These cross-section images show three-dimensional human skin models made of living skin cells. Untreated model skin (left panel) shows a thinner dermis layer (black arrow) compared with model skin treated with the antioxidant methylene blue (right panel). [Zheng-Mei Xiong/University of Maryland]
These cross-section images show three-dimensional human skin models made of living skin cells. Untreated model skin (left panel) shows a thinner dermis layer (black arrow) compared with model skin treated with the antioxidant methylene blue (right panel). [Zheng-Mei Xiong/University of Maryland]

Cosmetic products have offered the promise of younger and more youthful looking skin for centuries, yet few, if any, deliver on such a promise. However now, new data from a team of University of Maryland investigators suggests that the thiazine dye methylene blue, which has been used medicinally, may also slow the aging of human skin. Findings from the new study were published recently in Scientific Reports in an article entitled “Anti-Aging Potentials of Methylene Blue for Human Skin Longevity.”

The UMD team tested the methylene blue for 4 weeks in skin cells from healthy middle-aged donors, as well as those diagnosed with progeria—a rare genetic disease that mimics the normal aging process at an accelerated rate. In addition to methylene blue, the researchers also tested three other known antioxidants: N-acetyl-L-cysteine (NAC), MitoQ, and MitoTEMPO (mTEM).

“Our work suggests that methylene blue could be a powerful antioxidant for use in skin care products,” explained senior study investigator Kan Cao, Ph.D., associate professor of cell biology and molecular genetics at UMD. “The effects we are seeing are not temporary. Methylene blue appears to make fundamental, long-term changes to skin cells.”

In the current study, methylene blue outperformed the other three antioxidants, improving several age-related symptoms in cells from both healthy donors and progeria patients. The skin cells—fibroblasts that produce the structural protein collagen—experienced a decrease in damaging molecules known as reactive oxygen species (ROS), a reduced rate of cell death, and an increase in the rate of cell division throughout the 4-week treatment.

Interestingly, the researchers also tested methylene blue in fibroblasts from older donors (>80 years old) for a period of 4 weeks. At the end of the treatment, the cells from older donors had experienced a range of improvements, including decreased expression of two genes commonly used as indicators of cellular aging: senescence-associated β-galactosidase and p16.  

“I was encouraged and excited to see skin fibroblasts, derived from individuals more than 80 years old, grow much better in methylene blue-containing medium with reduced cellular senescence markers,” noted lead study investigator Zheng-Mei Xiong, Ph.D., assistant research professor of cell biology and molecular genetics at UMD. “Methylene blue demonstrates a great potential to delay skin aging for all ages.”

To take their results one step further, the UMD team used the simulated human skin to perform several more experiments. This simulated skin—a 3D model made of living skin cells—includes all the major layers and structures of skin tissue, with the exception of hair follicles and sweat glands.

“This system allowed us to test a range of aging symptoms that we can't replicate in cultured cells alone,” Dr. Cao noted. “Most surprisingly, we saw that model skin treated with methylene blue retained more water and increased in thickness—both of which are features typical of younger skin.”

Additionally, the investigators used the model skin to test the safety of cosmetic creams with methylene blue added. The results suggested that methylene blue causes little to no irritation, even at high concentrations. Encouraged by these results, the research team hopes to develop safe and effective ways for consumers to benefit from the properties of methylene blue.

“We have already begun formulating cosmetics that contain methylene blue. Now we are looking to translate this into marketable products,” Dr. Cao concluded. “We are also very excited to develop this three-dimensional skin model system. Perhaps down the road, we can customize the system with bioprinting, such that we might be able to use a patient's own cells to provide a tailor-made testing platform specific to their needs.”