Organ transplant drug rapamycin may slow skin aging, new study finds

Since time immemorial, humankind has been fascinated with discovering the elixir of youth. But, vanity is not the only driving force in the race to delay senescence. Aging is a major risk factor for many of the most common and debilitating diseases that affect us. Cancer, dementia, and cardiovascular disease are all more common in older individuals. One of the first organs in the body to show signs of aging is the skin. Signs of skin aging include fine lines, wrinkles, sagging, and loss of volume and elasticity. These changes are caused photodamage due to sun exposure and dermal atrophy (decrease in skin thickness) due to collagen loss. There is no shortage of creams, lotions, supplements, and serums on supermarket shelves that promise youthful skin. Yet, the search for the elusive fountain of youth continues. Research on potential antiaging interventions has exploded in the last decade or so. One of the most promising findings is rapamycin, an FDA-approved drug that is used to prevent organ rejection in transplant recipients. “We’re seeing growing potential for the use of this drug,” says Christian Sell, PhD, of the Department of Biochemistry and Molecular Biology at Philadelphia’s Drexel College of Medicine, where a study on the effects of rapamycin cream on skin aging was conducted. The Drexel study enrolled a total of 13 participants, all over the age of 40, who were given rapamycin cream to apply to the back of one hand every 1-2 days for a period of 8 months. For the sake of comparison, the subjects were also given a placebo (a cream with no therapeutic value) in an identical container to apply to the other hand. The scientists conducted periodic checks at 2, 4, 6, and 8 months with blood tests and skin biopsies 6 and 8 months after the study began. At the conclusion of the study, the subjects’ skin was evaluated for signs of aging, such as fine wrinkles and pigmentation, using standardized scales. The researchers also measured levels of a protein called p16, which is a key marker of skin senescence. Human skin with lower levels of p16 has fewer senescent cells and wrinkles. On the other hand, skin with higher levels of p16 exhibits thinning, fragility, delayed healing, and increased risk of infection. The researchers published their results in the scientific journal GeroScience. They found that skin which was treated with rapamycin showed improvement in the signs of photoaging, including a decrease in fine lines, sagging, and prominence of veins and tendons. The rapamycin-treated skin also had increased volume due to increase in collagen. The treated areas had a brighter, more even skin tone. The changes became evident after about 4 months of rapamycin application, with continued improvement at subsequent checks. What’s interesting is that a very low dose of the drug was applied to the hands during the study. Blood tests confirmed that the rapamycin was not absorbed into the subjects’ bloodstream. So, how does rapamycin accomplish these amazing results? The study authors say the drug targets a protein called mTOR (mechanistic target of rapamycin), which is a critical mediator in cell growth and aging. By blocking the mTOR protein, rapamycin leads to a reduction in the number of aging skin cells. Interestingly, rapamycin has other benefits. Aging cells are prone to inflammation. An inflammatory environment in the body promotes tumor formation. Rapamycin reduces inflammation. Moreover, cancer cells multiply at a much faster rate than normal cells. To meet the high energy demands of rapid multiplication, cancer cells rely on nutrient uptake and metabolism, which are controlled by mTOR. By reducing inflammation and blocking mTOR, rapamycin could, in theory at least, lower the chances of developing skin cancer. Rapamycin was first discovered in the 1970s on Rapa Nui (Easter Island) in bacteria from a soil sample and was first approved by the FDA in 1999. In addition to its use to prevent organ rejection, it is used to treat lymphangioleiomyomatosis, a rare lung disease, tuberous sclerosis complex, a genetic disease in which non-cancerous tumors grow in multiple vital organs, as well as some neurological diseases. The Drexel study findings are encouraging, but the researchers warn that it is early days yet. Many more questions remain to be answered about how to safely and effectively harness the antiaging effects of rapamycin. Further studies are needed to test the drug in clinical settings and there are many regulatory hurdles before rapamycin cream becomes widely available as a prescription or over-the-counter antiaging product.