A new study published in the scientific journal Nature has found that women’s and men’s skin renews through different mechanisms. Researchers from the Université libre de Bruxelles (ULB) and the University of Cambridge discovered that skin stem cells in females act in a much more coordinated manner than those in males. This difference, driven by sex hormones, also contributes to faster wound healing.
For a long time, biological differences between the sexes were thought to be largely confined to the reproductive organs. However, the new study shows that sex influences even the skin. The scientists used a specialized microscopy technique to continuously observe skin stem cells and their “descendants” in laboratory mice over an unprecedented period of five months. They subsequently verified the mechanism using a laboratory model of human skin.
The skin’s outer layer is constantly renewed. Stem cells are located in its deepest layer, where they multiply. Some newly formed cells remain stem cells, while others become specialized cells through a process known as differentiation, which helps maintain the skin’s barrier function. These specialized cells move toward the surface and eventually shed. Five months of observation revealed that stem cells do not transform directly into mature cells. Instead, they first pass through an intermediate stage during which their ability to divide is limited.
Even more unexpectedly, the researchers found that in females, the two “daughter” cells produced by a single cell division make decisions synchronously. They either divide again at the same time or undergo specialization simultaneously. In males, by contrast, each cell behaves more independently and follows its own rhythm.
“Initially, we wanted to understand how the skin renews itself and whether there is a hierarchy at the top of which stem cells sit. We were also surprised to discover such pronounced differences between the mechanisms of skin renewal in females and males,” explains the study’s first author, Dr. Dan Engelman.
To determine the cause of these differences, the scientists investigated the role of sex hormones. Experiments in laboratory animals showed that removing the main source of testosterone causes the skin to begin behaving more like female skin, while administering the active form of testosterone, dihydrotestosterone, restores the original state. Conversely, removing the ovaries reduces stem cell proliferation and almost completely eliminates coordination between cells. However, treatment with the female hormone estradiol reverses this effect.
Put simply, testosterone, which is present at higher levels in males, regulates the rate at which skin cells mature, while estrogens promote stem cell proliferation and coordinated activity in females. Notably, testosterone also accelerated stem cell differentiation in laboratory-reconstructed human skin, confirming that a similar mechanism operates in humans.
The researchers also observed that, thanks to the early activation of stem cells and their synchronized activity under the influence of female sex hormones, wounds heal considerably faster in females, particularly during the first few days. Doctors have long observed differences between females and males in wound healing, the severity of inflammatory diseases, and the incidence of certain skin cancers. However, the precise biological reasons for these differences had remained unknown.
“This study represents a major technological achievement, while the differences discovered between male and female skin stem cells are astonishing and entirely unexpected. It sheds light on numerous clinical observations that previously had no biological explanation,” says the study’s senior author, Professor Cédric Blanpain.
He also notes that “sex is a parameter that is often overlooked in biology and medicine.” The researchers plan to investigate in greater detail how skin cancers develop and progress differently in females and males. In the longer term, the findings could pave the way for personalized treatments tailored to a patient’s sex, including therapies for burns, postoperative recovery, and chronic ulcers in people with diabetes.
