Genotoxic stress abrogates renewal of melanocyte stem cells by triggering their differentiation.

Somatic stem cell depletion due to the accumulation of DNA damage has been implicated in the appearance of aging-related phenotypes. Hair graying, a typical sign of aging in mammals, is caused by the incomplete maintenance of melanocyte stem cells (MSCs) with age. Here, we report that irreparable DNA damage, as caused by ionizing radiation, abrogates renewal of MSCs in mice. Surprisingly, the DNA-damage response triggers MSC differentiation into mature melanocytes in the niche, rather than inducing their apoptosis or senescence. The resulting MSC depletion leads to irreversible hair graying. Furthermore, deficiency of Ataxia-telangiectasia mutated (ATM), a central transducer kinase of the DNA-damage response, sensitizes MSCs to ectopic differentiation, demonstrating that the kinase protects MSCs from their premature differentiation by functioning as a "stemness checkpoint" to maintain the stem cell quality and quantity.

Single-cell analysis of human dermal fibroblasts isolated from a single male donor over 35 years.

The aim of this study is to examine the effects of ageing on dermal fibroblast heterogeneity based on samples obtained from the same donor. We used a dermal fibroblast lineage (named ASF-4 cell lines) isolated from the inner side of the upper arm of a healthy male donor over a 35-year period, beginning at 36 years of age. Because clonal analysis of ASF-4 cell lines demonstrated a donor age-dependent loss of proliferative capacity and acquisition of senescent traits at the single-cell level, cultured cells frozen at passage 10 at ages 36 and 72 years were subjected to single-cell RNA sequencing. Transcriptome analysis revealed an increase in senescent fibroblasts and downregulation of genes associated with extracellular matrix remodelling with ageing. In addition, two putative differentiation pathways, with one endpoint consisting of senescent fibroblasts and the other without, were speculated using a pseudo-time analysis. Knockdown of the characteristic gene of the non-senescent fibroblast cluster endpoint, EFEMP2, accelerated cellular senescence. This was also confirmed in two other normal human dermal fibroblast cell lines. The detection of a common cellular senescence-related gene from single-donor analysis is notable. This study provides new insights into the behaviour of dermal fibroblasts during skin ageing.

Objective analysis of the effectiveness of facial massage using breakthrough computed tomographic technology: A preliminary pilot study.

BACKGROUND: Facial massage is empirically known to be associated with morphological changes, such as improvements in facial sagging. However, quantified objective evaluations of massage-induced changes have not been performed to date. This preliminary pilot study aimed to verify the effectiveness of facial massages by using breakthrough computed tomographic technology. MATERIALS AND METHODS: Five healthy adult volunteers (three women and two men; age, 29-37 years) were enrolled, and computed tomography (CT) examinations using a 320 detectors-spiral CT system known as 320-multidetector-row CT (MDCT) were performed before and after facial massages. Each participant performed a self-massage twice daily for 2 weeks. Massage-induced changes in the cheeks and the superficial musculoaponeurotic system (SMAS) were analyzed by two radiologists on a workstation with a high-accuracy imaging analysis system. RESULTS: After facial massage, the malar top became thinner by -0.8% ± 0.45% and shifted cranially and horizontally over a distance of 3.9 ± 1.94 mm. The SMAS-height, defined as the highest vertical distance of the SMAS, increased by 2.6% ± 2.6%. The change rate in cheek thickness and SMAS-height showed a significant correlation (r = -0.63; P < 0.05). These changes were attributed to the lifting and tightening effects of facial massage. CONCLUSION: We conducted a detailed analysis of the effects of facial massages by using the breakthrough CT technology. Our results provide useful information for beauty treatments and could contribute to the collection of objective scientific evidence for facial massages.

Hair follicle stem cells provide a functional niche for melanocyte stem cells.

In most stem cell systems, the organization of the stem cell niche and the anchoring matrix required for stem cell maintenance are largely unknown. We report here that collagen XVII (COL17A1/BP180/BPAG2), a hemidesmosomal transmembrane collagen, is highly expressed in hair follicle stem cells (HFSCs) and is required for the maintenance not only of HFSCs but also of melanocyte stem cells (MSCs), which do not express Col17a1 but directly adhere to HFSCs. Mice lacking Col17a1 show premature hair graying and hair loss. Analysis of Col17a1-null mice revealed that COL17A1 is critical for the self-renewal of HFSCs through maintaining their quiescence and immaturity, potentially explaining the mechanism underlying hair loss in human COL17A1 deficiency. Moreover, forced expression of COL17A1 in basal keratinocytes, including HFSCs, in Col17a1-null mice rescues MSCs from premature differentiation and restores TGF-ß signaling, demonstrating that HFSCs function as a critical regulatory component of the MSC niche.

Donor age-dependent acceleration of cellular aging by repeated ultraviolet A irradiation of human dermal fibroblasts derived from a single donor.

The relationship between cellular aging and aging of entire organisms has been studied extensively.The findings are confusing, however, and no clear relationships have been demonstrated.The conflicting data may be due to individual differences among the donors of the studied cells.It is crucial to identify the changes in cellular properties that are the result of the aging process.Here, we used human dermal fibroblast cell lines established from a single donor at different ages to assess the influence of ultraviolet A (UVA) on cellular aging. These cell lines have the same genetic background and were obtained from a restricted body region. The results indicated that cellular aging was accelerated by UVA irradiation in a donor age-dependent manner. The ratio of lifespan shortening increased with donor age. Increased donor age not only decreased cell division, but also increased the growth arrest response to UVA irradiation. The characteristics of the cultured cells reflected the age-related changes in dermal fibroblasts.