, Baltimore VA Medical Center, Baltimore, MD, USA. 2. Research Service, Baltimore VA Medical Center, Baltimore, MD, 21201, USA. 3. Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Maryland School of Medicine, 10 S. Pine St., MSTF 834, Baltimore, MD, 21201, USA. 4. Research Service, Baltimore VA Medical Center, Baltimore, MD, 21201, USA. satamas@umaryland.edu. 5. Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Maryland School of Medicine, 10 S. Pine St., MSTF 834, Baltimore, MD, 21201, USA. satamas@umaryland.edu.
Abstract
PURPOSE OF REVIEW: Premature activation of aging-associated molecular mechanisms is emerging as an important contributor to many diseases, including scleroderma. Among central regulators of the aging process are a group of histone deacetylases called sirtuins (SIRTs). Recent findings implicate these molecules as pathophysiological players in scleroderma skin and lung fibrosis. The goal of this article is to review recent studies on the involvement of SIRTs in scleroderma from the perspective of aging-related molecular mechanisms. RECENT FINDINGS: Despite a degree of controversy in this rapidly developing field, the majority of data suggest that SIRT levels are decreased in tissues from patients with scleroderma compared to healthy controls as well as in animal models of scleroderma. Molecular studies reveal several mechanisms through which declining SIRT levels contribute to fibrosis, with the most attention given to modulation of the TGF-β signaling pathway. Activation of SIRTs in cell culture and in animal models elicits antifibrotic effects. Declining SIRT levels and activity are emerging as pathophysiological contributors to scleroderma. Restoration of SIRTs may be therapeutic in patients with scleroderma.
PURPOSE OF REVIEW: Premature activation of aging-associated molecular mechanisms is emerging as an important contributor to many diseases, including scleroderma. Among central regulators of the aging process are a group of histone deacetylases called sirtuins (SIRTs). Recent findings implicate these molecules as pathophysiological players in scleroderma skin and lung fibrosis. The goal of this article is to review recent studies on the involvement of SIRTs in scleroderma from the perspective of aging-related molecular mechanisms. RECENT FINDINGS: Despite a degree of controversy in this rapidly developing field, the majority of data suggest that SIRT levels are decreased in tissues from patients with scleroderma compared to healthy controls as well as in animal models of scleroderma. Molecular studies reveal several mechanisms through which declining SIRT levels contribute to fibrosis, with the most attention given to modulation of the TGF-β signaling pathway. Activation of SIRTs in cell culture and in animal models elicits antifibrotic effects. Declining SIRT levels and activity are emerging as pathophysiological contributors to scleroderma. Restoration of SIRTs may be therapeutic in patients with scleroderma.
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