Abstract
During aging, the skin undergoes changes in architecture and composition. Skin aging phenotypes occur due to accumulated changes in the genome/epigenome, cytokine/cell adhesion, cell distribution/extracellular matrix (ECM), etc. Here we review data suggesting that tissue mechanics also plays a role in skin aging. While mouse and human skin share some similarities, their skin architectures differ in some respects. However, we use recent research in haired murine skin because of the available experimental data. Skin suffers from changes in both its appendages and inter-appendage regions. The elderly exhibit wrinkles and loose dermis and are more likely to suffer from wounds and superficial abrasions with poor healing. They also have a reduction in the number of skin appendages. While telogen is prolonged in aging murine skin, hair follicle stem cells can be rejuvenated to enter anagen if transplanted to a young skin environment. We highlight recent single-cell analyses performed on epidermis and aging human skin which identified new basal cell subpopulations that shift in response to wounding. This may be due to alterations of basement membrane stiffness which would change tissue mechanics in aging skin, leading to altered homeostatic dynamics. We propose that the extracellular matrix (ECM) may play a key role as a chemo-mechanical integrator of the multi-layered senescence-associated signaling pathways, dictating the tissue mechanical landscape of niche microenvironments in aging phenotypes. We show examples where failed chemo-mechanical signaling leads to deteriorating homeostasis during skin aging and suggest potential therapeutic strategies to guide future research to delay the aging processes.
Highlights
As skin ages, it undergoes physiological and pathological changes causing a decline in both structure and function (Gilchrest, 1989; Tobin, 2017)
We review the physiological changes associated with skin aging (Table 1 and Figure 1C) and highlight the potential role of tensional homeostasis
Utilizing and providing a chemically or mechanically induced young environment might rescue aging phenotypes in the skin. This approach could potentially rescue basal layer homeostasis to control (1) epidermal thickness, (2) wound healing, (3) activation of HFSC, and (4) cell reprogramming during wound-induced hair neogenesis (Bhoopalam et al, 2020)
Summary
It undergoes physiological and pathological changes causing a decline in both structure and function (Gilchrest, 1989; Tobin, 2017). Aging skin is characterized by reduced ECM deposition brought about by (1) low skin tension, (2) dampened cellular responses to mechanical stimuli coupled with (3) low pro-inflammatory signaling, and (4) the reduced capacity of dermal adipocytes to transdifferentiate into myofibroblasts (Varani et al, 2006; Zhang et al, 2019) which could underlie reduced scarring after wounding. The counterbalance between Wnt and BMP-2; second, M2 subtype macrophage polarization; third, growth factor secretion, especially HGF and IGF-1 (Chu et al, 2019) This mechanical activation of hair cells seems compromised in the stiff and less extendable aged mice skin (Lynch et al, 2017; Meador et al, 2020) which has difficulty in eliciting a desirable regeneration response via stretching. Subcutaneous injection of ADSC significantly increased collagen density, dermal thickness, and fibroblast number in hairless mice (Fukuoka et al, 2017), and stimulated collagen synthesis of human dermal fibroblasts (Kim et al, 2009)
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