Longevity associated mitochondrial metabolites in hair regeneration

Identification: Chai, Min


Description

Longevity associated mitochondrial metabolites in hair regeneration
 
Min Chai1, Meisheng Jiang2, Laurent Vergnes3, Karen Reue3,4 Jing Huang2, 4
1Molecular Biology Interdepartmental Doctoral Program, University of California Los Angeles, Los Angeles, California 90095, USA. 2Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA. 3Department of Human Genetics, University of California Los Angeles, Los Angeles, California 90095, USA. 4Molecular Biology Institute, University of California Los Angeles, Los Angeles, California 90095, USA
 
Hair loss and hair thinning can occur in numerous biological and pathological scenarios, among which deficient hair regeneration as a result of declined hair follicle stem cell (HFSC) function in aging is the least understood. HFSC activation and hair growth require appropriate mitochondrial function, homeostatic cellular redox, and signaling cues, all of which are impaired or dysregulated during aging and therefore cause dysfunction in aged HFSC. We hypothesized that hair loss and thinning resulting from reduced hair regeneration in aging can be alleviated by anti-aging remedies. In fact, various anti-aging approaches are shown to not only improve mitochondrial robustness but also restore stem cell function, suggesting that they may also stimulate hair regeneration. Remarkably, several mitochondrial metabolites have been shown to counteract aging and age-related degeneration and diseases. Metabolic programming also plays essential role in stem cell maintenance, activation and differentiation. These findings offer opportunities for transforming our understanding of anti-aging metabolites in promoting hair growth. Here we report on the induction of new hair follicle formation and hair regeneration by longevity-promoting mitochondrial metabolites in both young and aged mice. Another anti-aging remedy, calorie restriction, has also been shown to promotes hair follicle growth in mice, indicating a shared regulatory machinery of longevity and HFSC activation. Furthermore, using a combination of biochemical, genetic, and metabolomic approaches, we analyzed the molecular mechanisms underlying this new regulation. Taken together, our study identifies novel strategies and therapeutic opportunities for stimulating hair regeneration and may have implications for regenerative medicine involving other stem cells, tissues and organs.

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