A recent study has reported that rapamycin, a drug that has long served as an immune suppressor, may also slow aging in human skin.
The small clinical trial found that regular application of rapamycin to the backs of the hands appears to reduce wrinkles and sagging and improve skin tone.
In a recent Geroscience paper, the researchers conclude that rapamycin treatment showed a “clear impact” on skin aging at both the molecular and clinical levels.
The team that led the trial comes from Drexel University College of Medicine in Philadelphia, PA, where senior study author Christian Sell, Ph.D., is an associate professor of biochemistry and molecular biology.
Since discovering rapamycin in the soil of Easter Island half a century ago, scientists have found that the bacterial antifungal compound has many effects in the body.
The drug, which takes its name from Rapa Nui, the native term for the Pacific island, can suppress the immune system and prevent cell replication in mammals.
Rapamycin’s impact on cells
A major mechanism through which rapamycin interacts with cells is the aptly-named mechanistic target of rapamycin (mTOR). Studies have linked the disruption of this pathway to cancer, obesity, and diabetes, as well as genetic and neurological conditions.
An earlier study by Sell and colleagues had demonstrated that rapamycin could improve cell function and slow aging in cultured cells.
Other researchers have also shown that by blocking TOR proteins in yeast cells, rapamycin causes the yeast to grow smaller cells that live longer.
“If you ramp the pathway down, you get a smaller phenotype,” explains Sell.
Scientists have also discovered that rapamycin can slow aging in flies, worms, and mice.
“When you slow growth, you seem to extend lifespan and help the body repair itself – at least in mice,” Sell continues, noting, “This is similar to what is seen in calorie restriction.”
The new investigation, however, is the first to demonstrate an anti-aging effect in living human tissue.
Effects on skin
For the study, which took the form of a clinical trial, the team recruited 13 volunteers who were over 40 years of age.
They asked the participants to apply rapamycin cream to the back of one hand and a placebo cream to the back of the other hand every 1 or 2 days before bedtime.
The participants attended evaluation visits every 2 months for 8 months. During the visits, investigators took photographs to evaluate skin wrinkles and general appearance.
The participants also gave blood samples at the 6-month visit and underwent a skin biopsy of both hands at the 8-month visit.
Tests on the blood samples showed that the rapamycin had not entered the participants’ bloodstream.
At the end of 8 months, most of the hands that had received rapamycin treatment showed an increase in collagen and a reduction in p16 protein.
Collagen is a protein that gives skin its structure, and p16 is a measure of cell senescence, or deterioration through aging. Skin that has more senescent cells is more wrinkled.
Skin that has higher levels of p16 carries a greater risk of infection and also tends to tear more easily and heal more slowly. These are all signs of dermal atrophy, a skin condition that is common in older people.
Investigations of p16 have shown that human cells release the protein as part of a stress response that occurs following cell damage. These studies have also demonstrated that p16 can function as a tumor suppressor, a type of protein that stops cell growth and division happening too fast or in an uncontrolled way.
Cancer develops when cells begin to behave abnormally. This can happen as a result of a mutation that causes cell processes to go awry. As a tumor suppressor, p16 slows down the cell cycle, promoting aging instead of cancer.
“When cells age, they become detrimental and create inflammation,” comments Sell.
“That’s part of aging,” he continues, adding, “These cells that have undergone stress are now pumping out inflammatory markers.”
Chasing the ‘fountain of youth’
The researchers point out that the new findings are just the early stage of their research, and they need to do a lot more before they can say how best to apply rapamycin to delay aging.
They foresee applications that include improving human performance and extending lifespan.
These would require developing a form of the drug that works at much lower doses than those used to prevent organ rejection and treat cancer.
Sell, and another team member are shareholders of a pharmaceutical company that holds the license for the technology, for which there are two patents pending.
“As researchers continue to seek out the elusive ‘fountain of youth’ and ways to live longer, we’re seeing growing potential for the use of this drug.”
Christian Sell, Ph.D.
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