The Impact of Aging on Skin Healing

Skin heals poorly in old people, the consequence of mechanisms of aging such as the growing number of senescent cells present in aged tissues. Senescent cells are normally generated for a short period of time during wound healing and their pro-growth, pro-inflammatory signals help to coordinate the intricate dance of cell populations involved in regrowth following injury. The constant presence of senescent cells and their signals is disruptive to the healing process, however. As noted in this review paper, a number of other mechanisms are also relevant to the declining capacity for regeneration of skin in older people.

Skin is the human's largest organ and consists of three distinctive layers, the epidermis, dermis, and hypodermis. Skin is equipped with an innate immune response towards tissue injury, with the aim to restore normal tissue structure and function. The normal wound healing process comprises three distinctive stages, inflammation, reepithelialization, and tissue remodelling. The balance between inflammation and its control is essential to maintain a normal wound healing process. This is because acute inflammation at the early stage of wound healing is beneficial in removing cell debris and invading microbes. However, if the inflammation state is prolonged, this will lead to further destruction of adjacent cells and eventually inhibit wound healing.

Aging causes more platelets to adhere to the injured epithelium. This will cause the production of more pro-inflammatory cytokines such as PDGF, TGF-β, and TGF-α. In response to their release, neutrophils will rapidly be recruited to the site of injury. Simultaneously, monocytes will also be recruited to the site of injury. However, since monocytes are larger in size, they require specific adhesion molecules such as ICAM-1 and VCAM-1 to be expressed on the endothelial surface in order to infiltrate the site of injury. In aged skin, these adhesion molecules are greatly reduced, and this impairs the monocyte infiltration.

Reactive oxygen species (ROS) also have an important role in the wound healing process. They are produced by neutrophils and macrophages via NADPH oxidase and help in killing microbes and preventing wound infection. They also have a role as a vasoconstrictor to help reduce blood flow and promote thrombus formation soon after injury. Oxidative stress is also necessary for transition into the proliferative phase. A low amount of ROS provides positive effects on wound healing, whereas prolonged exposure to ROS has a detrimental effect on the wound healing process. Increased production of ROS, such as nitric oxide and superoxide anions, will increase tissue damage and impair healing. In aged skin, more ROS will accumulate due to prolonged inflammation. Hence, this will prolong the state of oxidative stress.

Aged skin will usually have damaged and impaired growth of blood vessels. Once the microcirculation is impaired, there are changes in the inflammatory response due to a reduction in the inflammatory cells and chemical mediators being able to reach the site of injury. On top of that, it also means that there is a relative hypoperfusion at the injury site, leading to less nutrients and oxygen being able to be supplied to support the wound healing process. Temporary hypoxia is important in wound healing process as it can stimulate the release of cytokines and growth factors to induce cell proliferation, migration, as well as angiogenesis. However, a prolonged hypoxia state will negatively affect the wound healing process.


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