Older Mice Heal Skin Injuries More Slowly, but with Less Scarring

Researchers have recently provided evidence for regeneration of skin injuries in old mice to result in lesser degrees of scarring than is the case in young mice. The usual consideration of regeneration with age is that it is disrupted by rising levels of inflammation. Further, the same set of inflammatory mechanisms appear to cause the formation of inappropriate scar-like tissue in organs, the process of fibrosis that contributes to loss of function and organ failure. Finding a way to align those well established results with the data from this study should keep research groups busy for some years. Nothing is simple in mammalian biochemistry.

Organisms repair wounds using a combination of two biological processes: scar formation and tissue regeneration. Scar formation results in deposition of fibrous tissue that disrupts the original tissue architecture. Tissue regeneration results in reconstitution of the original and functional tissue architecture, including all cellular subtypes and absence of scar formation. Although amphibians regenerate lost limbs, mammals generally repair injured tissue with scar formation. However, limited examples of human tissue regeneration do exist, including adult liver regeneration, pediatric traumatic digit tip amputations, and fetal skin wounds. These examples suggest that the mechanisms mediating tissue regeneration remain conserved in mammals.

Human skin wounds invariably form scars. Aging slows the speed of skin re-epithelialization and the subsequent rate of wound repair, but the strength of re-epithelized skin remains roughly the same at any age. Researchers have observed that skin wounds in the elderly close with thinner scars. Indeed, the incidence of keloid and hypertrophic scar formation peaks in the second decade of life and decreases with age. These surprising and somewhat counterintuitive clinical observations suggest that the tissue-regenerative pathway in the skin, instead of being diminished, may be more effective in the elderly. Here we investigated the role of aging as a regulator of mammalian tissue regeneration.

We show that full-thickness skin wounds in aged but not young mice fully regenerate. This aging-induced switch between scar formation and tissue regeneration appears to be a gradual process rather than a binary decision. Exposure of aged animals to blood from young mice by parabiosis counteracts this regenerative capacity. The secreted factor, stromal-derived factor 1 (SDF1), is expressed at higher levels in wounded skin of young mice. Genetic deletion of SDF1 in young skin enhanced tissue regeneration. Our results counter the current dogma that tissue function inevitably worsens with age and uncovers potential mechanisms to explain the paradoxical effect of aging on skin tissue regeneration.

Link: https://doi.org/10.1016/j.celrep.2018.08.054

Comments

Very interesting, and paradoxical. Apparently, scarring from evolutionarily reasoning of is more benefitial than a slower and more complete regeneration. If this discovery gets confirmed, we will have a medical target to reduce scarring after operation or injury in the young. Plastic surgery will embrace the scar suppression too...

It would be ironic if a human manages to love to 150 just to have a perfect regeneration with abysmal chances of survival ;)

Posted by: Cuberat at September 28th, 2018 7:55 AM

Use of silicon scar tape (or any type of prolonged occlusion) prevents keloid formation and reduces scarring considerably; it also reduces the appearance of both large wrinkles and fine lines. The underlying mechanism has not been studied.

Posted by: CD at September 28th, 2018 10:40 AM

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