Aging and homeostasis of the hypodermis in the age-related deterioration of skin function

Abstract Adipose tissues in the hypodermis, the crucial stem cell reservoir in the skin and the endocrine organ for the maintenance of skin homeostasis undergo significant changes during skin aging. Dermal white adipose tissue (dWAT) has recently been recognized as an important organ for both non-metabolic and metabolic health in skin regeneration and rejuvenation. Defective differentiation, adipogenesis, improper adipocytokine production, and immunological dissonance dysfunction in dWAT lead to age-associated clinical changes. Here, we review age-related alterations in dWAT across levels, emphasizing the mechanisms underlying the regulation of aging. We also discuss the pathogenic changes involved in age-related fat dysfunction and the unfavorable consequences of accelerated skin aging, such as chronic inflammaging, immunosenescence, delayed wound healing, and fibrosis. Research has shown that adipose aging is an early initiation event and a potential target for extending longevity. We believe that adipose tissues play an essential role in aging and form a potential therapeutic target for the treatment of age-related skin diseases. Further research is needed to improve our understanding of this phenomenon.