Fig. 1: Cutaneous changes in the aged hypodermis.

Aging in the hypodermis not only contributes to skin thinning and sagging but also considerably harms the dermal microenvironment and skin function. Aged ASCs exhibit senescent characteristics including reduced viability and proliferation, while the individual morphology and phenotype are independent on donor age. Accumulated oxidative stress during aging reduces the expression of stemness markers and interferes with mitochondrial function and autophagy progression. The immature fibroblast–adipocyte lineage loses its adipogenic-antimicrobial properties with a strengthening of the myofibroblast phenotype and no longer produce antimicrobial peptide in adulthood. Aged immune cells lose their ability to sustain adipose tissue homeostasis and promote healthy aging in various ways. BAT-mediated thermogenesis also declines with age. The aged microenvironment induces an age-dependent increase in the expression of pro-inflammatory mediators and a more proinflammatory M1-like phenotype of macrophages in the hypodermis. Systemic differences in the quantity, intensity, pathway, and signaling mediators of cell–cell communication in young and aged skin have been observed.