Title:
Hair follicle aging and stem cell regulation
Emi K. Nishimura (Dept. of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University )
Abstract:
Multicellular organisms senesce with the expression of various aging phenotypes characterized by functional tissue decline and organismal changes with decreased regenerating capabilities. Hair loss and hair graying are typical aging phenotypes in mammals, but the underlying mechanisms of aging are still largely elusive in most tissues. In recent decades, some signaling pathways which determine organismal lif espan and molecules responsible for progeroid syndromes have been identified in some organisms, but the underlying cellular mechanisms of aging-associated tissue decline and diseases are still largely unknown. We have studied the mechanisms of aging-associated hair graying and hair loss by focusing on adult stem cells. We previously identified melanocyte stem cells (McSC) within the bulge-subbulge area of mouse hair follicles. The population is cyclically activated to self-renew and to provide mature melanocytes for hair pigmentation (Nishimura EK et al. 2002). Our chronological analysis of McSCs and hair follicle stem cells (HFSCs), the niche for McSCs, demonstrated that mouse hair follicles age through defective renewal of McSCs and HFSCs. McSCs differentiate into pigment-producing melanocytes in the niche without renewing themselves under excessive genomic stress or with aging (Inomata K et al. 2009). Strikingly, HFSCs with a sustained DNA damage response also showed characteristic fate changes which are clearly distinguished from cellular senescence. The stem cell fate changes with aging and the underlying mechanisms of tissue aging will be illustrated and discussed.
References:
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5. Nishimura, E.K, Granter, S.R., Fisher, D.E. Mechanisms of hair graying: incomplete melanocyte stem cell maintenance in the niche Science. 307(5710):720-724. 2005
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