AD-GPT: large language models in Alzheimer's disease.

Androgenetic alopecia (AGA) is the most common form of hair loss in clinical practice [], characterized by progressive miniaturization of hair follicles [–] and clinical manifestations such as progressively reduced hair shaft diameter, decreased hair density, and varying degrees of baldness [, , ]. In China, the prevalence of AGA is approximately 21.3% in men and 6.0% in women []. This translates to an estimated 170 million patients in China alone, with hundreds of millions more affected worldwide. Its incidence increases with age [, –], and by age 70, at least 80% of men and 50% of women are affected []. AGA is not merely a cosmetic concern but also a condition that significantly impacts patients’ mental health, social confidence, and quality of life, thereby imposing a significant disease burden [, ]. It is now generally accepted that AGA development is driven by androgens in the context of genetic susceptibility [], although the specific mechanisms are complex and incompletely elucidated [, ]. While adjunctive approaches such as low-level laser therapy and platelet-rich plasma are increasingly available, the cornerstone of pharmacological treatment remains topical minoxidil and oral finasteride [, ]. Long-term management of AGA may be challenging due to its chronic progression and the interplay of genetic and environmental factors [, ]. Therefore, further research into the pathogenesis of AGA is necessary to develop more effective and targeted therapies. As the “command center” of hair follicles, dermal papilla cells (DPCs) play an irreplaceable role in hair follicle cycle regulation, morphology maintenance, and hair induction through the precise regulation of epithelial-mesenchymal interactions and key signaling pathways such as Wnt/β-catenin and BMP/TGF-β []. Hair follicle miniaturization is therefore thought to be due to abnormal dermal papilla (DP) function [, ], given that DP volume directly determines the size of the hair bulb and the diameter of the hair shaft, and influences the duration of the anagen phase. Single-cell analysis implicates DPCs as key drivers of AGA []. The current consensus is that AGA is androgen-driven in the context of genetic susceptibility, specifically dihydrotestosterone (DHT) acting on androgen receptors (AR) in DPCs at androgen-sensitive sites [], triggering downstream signaling cascades that lead to shortened anagen and prolonged telogen, culminating in progressive hair follicle miniaturization [, ]. However, the mechanism by which DHT causes the progressive functional decline of DPCs remains a key unresolved issue in the field. Cellular senescence is characterized by the loss of cellular function, cell cycle arrest, alterations in intercellular communication, disruption of protein homeostasis, and massive secretion of pro-inflammatory factors in response to injury and stress [, ]. In recent years, cellular senescence—a state of stable cell cycle arrest—has been shown to be closely associated with various age-related diseases [, ]. The incidence of AGA also increases with age [, , ], and consequently, its relationship with DPC senescence has garnered increasing attention. DPCs derived from the balding scalp of AGA patients rapidly exhibit a senescent phenotype in vitro [], whereas those from the non-balding scalp gradually become senescent after several passages and subsequently lose their ability to induce hair follicle formation [, ]. Senescent DPCs secrete elevated levels of IL-6, which inhibits the proliferation of hair follicle keratinocytes and the colony-forming capacity of hair follicle stem cells, and prevents the transition of hair follicles from the telogen to the anagen phase []. This effect is consistent with the pathological process of AGA. DHT-induced DPC senescence has been shown to some extent [–]. Therefore, DPC senescence is likely a key link between DHT stimulation and hair follicle dysfunction and may directly contribute to the pathological progression of AGA.