Pgc-1α controls epidermal stem cell fate and skin repair by sustaining NAD+ homeostasis during aging

Wong, Wesley; Crane, Elizabeth D.; Zhang, Hui; Li, Jiahe; Day, Tovah; Green, Alex E.; Menzies, Keir J.; Crane, Justin D.

doi:10.1016/j.molmet.2022.101575

Cited by 11 publications

(9 citation statements)

References 60 publications

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“…For example, a recent study investigated the effect of aging on the expression of peroxisome proliferator activator-γ coactivator-1 (PGC1α) in mouse skin. This study showed reduced epidermal PGC1α levels with aging; in addition, this decrease was associated with delayed wound healing in aged mice [77], suggesting a possible role for this co-activator in aging-related skin changes. Indeed, a conditional knockout mouse model with an epidermal-specific ablation of the gene encoding PGC1α exhibited decreased keratinocyte proliferation and delayed wound healing, demonstrating the importance of this protein to skin function [77].…”

Section: Possible Mechanisms Of Skin Dysfunction With Agementioning

confidence: 52%

“…This study showed reduced epidermal PGC1α levels with aging; in addition, this decrease was associated with delayed wound healing in aged mice [77], suggesting a possible role for this co-activator in aging-related skin changes. Indeed, a conditional knockout mouse model with an epidermal-specific ablation of the gene encoding PGC1α exhibited decreased keratinocyte proliferation and delayed wound healing, demonstrating the importance of this protein to skin function [77]. These results support the potential involvement of PGC1α in some (or perhaps all) of the deficiencies associated with age.…”

Section: Possible Mechanisms Of Skin Dysfunction With Agementioning

confidence: 52%

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The Skin and Inflamm-Aging

Agrawal,

Hu,

Bollag

2023

Biology

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With its unique anatomical location facing both the external and internal environment, the skin has crucial functions, including shielding the body from damage caused by ultraviolet radiation and chemicals, preventing water loss, acting as a primary barrier against pathogens, participating in metabolic processes like vitamin D production and temperature control and relaying information to the body through sensory and proprioceptor nerves. Like all organ systems, skin is known to undergo multiple changes with aging. A better understanding of the mechanisms that mediate aging-related skin dysfunction may allow the creation of targeted therapeutics that have beneficial effects not only on aged skin but also on other organs and tissues that experience a loss of or decline in function with aging. The skin is the largest organ of the body and can contribute to serum inflammatory mediator levels. One alteration known to occur with age is an impairment of skin barrier function; since disruption of the barrier is known to induce inflammation, skin may be a major contributor to the sustained, sub-clinical systemic inflammation associated with aging. Such “inflamm-aging” may underlie many of the deleterious changes observed in aged individuals. This review explores the role of age-related skin changes, skin inflammation and inflamm-aging.

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Section: Possible Mechanisms Of Skin Dysfunction With Agementioning

confidence: 52%

Section: Possible Mechanisms Of Skin Dysfunction With Agementioning

confidence: 52%

The Skin and Inflamm-Aging

Agrawal,

Hu,

Bollag

2023

Biology

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“…PGC-1α is a transcriptional coactivator involved in the regulation of metabolism and mitochondrial function in several tissues and organs [ 88 , 89 ]. Wong et al [ 90 ] reported that PGC-1α plays an essential role in NAD homeostasis during skin aging. NAD is involved in the regulation of cell growth under physiological stress conditions in the skin interacting with the p53/p21 signaling pathway.…”

Section: Potential Interaction Of the Ppar Signaling Pathway And The ...mentioning

confidence: 99%

“…NAD is involved in the regulation of cell growth under physiological stress conditions in the skin interacting with the p53/p21 signaling pathway. Importantly, PGC-1α sustains the level of NAD, which is crucial for epidermal repair [ 90 ].…”

Section: Potential Interaction Of the Ppar Signaling Pathway And The ...mentioning

confidence: 99%

“…PGC-1α plays an important role in the regulation of physiological processes within the skin. A recent study indicated the crucial role of PGC-1α in epidermal repair [ 90 ]. Additionally, Shoag et al reported that this transcriptional coactivator regulated the production of melanin interacting with microphthalmia-associated transcription factor (MITF) [ 94 ].…”

Section: Potential Interaction Of the Ppar Signaling Pathway And The ...mentioning

confidence: 99%

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PPARs and the Kynurenine Pathway in Melanoma—Potential Biological Interactions

Walczak

Gerkowicz

Krasowska

2023

IJMS

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Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors involved in various physiological and pathological processes within the skin. PPARs regulate several processes in one of the most aggressive skin cancers, melanoma, including proliferation, cell cycle, metabolic homeostasis, cell death, and metastasis. In this review, we focused not only on the biological activity of PPAR isoforms in melanoma initiation, progression, and metastasis but also on potential biological interactions between the PPAR signaling and the kynurenine pathways. The kynurenine pathway is a major pathway of tryptophan metabolism leading to nicotinamide adenine dinucleotide (NAD+) production. Importantly, various tryptophan metabolites exert biological activity toward cancer cells, including melanoma. Previous studies confirmed the functional relationship between PPAR and the kynurenine pathway in skeletal muscles. Despite the fact this interaction has not been reported in melanoma to date, some bioinformatics data and biological activity of PPAR ligands and tryptophan metabolites may suggest a potential involvement of these metabolic and signaling pathways in melanoma initiation, progression, and metastasis. Importantly, the possible relationship between the PPAR signaling pathway and the kynurenine pathway may relate not only to the direct biological effect on melanoma cells but also to the tumor microenvironment and the immune system.

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PGC1α‐Inducing Senomorphic Nanotherapeutics Functionalized with NKG2D‐Overexpressing Cell Membranes for Intervertebral Disc Degeneration

Liu,

Li,

et al. 2024

Advanced Science

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Cellular senescence is a significant contributor to intervertebral disc aging and degeneration. However, the application of senotherapies, such as senomorphics targeting senescence markers and the senescence‐associated secretory phenotype (SASP), remains limited due to challenges in precise delivery. Given that the natural killer group 2D (NKG2D) ligands are increased on the surface of senescent nucleus pulposus (NP) cells, the NKG2D‐overexpressing NP cell membranes (NNPm) are constructed, which is expected to achieve a dual targeting effect toward senescent NP cells based on homologous membrane fusion and the NKG2D‐mediated immunosurveillance mechanism. Then, mesoporous silica nanoparticles carrying a peroxisome proliferator‐activated receptor‐ɣ coactivator 1α (PGC1α)inducer (SP) are coated with NNPm (SP@NNPm) and it is found that SP@NNPm selectively targets senescent NP cells, and the SP cores exhibit pH‐responsive drug release. Moreover, SP@NNPm effectively induces PGC1α‐mediated mitochondrial biogenesis and mitigates senescence‐associated markers induced by oxidative stress and the SASP, thereby alleviating puncture‐induced senescence and disc degeneration. This dual‐targeting nanotherapeutic system represents a novel approach to delivery senomorphics for disc degeneration treatment.

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Pgc-1α controls epidermal stem cell fate and skin repair by sustaining NAD+ homeostasis during aging

Cited by 11 publications

References 60 publications

The Skin and Inflamm-Aging

The Skin and Inflamm-Aging

PPARs and the Kynurenine Pathway in Melanoma—Potential Biological Interactions

PGC1α‐Inducing Senomorphic Nanotherapeutics Functionalized with NKG2D‐Overexpressing Cell Membranes for Intervertebral Disc Degeneration

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