TLR2 and osteoarthritis: Extracellular HMGB1 triggers the secretion of inflammatory cytokines via the TLR2/4 and NF-κB signaling pathways, facilitating the production of secreted SASP.561,562 Blocking PRRs, such as TLR2 and TLR4, can alleviate cellular aging and age-related diseases,563 including osteoarthritis, vascular dysfunction in aged mice,564 and hair follicle cycle and regeneration565 (Fig. 14c).