UVB INCREASES OXIDATIVE STRESS AND INDUCES SENESCENCE IN DERMAL PAPILLA SPHEROIDS ALTERING EPITHELIAL-MESENCHYMAL INTERACTIONS THAT AFFECT HAIR FOLLICLE AGING

MARTINEZ , NAHUEL; HAGELIN KARIN; BALAÑA MARÍA EUGENIA; CERUTI, JULIETA MARÍA

Mar del Plata

Congreso; Reunión de Sociedades de Biociencias:; 2023

SAIC

The hair follicle is a compelling model in aging research, as its miniaturization and thehair loss are significant phenotypic traits of aging. Dermal papilla cells (DPC) regulatecyclic hair growth by inducing differentiation of hair follicle stem cells (HFSC). DPC frombald patients have reduced proliferative capacity associated with premature cellsenescence. We previously established a 3D model of UVB-induced senescence inhuman DPC spheroids and observed that senescent DPC lose their inductivity on HFSCdifferentiation. We further characterized this model and explored the impact of senescentDPC on paracrine senescence in keratinocytes. Repeated UVB exposure (4mJ/cm2, sixtimes) upregulated expression of senescence associated secretory phenotype (SASP)factors (IL-1α, IL-1β, IL-6, MMP-1 and PAI) accentuating the pro-inflammatory milieu anddiminished laminB1 marker in DPC spheroids. Moreover, catalase enzyme activityincreased in a time dependent manner (UVB 2.11-fold vs Control at 24h) and percentageof ROS positive cells was significantly higher in UVB irradiated DPC, indicating elevatedoxidative damage. Also, Dkk-1, an inhibitor of HFSC differentiation was upregulated,whereas Wnt10b, known inducer of differentiation, was downregulated by UVB.Keratinocytes derived from HFSC stop proliferating and upregulate SASP expressionwhen cultured with conditioned medium from irradiated DPC spheroids. We concludethat oxidative damage generated by UVB is a major factor that induces senescence,which in turn, diminishes inductivity in DPC spheroids. Moreover, keratinocytes showedparacrine senescence from irradiated DPC, that would impair their differentiation to hairlineage. These findings underscore the disruptive influence of UVB-induced senescenceon the crosstalk between epithelial (HFSCs) and mesenchymal (DPCs) compartmentsand shed light on potential targets for interventions aimed at mitigating the deleteriouseffects of senescence in hair follicle aging.