Six aging clocks detected younger blood protein profiles in patients taking rentosertib, an experimental drug for idiopathic pulmonary fibrosis. The analysis, published in Nature Biotechnology, suggests that the treatment may affect aging-related biology. It does not establish that patients became younger, regained years of life or will live longer.
Researchers analyzed blood samples from 42 of the 71 participants in a 12-week randomized, double-blind, placebo-controlled trial. The trial tested three regimens: 30 milligrams once daily, 30 milligrams twice daily and 60 milligrams once daily, alongside placebo. The new analysis examined biological markers in those samples, rather than measuring an extension of lifespan.
Rentosertib was developed by longevity biotechnology company Insilico using an AI-based drug discovery platform. It inhibits TNIK, a kinase implicated in several aging-related processes. Its intended target, idiopathic pulmonary fibrosis, is a progressive disease in which excessive scar tissue compromises lung function. Cellular senescence and inflammation are among the aging processes involved in the disease.
What the Aging Clocks Measured
The researchers used six proteomic clocks, which estimate biological age or mortality-related risk from blood protein levels. Four were trained on chronological age and two on mortality. Different teams developed the clocks using UK Biobank data; one was developed by Insilico itself. Unlike a direct measure of health or lifespan, each clock produces an estimate based on its underlying model.
All six clocks detected lower predicted ages with rentosertib, but not at every dose or visit. After four weeks, the four chronological age-based clocks rated patients taking 60 milligrams once daily roughly three years younger, on average, than at the start of treatment. Those changes were statistically significant compared with placebo. The two mortality-trained clocks did not show a significant change at that dose and visit.
The 30-milligram twice-daily group showed the most consistent decreases across both types of clocks. The largest reductions appeared by week four, with little additional change over the remaining eight weeks. As Lifespan News explained in its report on the study, these readings mean that blood protein profiles became more similar to profiles associated with younger people. They are not proof of restored youth.
Why a Fibrosis Protein Matters
Treatment changed the levels of 326 blood proteins, including proteins involved in fibrosis, metabolism and cellular stress responses. Most changes in the two higher-dose groups persisted through the trial or appeared later. This suggests that biological changes continued even after the predicted-age reductions had largely plateaued.
A fibrosis-associated protein called LTBP2 was a major contributor to the younger age estimates. All six aging clocks used it. That shared reliance complicates the interpretation: agreement between the clocks could partly reflect the drug’s effect on fibrosis, rather than a broader slowing of aging.
Changes in predicted age did not closely track changes in lung function. Improved breathing capacity alone therefore might not explain the clock readings, although lung function does not capture every aspect of the disease. The comparison leaves an important question unresolved rather than ruling out disease-specific effects.
Evidence Beyond the Clock Readings
The team also compared treatment-related protein changes with differences between younger and older UK Biobank participants. In the twice-daily group, proteins that tended to be higher in older people decreased, while those that tended to be lower increased. This pattern was not statistically significant in the single daily-dose group.
Proteins associated with cellular senescence tended to increase with placebo and decrease with treatment. That finding suggests reduced senescence-associated activity, but the researchers did not directly measure senescent cells in tissues. A change in associated proteins cannot by itself establish that those cells were removed.
Harvard Medical School professor and study coauthor Vadim Gladyshev told Lifespan News: “This study illustrates how biomarkers of aging can be incorporated into conventional clinical trials.” He added that broader validation could help researchers learn whether treatments influence aspects of aging biology as well as a particular disease.
The findings support further investigation of rentosertib as a potential geroprotector—a compound that might affect aging beyond treating one condition. Fibrosis, metabolism and senescence remain closely connected, however. This small, short analysis cannot separate those effects conclusively, and younger readings from aging clocks should not be presented as evidence that an experimental drug extends human life.
