Sirtuins and Accelerated Aging in Scleroderma

Scleroderma (J Varga, Section Editor)
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Part of the following topical collections:
  1. Topical Collection on Scleroderma

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.

Summary

Declining SIRT levels and activity are emerging as pathophysiological contributors to scleroderma. Restoration of SIRTs may be therapeutic in patients with scleroderma.

Keywords

Scleroderma Systemic sclerosis SSc Fibrosis Sirtuin SIRT Aging Skin Lung Fibroblast 

Notes

Acknowledgements

The authors’ studies are supported by a Scleroderma Foundation award, National Institutes of Health Grant R01HL126897 from NHLBI, and by Veterans Affairs Merit Award I01BX002499 (all to S. P. A.)

Compliance with Ethical Standards

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Copyright information

© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2018

Authors and Affiliations

  1. 1.Geriatric Research Education and Clinical Center (GRECC), VA Maryland Health Care CenterBaltimore VA Medical CenterBaltimoreUSA
  2. 2.Research ServiceBaltimore VA Medical CenterBaltimoreUSA
  3. 3.Division of Rheumatology and Clinical Immunology, Department of MedicineUniversity of Maryland School of MedicineBaltimoreUSA

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