UVB increases oxidative stress and induces senescence in dermal papilla spheroids altering epithelial-mesenchymal interactions and hair follicle aging.

MARTINEZ, NAHUEL MATÍAS; HAGELIN, KARIN; BALAÑÁ, MARÍA EUGENIA; CERUTI, JULIETA MARÍA

MINNEAPOLIS

Congreso; 8th International Cell Senescence Association (ICSA) Conference; 2023

International Cell Senescence Association (ICSA)

The hair follicle is a compelling model in aging research, as its miniaturization and the hair lossare significant phenotypic traits of aging. Dermal papilla cells (DPC) regulate hair growth inducingdifferentiation of hair follicle stem cells (HFSC). DPC from bald patients have reducedproliferative capacity associated with premature cell senescence. This work aimed to generate amodel of UVB induced senescence in human DPC spheroids and to study its effect on HFSCdifferentiation. Repeated UVB exposure (4mJ/cm2, six times) upregulated expression ofsenescence associated secretory phenotype (SASP) factors (IL-1α, IL-1β, IL-6, MMP-1, PAI1),p16INK4a and p21Cip1 inhibitors and diminished laminB1 in DPC spheroids. UVB damaged DPCshowed cell cycle arrest, decreased metabolic activity and high SA-β- galactosidase activity (52%of cells). The percentage of UVB treated cells that suffered apoptosis or necrosis (9,34%) was notsignificant compared with untreated cells (13,84%). Catalase enzyme activity increased in a timedependent manner and percentage of ROS positive cells was significantly higher in UVBirradiated DPC, indicating elevated oxidative damage. Expression of Dkk-1, an inhibitor of HFSCdifferentiation was upregulated, whereas Wnt10b, known inducer of differentiation, wasdownregulated by UVB. Differentiation of keratinocytes derived from HFSC to hair lineage, wasimpaired when cultured in conditioned medium from UVB senescent DPC spheroids.Keratinocytes stopped proliferating and upregulated SASP expression. We conclude thatoxidative damage generated by UVB is a major factor that induces senescence, which in turn,diminishes inductivity in DPC spheroids. Moreover, keratinocytes evidence paracrine senescencefrom irradiated DPC, that would impair the differentiation to hair lineage. These findingsunderscore the influence of UVBinduced senescence on the crosstalk between epithelial (HFSCs)and mesenchymal (DPCs) compartments and shed light on potential targets for interventionsaimed at mitigating the deleterious effects of senescence in hair follicle aging.