Rubedo reports an average 2,1-year decrease in skin “epigenetic age” (estimated from DNA marks) in 11 patients with atopic dermatitis after four weeks of treatment with RLS-1496 cream

Rubedo reports an average 2,1-year decrease in skin “epigenetic age” (estimated from DNA marks) in 11 patients with atopic dermatitis after four weeks of treatment with RLS-1496 cream

Mitra Bio’s clock estimated age from samples of sun-aged skin collected before treatment and on day 36. Some patients showed decreases of up to 8 years. In the patient with the strongest response, the decrease reached 11,7 years on day 63, approximately a month after treatment ended.

On October 12, Rubedo Life Sciences published results from a trial of its cream for atopic dermatitis (eczema), presented on October 2 at the ARDD conference in Boston. The company develops drugs that target pathological senescent cells, which have stopped dividing and can release inflammatory substances.

Chemical marks on DNA change predictably with age. A model trained on these marks, known as an epigenetic clock, uses them to estimate tissue age. According to WIRED, Mitra Bio both developed the clock and analyzed the samples independently of Rubedo. Mitra Bio tested the clock on sun-related skin aging: in 2025, measurements in 75 volunteers put the age of sun-protected skin on the back at 3,8 years younger than skin on the forehead. Rubedo reported as early as March that all participants in its trials apply the cream both to skin affected by disease and to skin showing signs of aging.

RLS-1496 targets GPX4, an enzyme that protects lipids in cell membranes from oxidation. Rubedo’s proposed mechanism is that temporarily inhibiting GPX4 drives pathological senescent cells into ferroptosis, a form of cell death caused by iron-dependent membrane oxidation, while restoring function in neighboring cells that are stressed but have not yet become senescent. In May, Rubedo co-founder Marco Quarta called this approach “senoadaptive”. In April, Jesús Gil’s group at Imperial College London, working independently of Rubedo, reported in Nature Cell Biology that inhibiting GPX4 kills senescent cells through ferroptosis in cell cultures and mice. In culture, these cells contain more iron and oxidants and depend on elevated GPX4 for survival.

In Rubedo’s trial, biopsies showed fewer molecular signs of cellular senescence and inflammation, and microscopic examination of tissue sections showed a 10% increase in type III collagen fibers. According to WIRED, this type of collagen is associated with skin elasticity. The drug was undetectable in the blood of most participants, yet blood levels of inflammatory proteins fell, including CCL22, a protein associated with dermatitis severity. Rubedo believes that targeting GPX4 locally may affect inflammation throughout the body.

In a separate trial for actinic keratosis, precancerous skin patches caused by sun exposure, Rubedo reported that lesion counts fell by an average of 49% over 28 days in 22 patients. In cells without signs of senescence, whose function the drug is intended to restore, the company observed an increase in the protective protein NRF2.

Eric Verdin, president of the Buck Institute for Research on Aging, told WIRED: “I would probably be a little more cautious about what these clocks actually measure, because there are so many of them now.” Anthony Rossi, a dermatologist at Memorial Sloan Kettering Cancer Center, noted: “Some senescent cells are beneficial because they shut down certain processes, such as cancer progression.”

Rubedo CEO Frederick Beddingfield sees potential for a lower-strength version of the drug that could be sold over the counter and compete with retinol. The company plans to begin a phase 2a trial for androgenetic alopecia, hereditary hair loss, in October.