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

Abstract

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.

Quantifying Age-Related Changes in Skin Wound Metabolism UsingIn VivoMultiphoton Microscopy

“…21,23 As aging progresses, intrinsic changes in cell function and metabolism result in dysfunction during the different stages of the healing process. 24 During the inflammatory stage of wound healing, aged macrophages have a decreased phagocytic ability and lower growth factor production compared to young macrophages. 25 Reepithelialization is also delayed as the capacity of keratinocytes and dermal fibroblasts to proliferate and migrate is significantly attenuated with advanced age.…”

Synthetic Retinoid Seletinoid G Improves Skin Barrier Function through Wound Healing and Collagen Realignment in Human Skin Equivalents

“…These changes may be induced by the passage of time (chronological aging) and/or chronic exposure to solar UV irradiation (photo-aging) [17,18], and they result in functional deficits that make the skin more susceptible to injury and can delay or impair the healing process [19]. As a result, older individuals are predisposed to wound infection, trauma and the development of chronic wounds [6]. Thus, efforts to improve wound healing among older individuals can support the structure and function of aged skin and yield anti-aging effects.…”

“…This quantitative tissue monitoring method may be used to evaluate tissue regeneration after skin injury [26,27] and is considered to be a powerful modality for imaging the function and structure of skin tissues during wound healing. We also estimated the effect of seletinoid G on collagen density in UVB-irradiated human skin equivalents by applying second harmonic generation (SHG) imaging, which can be used to provide high-resolution three-dimensional maps of collagen cross-link autofluorescence [6,28]. A previous report showed that seletinoid G increased type I procollagen and reduced matrix metalloproteinase (MMP)-1 expression in skin in vivo [12].…”

“…Aged skin is more prone to injury, and scars formed by aged skin are weaker than those formed by younger skin. Studies on the relationship between aging and wound-healing processes have indicated that the altered mechanical environment of aged skin may largely account for age-related delays in healing [5][6][7].…”

Potential anti‐ageing effect of chondroitin sulphate through skin regeneration

“…We evaluated skin regeneration efficacy of CS using the epidermal skin models. Because of the progressive decrease in the proliferation capacity of keratinocytes during the skin ageing process, the epidermis becomes thinner [23]. Based on this knowledge, we constructed the aged epidermis model to observe the changes in epidermis by CS treatment.…”