Systemic sclerosis-associated fibrosis

Luckhardt, Tracy; Thannickal, Victor J.

doi:10.1097/bor.0000000000000219

Cited by 35 publications

(18 citation statements)

References 55 publications

(40 reference statements)

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“…Autophagy and mitochondrial dysfunction, two other inter-related aging processes, have been implicated in SSc and other fibrotic diseases. Autophagy, a cellular proteostatic mechanism that targets damaged proteins and organelles for lysosomal degradation, and mitochondrial function both decline with aging, and impairments contribute to fibrosis in SSc and IPF as well as in animal models (see [17] for a detailed review).…”

Section: Molecular Mechanisms Of Agingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Premature and segmental activation of aging may contribute, among other pathologies, to autoimmunity [4], vascular abnormalities [5, 6], and fibrosis [7–17]. It is therefore not surprising that scleroderma, or systemic sclerosis (SSc), a disease characterized by the triad of autoimmune activation, vasculopathy, and fibrosis, has been described as a disease of accelerated aging [17]. The peak incidence of SSc occurs between ages 45 and 64 [18]; greater age at disease onset is a predictor of worse survival [19]; and systemic involvement such as cardiac, pulmonary, or renal disease is more common in elderly patients [20].…”

Section: Introductionmentioning

confidence: 99%

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Sirtuins and Accelerated Aging in Scleroderma

Wyman

Atamas

2018

Curr Rheumatol Rep

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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.

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Section: Molecular Mechanisms Of Agingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sirtuins and Accelerated Aging in Scleroderma

Wyman

Atamas

2018

Curr Rheumatol Rep

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“…For example, age-related biological changes have been observed in sclerosis-associated fibrosis (Luckhardt and Thannickal, 2015), anxiety disorders (Perna et al 2016), Down syndrome (Horvath et al 2015), and schizophrenia (Czepielewski et al 2016). In laboratory studies of HIV, accelerated aging has been observed through increased immune senescence associated with alterations in T-cell generation and gene expression (Boulias et al 2016; Chou et al 2013; Gianesin et al 2016; Pathai et al 2014) and resulting inflammation (for review, see Bhatia et al 2011).…”

mentioning

confidence: 99%

Accelerated and accentuated neurocognitive aging in HIV infection

et al. 2017

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There is debate as to whether the neurocognitive changes associated with HIV infection represent an acceleration of the typical aging process or more simply reflect a greater accentuated risk for age-related declines. We aimed to determine whether accelerated neurocognitive aging is observable in a sample of older HIV-infected individuals compared to age-matched seronegatives and older-old (i.e., aged ≥ 65) seronegative adults. Participants in a cross-sectional design included 48 HIV-seronegative (O−) and 40 HIV-positive (O+) participants between the ages of 50–65 (mean ages = 55 and 56, respectively) and 40 HIV-seronegative participants aged ≥ 65 (OO−; mean age = 74) who were comparable for other demographics. All participants were administered a brief neurocognitive battery of attention, episodic memory, speeded executive functions, and confrontation naming (i.e., Boston Naming Test). The O+ group performed more poorly than the O− group (i.e., accentuated aging), but not differently from the OO− on digit span and initial recall of a supraspan word list, consistent with an accelerating aging profile. However, the O+ group’s performance was comparable to the O− group on all other neurocognitive tests (ps > .05). These data partially support a model of accelerated neurocognitive aging in HIV-infection, which was observed in the domain of auditory verbal attention, but not in the areas of memory, language, or speeded executive functions. Future studies should examine whether HIV-infected adults over 65 evidence accelerated aging in downstream neurocognitive domains and subsequent everyday functioning outcomes.

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“…There is increasing evidence that SSc skin presents several hallmarks of cellular ageing, such as enhanced production of reactive oxygen species (ROS), methylation abnormalities and impaired autophagy . CCN1 has been associated with skin ageing in several studies .…”

Section: Ccn Proteins and Accelerated Ageingmentioning

confidence: 99%

CCN proteins as potential actionable targets in scleroderma

Henrot

Truchetet

Fisher

et al. 2018

Experimental Dermatology

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Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease combining inflammatory, vasculopathic and fibrotic manifestations. Skin features, which give their name to the disease and are considered as diagnostic as well as prognostic markers, have not been thoroughly investigated in terms of therapeutic targets. CCN proteins (CYR61/CCN1, CTGF/CCN2, NOV/CCN3 and WISP1‐2‐3 as CCN4‐5‐6) are a family of secreted matricellular proteins implicated in major cellular processes such as cell growth, migration, differentiation. They have already been implicated in key pathophysiological processes of SSc, namely fibrosis, vasculopathy and inflammation. In this review, we discuss the possible implication of CCN proteins in SSc pathogenesis, with a special focus on skin features, and identify the potential actionable CCN targets.

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Systemic sclerosis-associated fibrosis

Cited by 35 publications

References 55 publications

Sirtuins and Accelerated Aging in Scleroderma

Sirtuins and Accelerated Aging in Scleroderma

Accelerated and accentuated neurocognitive aging in HIV infection

CCN proteins as potential actionable targets in scleroderma

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