Telomere dysfunction impairs epidermal stem cell specification and differentiation by disrupting BMP/pSmad/P63 signaling

by Na Liu, Yu Yin, Haiying Wang, Zhongcheng Zhou, Xiaoyan Sheng, Haifeng Fu, Renpeng Guo, Hua Wang, Jiao Yang, Peng Gong, Wen Ning, Zhenyu Ju, Yifei Liu, Lin Liu Telomere shortening is associated with aging and age-associated diseases. Additionally, telomere dysfunction resulting from telomerase gene mutation can lead to premature aging, such as apparent skin atrophy and hair loss. However, the molecular signaling linking telomere dysfunction to skin atrop hy remains elusive. Here we show that dysfunctional telomere disrupts BMP/pSmad/P63 signaling, impairing epidermal stem cell specification and differentiation of skin and hair follicles. We find that telomere shortening mediated byTerc loss up-regulatesFollistatin (Fst), inhibiting pSmad signaling and down-regulatingP63 and epidermal keratins in an ESC differentiation model as well as in adult development of telomere-shortened mice. Mechanistically, short telomeres disrupt PRC2/H3K27me3-mediated repression ofFst. Our findings reveal that skin atrophy due to telomere dysfunction is caused by a previously unappreciated link with Fst and BMP signaling that could be explored in the development of therapies.
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research

Related Links:

In this study, we hypothesized that moderately and chronically reducing ACh could attenuate the deleterious effects of aging on NMJs and skeletal muscles. To test this hypothesis, we analyzed NMJs and muscle fibers from heterozygous transgenic mice with reduced expression of the vesicular ACh transporter (VAChT), VKDHet mice, which present with approximately 30% less synaptic ACh compared to control mice. Because ACh is constitutively decreased in VKDHet, we first analyzed developing NMJs and muscle fibers. We found no obvious morphological or molecular differences between NMJs and muscle fibers of VKDHet and contro...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Quercetin is used in combination with dasatinib as a senolytic treatment capable of selectively destroying senescent cells, but quercetin used by itself is not meaningfully senolytic. Researchers here show that long term low dosage with quercetin modestly slows aspects of aging in mice, however, without extending life span. They evaluate a number of potential mechanisms, including possible reductions of the inflammatory signaling secreted by senescent cells. All in all an interesting paper, particularly for the investigation of effects on retrotransposons. I expect that most interventions shown to slow aging will turn out ...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
Conclusion: After exposure to primary physical or mental stressor, hair follicles are stimulated to enter prematurely into telogen and shed out. In individuals with Taq1 and Cdx1 polymorphisms, the disease persists as a result of prevention of new anagen growth and inhibition of hair follicle stem cell proliferation. PMID: 31632122 [PubMed]
Source: Clinical, Cosmetic and Investigational Dermatology - Category: Dermatology Tags: Clin Cosmet Investig Dermatol Source Type: research
In conclusion, a polypharmacology approach of combining established, prolongevity drug inhibitors of specific nodes may be the most effective way to target the nutrient-sensing network to improve late-life health. Deletion of p38α in Neurons Slows Neural Stem Cell Decline and Loss of Cognitive Function in Mice Researchers here provide evidence for p38α to be involved in the regulation of diminished neural stem cell activity with age. It is thought...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
The SENS Research Foundation should need no introduction to this audience, but, just in case, this is one of the few non-profit organizations dedicated to advancing the state of the art in rejuvenation research and development. The focus of the SENS Research Foundation staff is on unblocking lines of research that are presently moving too slowly, rather than on reinforcing success. The co-founder, Aubrey de Grey, assembled the Strategies for Engineered Negligible Senescence (SENS) going on twenty years ago. It was, and is, a synthesis of what is known in the research community regarding the root causes of aging. In the SEN...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
Authors: Xia J, Minamino S, Kuwabara K, Arai S Abstract Stem cells are an undifferentiated cell population that has the ability to develop into many different cell types and also has the ability to repair damaged tissues in some cases. For a long time, the stem cell regenerative paradigm has been based on the assumption that progenitor cells play a critical role in tissue repair by means of their plasticity and differentiation potential. However, recent works suggest that the mechanism underlying the benefits of stem cell transplantation might relate to a paracrine modulatory effect rather than the replacement of a...
Source: BioScience Trends - Category: Biomedical Science Tags: Biosci Trends Source Type: research
The regenerative nature of hair follicle (HF) stem cells (SCs) facilitates HF cycling and support skin regeneration. A reduction in HF SC number is a key factor in skin and HF aging and in the development of hair disorders, i.e. androgenetic alopecia and lichen planopilaris. Fruit SC-derived extracts reportedly have positive effects on the regenerative capacity of primary human epidermal SCs. Treatment with apple or grape SC extract increased the colony forming efficacy of primary human epidermal SCs, even under UV stimulation, and restored the organogenic potential of late passage primary human epidermal SCs to generate 3...
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Stem Cells, Skin Appendages and Tissue Regeneration Source Type: research
Hair transplantation is used routinely for the management of androgenetic alopecia, the most common cause of hair loss. However, patients must have enough donor hair follicles (HFs) for transplant surgery. Alternative technologies that could potentially generate HFs in vitro would be beneficial. Efforts to recapitulate HF morphogenesis, using mouse embryonic cells or primary human adult epidermal or outer root sheath (ORS) keratinocytes, in combination with human primary dermal papilla fibroblasts (DPs), have been largely unsuccessful.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Stem Cells, Skin Appendages and Tissue Regeneration Source Type: research
Androgenic alopecia affects hair follicles (HFs) from frontal and vertex area. Hair inductive properties of DPCs are lost in bi-dimentional (2D) culture. In a recent study three dimentional (3D) structure of cultured DPCs was able to recapitulate 22% of molecular signature of the intact dermal papilla. The aim of this study is to compare gene expression differences between DPCs from balding scalp and non balding scalp (occipital area) and their changes in 2D and 3D cultures. We investigated whether 3D structure of these immortalized cells and their co-culture with ASCs could increase the expression of hair inductivity markers.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Stem Cells, Skin Appendages and Tissue Regeneration Source Type: research
In oncology, permanent chemotherapy-induced alopecia (pCIA) remains an unfulfilled clinical need. Irreversible hair loss may result from permanent damage of hair follicle bulge epithelial stem cells (HFeSCs), some of which may undergo epithelial-mesenchymal transition (EMT). To prove our hypothesis, we treated ex vivo full-length HFs with 4HC, a cyclophosphamide metabolite 4HC, which routinely induces reversible CIA and sometimes pCIA. PPAR γ signaling is known to have a protective role in eSCs biology.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Stem Cells, Skin Appendages and Tissue Regeneration Source Type: research
More News: Alopecia | Genetics | Skin | Stem Cell Therapy | Stem Cells