Toward Elucidating Epigenetic and Metabolic Regulation of Stem Cell Lineage Plasticity in Skin Aging

The document investigated the epigenetic and metabolic regulation of stem cell lineage plasticity in skin aging, particularly focusing on hair follicle stem cells (HFSCs) and their role in hair follicle miniaturization. It found that aging leads to a decline in HFSCs, causing sparse hair and epidermal and sebaceous gland hyperplasia. Mechanisms such as epidermal transdifferentiation, apoptosis due to mechanical compression, and escape into the dermis were proposed for HFSC fate during aging. Genotoxic stress, including telomere attrition and DNA damage, accelerated aging, affecting HFSCs and leading to hair graying and alopecia. Nutritional and metabolic pathways like insulin/IGF, AMPK, mTOR, and sirtuins were implicated in skin aging. The study also highlighted the impact of calorie restriction and mitochondrial function on stem cell activity and aging, emphasizing the importance of transcriptional and epigenetic regulation, including heterochromatin silencing, in maintaining stem cell function. Understanding these mechanisms could inform therapeutic strategies for skin aging.