Researchers continue to explore the mechanisms of regeneration in search of both a greater understanding of why it falters in aging, as well as ways to enhance the normal processes of healing. Here they have focused on the role of double-stranded RNA and toll-like receptor 3 in triggering skin regeneration in response to damage:
Researchers have identified a novel cell signaling pathway in mice through which mammals - presumably including people - can regenerate hair follicles and skin while healing from wounds. "Medications that turn on this protein have the powerful potential to decrease scarring as healing of wounds takes place, thereby promoting skin and hair follicle regeneration. A lot of human disability is from scarring. After a heart attack, we're really good at replacing the blood flow, but it's the scar on the heart afterward that's the real problem. We and others in the field of regenerative medicine are interested in how to enhance or trigger regeneration in such situations."
Damaged skin releases double-stranded RNA (dsRNA) - genetic information normally carried by some viruses - that is sensed by a protein called toll-like receptor 3 (TLR3). TLR3, which in other contexts plays a fundamental role in recognizing some disease-causing organisms and activating the immune system, during wounding also activates the genes IL6 and STAT3 to promote hair follicle regeneration. TLR3 also activates other molecules involved in hair development, including the Wnt and Shh signaling pathways and a gene called EDAR, which makes the protein ectodysplasin and plays an important role in skin development.
Researchers compared the protein expression of certain genes in healed wounds in two groups of mice. One group was genetically proficient in wound-induced hair neogenesis, a process in mice and rabbits in which skin and hair follicles regenerate after wounds. The other inbred group of mice was noted to lack this ability. Expression of TLR3 was three times higher in the mice that were better able to regenerate hair. In other experiments, the team found that the expression of TLR3 was five times higher in scratched human skin cell samples compared to healthy skin cell samples, that adding synthetic dsRNA to mouse skin wounds led to a greater number of regenerated follicles, that adding a substance that breaks up dsRNA decreased the number of regenerated follicles, and that regeneration was nearly abolished in mice deficient in TLR3.
It has long been known that skin damage can trigger regeneration. Several cosmetic dermatological procedures, such as chemical peels, dermabrasion and laser treatments, have been used to do that for decades: "One implication from our work is that all of those different rejuvenation techniques are likely working through dsRNA pathways. It may also be that dsRNA could be directly used to stimulate rejuvenation in aging or hair follicle growth in burn patients to regain structures that have been lost."