A wave of biotech companies is looking to prove that it’s possible to slow down the aging process. Mountain View, California–based Rubedo Life Sciences is starting with the most outwardly visible sign: the skin.
The company’s experimental treatment is showing early promise that it may be able to reduce the appearance of aging, according to data the company presented at the Aging Research and Drug Discovery meeting in Boston earlier this month.
In a small clinical trial, Rubedo tested its topical cream on 11 people with atopic dermatitis, an inflammatory skin condition and the most common type of eczema. The drug targets a mechanism of cellular senescence, a biological state in which damaged or stressed cells permanently stop dividing but do not die. These senescent or “zombie” cells accumulate as people age and can release substances that contribute to inflammation and tissue damage, which contributes to disease.
After four weeks of using the cream, participants lowered the biological age of their skin by about two years, on average. That estimate was based on an aging “clock” designed by a different company, Mitra Bio, which performed an independent analysis on participants’ skin samples. One person in the trial had a reduction of more than 11 years in skin age. Separately, Rubedo found that its treatment was tied to a reduction in inflammation-related markers and a 10 percent increase in a type of collagen associated with skin elasticity and structure.
Biological or epigenetic age is an estimate of how well a person is aging compared to their calendar age. Aging clocks like Mitra’s attempt to calculate this number by looking at patterns of methylations, chemical modifications to DNA that regulate how genes function and can change over time. That metric doesn’t necessarily prove that the body or a particular organ or tissue has become functionally younger, though.
“Our idea is to find ways to change the trajectory of how we age,” says Marco Quarta, Rubedo’s cofounder and chief scientific officer. “Aging is complex. There are many mechanisms, but cellular senescence is one of them.”
Senescent cells are also involved in normal biological processes, such as wound healing and tumor suppression, but their accumulation over time is associated with many age-related conditions. Getting rid of them is one of the leading strategies that anti-aging and longevity companies are pursuing.
Rubedo’s approach aims to clear out senescent cells by targeting a protein known as GPX4, a gatekeeper for cell survival. By transiently turning off GPX4, the drug is designed to make senescent cells more susceptible to ferroptosis, a regulated form of cell death, while reviving stressed, non-senescent cells nearby.
In a separate study, researchers looked at the drug’s effect on actinic keratosis, a skin condition caused by sun damage and produces rough, scaly skin patches and can sometimes progress to skin cancer. In a trial of 18 people, the cream led to a 46 percent reduction in total lesions after a month of use.
Rubedo is studying the same drug for psoriasis and skin with sun damage. Soon, the company will add androgenetic alopecia, a type of hereditary hair loss, to the list. CEO Frederick Beddingfield, previously the chief medical officer at Allergan, where he launched Botox, sees potential in a lower-potency, over-the-counter version for general skin aging, which would compete with retinol. The company is also formulating the drug into a pill to study whether it can be used to treat metabolic conditions associated with aging.
“It's great to see them doing this work,” says Eric Verdin, president and CEO of the Buck Institute for Research on Aging, which has developed several aging clocks. “I would probably be a little circumspect about what these clocks really measure, because right now, there are a proliferation of them.”
Plus, the results that patients will care about is how their skin actually looks and feels, not a result from a biological aging test.
And senescence is just one piece of the aging puzzle, says Anthony Rossi, a dermatologist at Memorial Sloan Kettering Cancer Center. “Some senescent cells are good because they turn things off, like cancer progression.”
He says the science is novel but the work is still very early-stage, and it will be interesting to see how it affects biological aging in people with healthy skin, not just those with certain skin conditions. “The best anti-aging routine right now is sleep, a good diet, and exercise,” he says. For now, at least.