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'One of those moments that we live for in science': UBC researchers may have stumbled upon the secret to youthful skin

Mice without a certain enzyme didn’t appear to age

Scientists at the University of B.C. searching for ways to slow the deterioration of blood vessels may have stumbled on to the key to youthful skin.

While exploring the effects of the protein-degrading enzyme Granzyme B on blood vessels during heart attacks, professor David Granville couldn’t help noticing that mice engineered to lack the enzyme had beautiful skin at the end of the experiment, while normal mice showed signs of age.

“This is one of those moments that we live for in science,” said Granville, a researcher for Providence Health Care.

“We were interested in the effects of aging on blood vessels; we had no idea (the absence of this enzyme) would have any effect on their skin.”

The discovery pushed Granville’s research in an unexpected new direction.

The researchers built a mechanized rodent tanning salon and exposed mice engineered to lack the enzyme and normal mice to UV light three times a week for 20 weeks, enough to cause redness, but not to burn.

At the end of the experiment, the engineered mice still had smooth, unblemished skin, while the normal mice were deeply wrinkled.

“About 80 to 90 per cent of visible skin aging is caused by sunlight,” said Granville. “We found that by knocking out this gene we could markedly protect against the loss of collagen and it prevented wrinkling in these mice.”

Granzyme B breaks down proteins and interferes with the organization and the integrity of collagen, dismantling the scaffolding — or extra-cellular matrix — that cells bind to. This causes structural weakness, leading to wrinkles.

Sunlight appears to increase levels of the enzyme and accelerate its damaging effects.

Granville envisions cosmetic uses for his discovery in the prevention and repair of sun-damaged skin.

“We have generated natural and synthetic inhibitors of this enzyme, and one can easily see the application for this after excessive sun exposure ... or in other cosmetics as well,” he said. “That’s obviously the first thing that comes to mind.”

Many anti-aging cosmetics apply collagen to the skin, which does nothing to halt the mechanisms of aging.

“By adding collagen without putting out the fire, you are just adding wood to the fire,” he said.

“This offers an actual realistic solution, where you can inhibit the enzyme that is leading to the breakdown of collagen.”

Drugs that can block the activity of Granzyme B could also have valuable medical applications.

“We are developing inhibitors that can prevent the activity of Granzyme B and prevent the degradation of that so-called extra-cellular matrix,” said Granville.

A firm called viDa Therapeutics — co-founded by Granville — is already working on a lotion they hope will prevent sores, inflammation and facial scarring caused by sunlight in people with a form of lupus, an autoimmune skin disease. .

Granville is also continuing to examine the effects of Granzyme B on aneurysms, especially of the aorta, the largest blood vessel in the human body.

“When we inhibit Granzyme B in that model we can affect the collagen organization and strength of collagen in the aorta and prevent rupturing,” he said.

The research is funded by Canadian Institutes for Health Research and Genome BC.