Working to Turn Back the Loss of Skin Healing Capacity in Aging
Researchers have been making progress in understanding exactly why skin healing falters with age. Changes in the behavior of sweat glands and surrounding structures built out of keratinocyte cells appear to be important, for example. Skin normally heals through construction of keratinocytes spreading outwards from the sweat glands, but that becomes disrupted in later life. Researchers here fill in more details in the signaling changes involved in that disruption, as well as the role of the immune system, and suggest that it should be possible to nudge the balance of signals back in the right direction. That wouldn't address the root causes of these changes, of course, such as the presence of senescent cells and cross-links in skin tissue, and the age-related decline of the immune system, but might produce enough of a benefit in wound healing to be worth the effort.
Older bodies need longer to mend. Yet until now, researchers have not been able to tease out what age-related changes hinder the body's ability to repair itself. Recent experiments explored this physiological puzzle by examining molecular changes in aging mouse skin. The results delineate a new aspect of how the body heals wounds. "Within days of an injury, skin cells migrate in and close the wound, a process that requires coordination with nearby immune cells. Our experiments have shown that, with aging, disruptions to communication between skin cells and their immune cells slow down this step. Wound healing is one of the most complex processes to occur in the human body. Numerous types of cells, molecular pathways, and signaling systems go to work over timescales that vary from seconds to months. Changes related to aging have been observed in every step of this process."
Both skin cells and immune cells contribute to this elaborate process, which begins with the formation of a scab. New skin cells known as keratinocytes later travel in as a sheet to fill in the wound under the scab. The team focused on this latter step in healing in two-month-old versus 24-month-old mice - roughly equivalent to 20- and 70-year-old humans. They found that among the older mice, keratinocytes were much slower to migrate into the skin gap under the scab, and, as a result, wounds often took days longer to close. Wound healing is known to require specialized immune cells that reside in the skin. The researchers' new experiments showed that following an injury, the keratinocytes at the wound edge talk to these immune cells by producing proteins known as Skints that appear to tell the immune cells to stay around and assist in filling the gap. In older mice, the keratinocytes failed to produce these immune signals.
To see if they could enhance Skint signaling in older skin, the researchers turned to the protein IL-6 that resident immune cells normally release after injury, activating STAT3. When they applied this protein to young and old mouse skin tissue in a petri dish, they saw an increase in keratinocyte migration, which was most pronounced in the older skin. In effect, the old keratinocytes behaved more youthfully. The scientists hope the same principle could be applied to developing treatments for age-related delays in healing. "Our work suggests it may be possible to develop drugs to activate pathways that help aging skin cells to communicate better with their immune cell neighbors, and so boost the signals that normally decline with age."