Hair regeneration by small molecules that activate autophagy

Hair plays important roles, ranging from the conservation of body heat to the preservation of psychological well-being. Hair loss or alopecia affects millions worldwide and can occur because of aging, hormonal dysfunction, autoimmunity, or as a side effect of cancer treatment (Gilhar et al., 2012; Petukhova et al., 2010). Methods that can be used to regrow hair are highly sought after, but lacking. Here we report that hair regeneration can be stimulated by small molecules that activate autophagy, including the longevity metabolites α-ketoglutarate and α-ketobutyrate, and the prescription drugs rapamycin and metformin which impinge on TOR and AMPK signaling.

[1]  R. Marotta,et al.  Autophagy is essential for maintaining the growth of a human (mini-)organ: Evidence from scalp hair follicle organ culture , 2018, PLoS biology.

[2]  N. Câmara,et al.  Caloric Restriction Promotes Structural and Metabolic Changes in the Skin. , 2017, Cell reports.

[3]  P. Sassone-Corsi,et al.  Aged Stem Cells Reprogram Their Daily Rhythmic Functions to Adapt to Stress , 2017, Cell.

[4]  Sheng-Cai Lin,et al.  Fructose-1,6-bisphosphate and aldolase mediate glucose sensing by AMPK , 2017, Nature.

[5]  T. Yoshimori,et al.  Faculty Opinions recommendation of Autophagy maintains the metabolism and function of young and old stem cells. , 2017 .

[6]  S. Kritchevsky,et al.  Metformin as a Tool to Target Aging. , 2016, Cell metabolism.

[7]  A. Christiano,et al.  Pharmacologic inhibition of JAK-STAT signaling promotes hair growth , 2015, Science Advances.

[8]  T. Graeber,et al.  2-Hydroxyglutarate Inhibits ATP Synthase and mTOR Signaling. , 2015, Cell metabolism.

[9]  D. Tobin,et al.  Mitochondrial function in murine skin epithelium is crucial for hair follicle morphogenesis and epithelial-mesenchymal interactions. , 2015, Journal of Investigative Dermatology.

[10]  K. Murao,et al.  Oxidative stress and substance P mediate psychological stress-induced autophagy and delay of hair growth in mice , 2015, Archives of Dermatological Research.

[11]  Keiji Tanaka,et al.  The significant role of autophagy in the granular layer in normal skin differentiation and hair growth , 2015, Archives of Dermatological Research.

[12]  Jiaxi Zhou,et al.  mTOR signaling promotes stem cell activation via counterbalancing BMP-mediated suppression during hair regeneration. , 2015, Journal of molecular cell biology.

[13]  Lorenzo Galluzzi,et al.  Metabolic Control of Autophagy , 2014, Cell.

[14]  T. Rando,et al.  Induction of autophagy supports the bioenergetic demands of quiescent muscle stem cell activation , 2014, The EMBO journal.

[15]  Yaning Sun,et al.  A mitochondrial ATP synthase subunit interacts with TOR signaling to modulate protein homeostasis and lifespan in Drosophila. , 2014, Cell reports.

[16]  William B. Mair,et al.  AMPK at the nexus of energetics and aging. , 2014, Cell metabolism.

[17]  Hilary A. Godwin,et al.  The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR , 2014, Nature.

[18]  Andrea Glasauer,et al.  Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis , 2014, eLife.

[19]  N. Mizushima,et al.  Expression of the autophagy substrate SQSTM1/p62 is restored during prolonged starvation depending on transcriptional upregulation and autophagy-derived amino acids , 2014, Autophagy.

[20]  D. Zheng,et al.  Nfatc1 orchestrates aging in hair follicle stem cells , 2013, Proceedings of the National Academy of Sciences.

[21]  G. Daley,et al.  Lin28 Enhances Tissue Repair by Reprogramming Cellular Metabolism , 2013, Cell.

[22]  Mingxing Lei,et al.  Therapeutic strategy for hair regeneration: hair cycle activation, niche environment modulation, wound-induced follicle neogenesis, and stem cell engineering , 2013, Expert opinion on biological therapy.

[23]  R. Deberardinis,et al.  Mitochondrial Reactive Oxygen Species Promote Epidermal Differentiation and Hair Follicle Development , 2013, Science Signaling.

[24]  M. Tauchi,et al.  Mammalian target of rapamycin complex 1 (mTORC1) may modulate the timing of anagen entry in mouse hair follicles , 2013, Experimental dermatology.

[25]  D. Hardie,et al.  AMPK: a nutrient and energy sensor that maintains energy homeostasis , 2012, Nature Reviews Molecular Cell Biology.

[26]  M. Fey,et al.  Autophagy is required for self-renewal and differentiation of adult human stem cells , 2011, Cell Research.

[27]  Jeffrey A Butler,et al.  Long‐lived mitochondrial (Mit) mutants of Caenorhabditis elegans utilize a novel metabolism , 2010, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[28]  Annette Lee,et al.  Genome-wide association study in alopecia areata implicates both innate and adaptive immunity , 2010, Nature.

[29]  L. Chodosh,et al.  mTOR mediates Wnt-induced epidermal stem cell exhaustion and aging. , 2009, Cell stem cell.

[30]  Ralf Paus,et al.  The Hair Follicle as a Dynamic Miniorgan , 2009, Current Biology.

[31]  Daniel J. Klionsky,et al.  Autophagy fights disease through cellular self-digestion , 2008, Nature.

[32]  Guido Kroemer,et al.  Autophagy in the Pathogenesis of Disease , 2008, Cell.

[33]  M. Driscoll,et al.  A Role for Autophagy in the Extension of Lifespan by Dietary Restriction in C. elegans , 2008, PLoS genetics.

[34]  Kailiang Jia,et al.  Autophagy is Required for Dietary Restriction-Mediated Life Span Extension in C. elegans , 2007, Autophagy.

[35]  Mayumi Ito,et al.  Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding , 2007, Nature.

[36]  S. Schreiber,et al.  Small molecules enhance autophagy and reduce toxicity in Huntington's disease models. , 2007, Nature chemical biology.

[37]  R Paus,et al.  A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages. , 2001, The Journal of investigative dermatology.

[38]  M. Owen,et al.  Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. , 2000, The Biochemical journal.

[39]  R. Paus,et al.  Melanogenesis is coupled to murine anagen: toward new concepts for the role of melanocytes and the regulation of melanogenesis in hair growth. , 1993, The Journal of investigative dermatology.

[40]  M. Hansen,et al.  A Role for Autophagy in the Extension of Lifespan by Dietary Restriction in -1 , 2011 .

[41]  J. M. Weitzner Alopecia areata. , 1990, American family physician.