Skin aging, the most visible and accessible manifestation of organismal aging, reflects systemic physiological decline, compromising barrier integrity, immune defense, and regenerative capacity-functions essential for overall tissue homeostasis and longevity. Understanding why and how the skin ages offers crucial insights into tissue homeostasis and systemic aging. Here, we dissect the multi-layered mechanisms of skin aging across the epidermis, dermis, and appendages, highlighting how intrinsic cellular senescence, disrupted inter-compartmental communication, and dysregulation of the skin microbiome and hormonal signaling collectively undermine epithelial structure and function. We also summarize advances in quantitative evaluation of skin aging, from molecular signatures to morphological, microbial, and phenotypic indices, enabling objective assessment of biological age and intervention efficacy. Finally, we highlight rejuvenation strategies, encompassing rewiring of gene expression programs, metabolic modulation, microenvironmental remodeling, microbiome modulation, and hormone regulation, offering a framework for precision interventions and next-generation regenerative therapies.
