Recent advances on skin-resident stem/progenitor cell functions in skin regeneration, aging and cancers and novel anti-aging and cancer therapies

Introduction Functions of skin-resident adult stem/progenitor cells in skin regeneration Altered functions of skin-resident adult stem/progenitor cells during chronological aging Potential implications of skin-resident stem/progenitor cells in skin aging-related disorders Animal models of skin-resident stem/progenitor cell aging and disorders Altered functions of skin-resident adult stem/progenitor cells in skin hyperproliferative disorders and cancers Potential implications of cancer stem/progenitor cells in basal cell and squamous cell cancers Potential implications of cancer stem/progenitor cells in melanoma Molecular events associated with melanoma progression Novel stem cell-based therapies Novel anti-aging therapies Modulation of aging process by calorie restriction and pharmacological agents Novel cell-replacement and gene therapies Novel cancer therapies targeting skin cancer stem/progenitor cells and their microenvironment Conclusions and future directions Recent advances in skin-resident adult stem/progenitor cell research have revealed that these immature and regenerative cells with a high longevity provide critical functions in maintaining skin homeostasis and repair after severe injuries along the lifespan of individuals. The establishment of the functional properties of distinct adult stem/progenitor cells found in skin epidermis and hair follicles and extrinsic signals from their niches, which are deregulated during their aging and malignant transformation, has significantly improved our understanding on the etiopathogenesis of diverse human skin disorders and cancers. Particularly, enhanced ultraviolet radiation exposure, inflammation and oxidative stress and telomere attrition during chronological aging may induce severe DNA damages and genomic instability in the skin-resident stem/progenitor cells and their progenies. These molecular events may result in the alterations in key signalling components controlling their self-renewal and/or regenerative capacities as well as the activation of tumour suppressor gene products that trigger their growth arrest and senescence or apoptotic death. The progressive decline in the regenerative functions and/or number of skin-resident adult stem/progenitor cells may cause diverse skin diseases with advancing age. Moreover, the photoaging, telomerase re-activation and occurrence of different oncogenic events in skin-resident adult stem/progenitor cells may also culminate in their malignant transformation into cancer stem/progenitor cells and skin cancer initiation and progression. Therefore, the anti-inflammatory and anti-oxidant treatments and stem cell-replacement and gene therapies as well as the molecular targeting of their malignant counterpart, skin cancer-initiating cells offer great promise to treat diverse skin disorders and cancers.