Researchers from Johns Hopkins University have published a new study that sheds light on skin rejuvenation, and it shares a link with what some cosmetic companies are doing using laser therapy.
A link between cosmetics and regeneration
During their study, the researchers found that the laser treatments used by cosmetic companies and retinoic acid, which is produced by the skin and sold commercially to treat wrinkles and sun damage, also target the same pathway. In addition, they also found that the activity of this pathway is increased in mice when they regenerate their hair follicles .
Mice are able to regenerate their hair follicles following a deep wound; in humans this does not happen, and the result is a scar and the loss of hair follicles. The researchers discovered that loose pieces of a particular RNA, known as self-noncoding double-stranded RNA (dsRNA) promoted this regeneration in mice. The researchers suggested that dsRNA is secreted by damaged cells at the point of injury and that this spurs the regeneration process.
To support this idea, the researchers investigated if cosmetic skin treatments that damage the skin, such as laser therapy, also involved dsRNA. The research team examined the gene expression profiles of samples following laser therapy, and they found that the genes responsible for sensing dsRNA and the genes responsible for producing retinoic acid in the skin were all being expressed at a higher level.
They also tested human skin cells in vitro, treating them with loose dsRNA in order to emulate the effects of laser therapy, and found that retinoic acid production was increased tenfold in the cells.
Finally, they looked at toll-like receptor 3 (TLR3), a protein that senses dsRNA in both humans and mice. They created TLR3 knockout mice, which were unable to regenerate lost hair follicles following injury. The researchers then gave those mice retinoic acid, and they were once again able to regenerate follicles.
How developmental programs reactivate in regeneration is a fundamental question in biology. We addressed this question through the study of Wound Induced Hair follicle Neogenesis (WIHN), an adult organogenesis model where stem cells regenerate de novo hair follicles following deep wounding. The exact mechanism is uncertain. Here we show that self-noncoding dsRNA activates the anti-viral receptor toll like receptor 3 (TLR3) to induce intrinsic retinoic acid (RA) synthesis in a pattern that predicts new hair follicle formation after wounding in mice. Additionally, in humans, rejuvenation lasers induce gene expression signatures for dsRNA and RA, with measurable increases in intrinsic RA synthesis. These results demonstrate a potent stimulus for RA synthesis by non-coding dsRNA, relevant to their broad functions in development and immunity.
This study suggests that TLR3 is part of a pathway that senses and reacts to the presence of dsRNA by increasing the expression of retinoic acid. It also opens the door for developing therapies to reduce visible skin aging, regenerate lost hair follicles following trauma, and even treat injuries such as burns.
While it may seem somewhat superficial to worry about wrinkles and sun spots on the skin, success in this area could potentially garner greater public support for aging research. After all, seeing is believing to many people, and there could be fewer more visual confirmations than seeing someone’s skin visibly de-aged.
 Kim, D., Chen, R., Sheu, M., Kim, N., Kim, S., Islam, N., … & Son, W. (2019). Noncoding dsRNA induces retinoic acid synthesis to stimulate hair follicle regeneration via TLR3. Nature Communications, 10(1), 2811.