Stimulation of Hair Growth by Small Molecules that Activate Autophagy

Chai, Min; Jiang, Meisheng; Vergnes, Laurent; Fu, Xudong; Barros, Stéphanie C. de; Doan, Ngan; Huang, Wilson; Chu, Jessie; Jiao, Jing; Herschman, Harvey R.; Reue, Karen; Huang, Jing

doi:10.1016/j.celrep.2019.05.070

Cited by 99 publications

(102 citation statements)

References 63 publications

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“…Recently, small molecule activators of autophagy, such as alpha-ketoglutarate and alpha-ketobutyrate, were reported to induce a switch from telogen (the quiescent phase of the hair cycle) to anagen (the phase of active hair growth) in mice (Chai et al, 2019). Similarly, rapamycin and metformin stimulated growth of hair and their effects could be blocked by autophinib, an inhibitor of autophagosome formation (Chai et al, 2019). Studies in mouse models of alopecia and in humans are needed to determine whether the pharmacological activation of autophagy is able to counteract hair loss.…”

Section: Autophagy In Epithelial Cells Of the Skinmentioning

confidence: 99%

Autophagic Control of Skin Aging

Eckhart

Tschachler

Грубер

2019

Front. Cell Dev. Biol.

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The skin forms the barrier to the environment. Maintenance of this barrier during aging requires orchestrated responses to variable types of stress, the continuous renewal of the epithelial compartment, and the homeostasis of long-lived cell types. Recent experimental evidence suggests that autophagy is critically involved in skin homeostasis and skin aging is associated with and partially caused by defects of autophagy. In the outer skin epithelium, autophagy is constitutively active during cornification of keratinocytes and increases the resistance to environmental stress. Experimental suppression of autophagy in the absence of stress is tolerated by the rapidly renewing epidermal epithelium, whereas long-lived skin cells such as melanocytes, Merkel cells and secretory cells of sweat glands depend on autophagy for cellular homeostasis and normal execution of their functions during aging. Yet other important roles of autophagy have been identified in the dermis where senescence of mesenchymal cells and alterations of the extracellular matrix (ECM) are hallmarks of aging. Here, we review the evidence for cell type-specific roles of autophagy in the skin and their differential contributions to aging.

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Section: Autophagy In Epithelial Cells Of the Skinmentioning

confidence: 99%

Autophagic Control of Skin Aging

Eckhart

Tschachler

Грубер

2019

Front. Cell Dev. Biol.

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“…To assess whether Sirt7 regulates adult hair growth, we shaved the hair coat of female Sirt7 +/+ and Sirt7 À/À mice on postnatal day (P) 60, when the HFs of both genotypes were in the second telogen phase ( Fig 1A). We evaluated hair coat recovery based on skin pigmentation and hair shaft growth as described Chai et al, 2019). By P120, Sirt7 +/+ mice recovered an almost full hair coat, while the Sirt7 À/À mice showed only~25% recovery (Fig 1A and B).…”

Section: Resultsmentioning

confidence: 99%

“…Hair cycle analyses were based on skin pigmentation, as previously described . In brief, shaved hair coat recovery values from 0 to 100% were calculated based on skin pigmentation levels and hair shaft density (Chai et al, 2019). For example, 0% indicated no hair growth (and no pigmentation); 50% indicated fulllength hair growth on 50% of the dorsal skin area or pigmentation on 100% of the dorsal skin area without hair shafts; 70% indicated full-length hair growth on 70% of the dorsal skin or pigmentation on 100% of dorsal skin with 30-40% hair shafts; 100% indicated full-length hair growth on 100% of the dorsal skin.…”

Section: Hair Cycle Analysismentioning

confidence: 99%

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SIRT 7 activates quiescent hair follicle stem cells to ensure hair growth in mice

Tang

Zhang

et al. 2020

The EMBO Journal

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Hair follicle stem cells (HFSCs) are maintained in a quiescent state until activated to grow, but the mechanisms that reactivate the quiescent HFSC reservoir are unclear. Here, we find that loss of Sirt7 in mice impedes hair follicle life‐cycle transition from telogen to anagen phase, resulting in delay of hair growth. Conversely, Sirt7 overexpression during telogen phase facilitated HSFC anagen entry and accelerated hair growth. Mechanistically, Sirt7 is upregulated in HFSCs during the telogen‐to‐anagen transition, and HFSC‐specific Sirt7 knockout mice (Sirt7f/f;K15‐Cre) exhibit a similar hair growth delay. At the molecular level, Sirt7 interacts with and deacetylates the transcriptional regulator Nfatc1 at K612, causing PA28γ‐dependent proteasomal degradation to terminate Nfatc1‐mediated telogen quiescence and boost anagen entry. Cyclosporin A, a potent calcineurin inhibitor, suppresses nuclear retention of Nfatc1, abrogates hair follicle cycle delay, and promotes hair growth in Sirt7−/− mice. Furthermore, Sirt7 is downregulated in aged HFSCs, and exogenous Sirt7 overexpression promotes hair growth in aged animals. These data reveal that Sirt7 activates HFSCs by destabilizing Nfatc1 to ensure hair follicle cycle initiation.

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“…A second, more recent article, provides additional support to the importance of autophagy. [ 73 ] This time utilizing a murine model (C57BL/6J mouse), the authors demonstrate that autophagy increases during anagen phase of the normal hair cycle, is reduced during catagen and remains low during telogen. Furthermore, using several compounds that induce autophagy, including the metabolite α‐ketoglutarate and the mTOR inhibitor rapamycin, it was demonstrated that treatment of HFs in telogen phase resulted in accelerated HF regeneration.…”

Section: Autophagy As An Element Of Hair Growth Controlmentioning

confidence: 99%

The Hair Follicle as an Interdisciplinary Model for Biomedical Research: An Eclectic Literature Synthesis

Haslam

Paus

2020

BioEssays

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Skin is a comparatively accessible organ possessing many conserved regulatory and signaling pathways, drawing researchers from varied fields toward its study. Hair follicle (HF) biology in particular has expanded rapidly over the preceding decade, helping to shape and develop scientific knowledge across diverse areas of biomedical research, beyond the skin. The hope in compiling this review is to inspire more researchers to utilize the HF as an instructive biological model, bringing with them fresh perspectives and experience from differing fields of study. The authors also wish to further motivate seasoned hair researchers to explore the further reaches of their understanding and the discoveries yet to be made. For this reason, the authors have endeavored to collate an eclectic mix of some of the most thought-provoking and scientifically intriguing articles associated with the field of HF research, published in the preceding two years.

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Stimulation of Hair Growth by Small Molecules that Activate Autophagy

Cited by 99 publications

References 63 publications

Autophagic Control of Skin Aging

Autophagic Control of Skin Aging

SIRT 7 activates quiescent hair follicle stem cells to ensure hair growth in mice

The Hair Follicle as an Interdisciplinary Model for Biomedical Research: An Eclectic Literature Synthesis

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