Scientist finds genetic wrinkle to block sun-induced skin aging
- Date:
- December 16, 2014
- Source:
- University of British Columbia
- Summary:
- Scientists have shown that an enzyme is key in the aging of skin, which is caused mostly by sun exposure; mice lacking that enzyme developed fewer wrinkles, they report. The discovery points toward potential therapies that would preserve the strength of various tissues -- not just skin, but blood vessels and lung passages.
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A scientific team at UBC and Providence Health Care have genetically engineered mice with less wrinkled skin, despite repeated exposure to wrinkle-inducing ultraviolet (UV) light.
The findings, published last week in Aging Cell, raises hope for a drug that would block the activity of Granzyme B in certain places, and thus prevent the aging and deterioration of tissues that depend on collagen -- not just skin, but blood vessels and lung passages.
viDA Therapeutics, a company co-founded by David Granville, a professor in the Department of Pathology and Laboratory Medicine and a principal investigator in the Centre for Heart Lung Innovation of UBC and St. Paul's Hospital, is currently developing a Granzyme-B inhibitor based on technology licensed from UBC. The company plans to test a topically applied drug within two years on people with discoid lupus erythematosus, an autoimmune disease worsened by sunlight that can lead to disfiguring facial scarring. (The musician Seal has such a condition.)
If the drug proves effective in preventing lupus-related skin lesions, there is potential for a cosmetic product to prevent the normal, gradual aging of the skin, which is mostly caused by sun exposure. But the drug might also be used for life-threatening conditions, such as aneurysms and chronic obstructive pulmonary disease, caused by the breakdown of collagen and other proteins that provide structure to blood vessels and lung passages.
Background
A serendipitous discovery: Granville was investigating the role of Granzyme B in atherosclerosis and heart attacks. He and his team wanted to see if the blood vessels of mice lacking Granzyme B were more resistant to hardening and narrowing, which is a major cause of heart attacks in human. In the process, they discovered that such mice retained youthful-looking skin compared to the aged skin on normal mice.
The Canadian Institutes of Health Research (CIHR), Genome BC, and Mitacs financially support this research.
An experimental tanning bed: Granville's team constructed a device to simulate sun exposure on mice. Each mouse was put in a carousel that slowly turned under UV lamps, exposing them for three to four minutes, three times a week -- enough to cause redness, but not to burn. After 20 weeks of repetitive exposure, it became clear that the skin of mice lacking Granzyme B had aged much less -- and their collagen was more intact -- compared to the control groups.
Story Source:
Materials provided by University of British Columbia. Note: Content may be edited for style and length.
Journal Reference:
- Leigh G. Parkinson, Ana Toro, Hongyan Zhao, Keddie Brown, Scott J. Tebbutt, David J. Granville. Granzyme B mediates both direct and indirect cleavage of extracellular matrix in skin after chronic low-dose ultraviolet light irradiation. Aging Cell, 2014; DOI: 10.1111/acel.12298
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