Skin Structure–Function Relationships and the Wound Healing Response to Intrinsic Aging

Significance: Chronic wounds, such as diabetic foot ulcers, venous stasis ulcers, and pressure ulcers affect millions of Americans each year, and disproportionately afflict our increasingly older population. Older individuals are predisposed to wound infection, repeated trauma, and the development of chronic wounds. However, a complete understanding of how the attributes of aging skin affect the wound healing process has remained elusive. Recent Advances: A variety of studies have demonstrated that the dermal matrix becomes thinner, increasingly crosslinked, and fragmented with advanced age. These structural changes, as well as an increase in cell senescence, result in altered collagen fiber remodeling and increased stiffness. Studies combining mechanical testing with advanced imaging techniques are providing new insights into the relationships between these age-related changes. Emerging research into the mechanobiology of aging and the wound healing process indicate that the altered mechanical environment of aged skin may have a significant effect on age-related delays in healing. Critical Issues: The interpretation and synthesis of clinical studies is confounded by the effects of common comorbidities that also contribute to the development of chronic wounds. A lack of quantitative biomarkers of wound healing and age-related changes makes understanding structure-function relationships during the wound healing process challenging. Future Directions: Additional work is needed to establish quantitative and mechanistic relationships among age-related changes in the skin microstructure, mechanical function, and the cellular responses to wound healing.