Rapamycin, a drug normally used to prevent organ rejection after transplant surgery, may prove to be the elusive 'fountain of youth' by slowing ageing in human skin, a study claims.
Basic science studies have previously used the drug to slow ageing in mice, flies, and worms. The study, published in the journal Geroscience, is the first to show an effect on ageing in human tissue, specifically skin -- in which signs of ageing were reduced. Changes include decreases in wrinkles, reduced sagging and more even skin tone -- when delivered topically to humans, the researchers said.
"As researchers continue to seek out the elusive 'fountain of youth' and ways to live longer, we're seeing growing potential for use of this drug," said Christian Sell, an associate professor at Drexel University College of Medicine in the US. "So, we said, let's try skin. It's a complex organism with immune, nerve cells, stem cells -- you can learn a lot about the biology of a drug and the ageing process by looking at skin," sell said in a statement.
In the current study, 13 participants over the age of 40 applied rapamycin cream every 1-2 days to one hand and a placebo to the other hand for eight months. The researchers checked on subjects after two, four, six and eight months, including conducting a blood test and a biopsy at the six- or eight-month mark.
After eight months, the majority of the rapamycin hands showed increases in collagen protein, and statistically significant lower levels of p16 protein, a key marker of skin cell ageing. Skin that has lower levels of p16 has fewer senescent cells, which are associated with skin wrinkles. Beyond cosmetic effects, higher levels of p16 can lead to dermal atrophy, a common condition in older people, which is associated with fragile skin that tears easily, slow healing after cuts and increased risk of infection or complications after an injury.
Rapamycin blocks the appropriately named "target of rapamycin" (TOR), a protein that acts as a mediator in metabolism, growth and ageing of human cells. The capability for rapamycin to improve human health beyond outward appearance is further illuminated when looking deeper at p16 protein, which is a stress response that human cells undergo when damaged, but is also a way of preventing cancer.
When cells have a mutation that would have otherwise created a tumour, this response helps prevent the tumour by slowing the cell cycle process. Instead of creating a tumour, it contributes to the ageing process, the researchers explained. "When cells age, they become detrimental and create inflammation. That's part of ageing.
These cells that have undergone stress are now pumping out inflammatory markers," said Sell. In addition to its current use to prevent organ rejection, rapamycin is currently prescribed for a rare lung disease, and as an anti-cancer drug, the researchers said. The study shows a second life for the drug in low doses, including new applications for studying rapamycin to increase human lifespan or improve human performance, the researchers said.
Rapamycin -- first discovered in the 1970s in bacteria found in the soil of Easter Island in the Pacific Ocean -- also reduces stress in the cell by attacking cancer-causing free radicals in the mitochondria.
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