An experimental drug designed to treat a fatal lung disease may have an unexpected second act: slowing the biological clock.
Insilico Medicine, a Hong Kong-listed biotech company, has published data showing that its AI-discovered drug rentosertib was associated with a reduction in patients' predicted biological age by an average of three to four years, with one aging clock showing a reduction of up to six years. The results, published in Nature Biotechnology, have given the company's co-CEO and founder, Alex Zhavoronkov, a new sense of optimism about the potential of the approach.
"We might have a chance to stop biological aging," Zhavoronkov told Fortune.
What the Study Found
The analysis used serum proteomic profiles from 42 patients who participated in a Phase 2a trial of rentosertib for idiopathic pulmonary fibrosis (IPF), a progressive and often fatal lung disease characterised by scarring of lung tissue. Researchers applied six independently developed proteomic aging clocks, each using different methodologies and training datasets.
Despite their differences, all six clocks showed a consistent trend toward reversed biological age in rentosertib-treated patients compared to the placebo group. The strongest signal was observed at Week 4 in the 30 mg twice-daily group, where some clocks indicated a reduction of approximately three to four years, and up to six years on one measure.
A "Bonus" Effect
Crucially, researchers noted that the dose associated with the strongest anti-aging signal differed from the dose that produced the greatest improvement in lung function. This suggests that the geroprotective activity is at least partially independent of the drug's anti-fibrotic effect, and not merely a downstream consequence of disease improvement.
"There is a promising trend in age reversal in addition to treating the disease, and it came as a bonus for disease treatment," Zhavoronkov told Fox News Digital.
How It Works
Rentosertib is a TNIK (TRAF2- and NCK-interacting protein kinase) inhibitor that Insilico identified through its AI-powered target discovery platform. The protein is implicated in pathways associated with fibrosis, inflammation, and six hallmarks of aging, which is the rationale that originally motivated its development as a dual-purpose therapeutic.
Mechanistically, the study characterised rentosertib as acting as a senomorphic agent, suppressing proteins associated with cellular senescence and downregulating growth-factor signalling pathways linked to accelerated aging. Comparison with 55,319 UK Biobank profiles indicated that rentosertib directly reversed typical age-related protein-expression trajectories.
Caveats and Next Steps
The researchers caution that the findings are preliminary and exploratory. The study involved only 42 patients over a 12-week period, and the clock models were not pre-specified primary endpoints. The changes in proteomic aging measures should not be interpreted as definitive evidence that rentosertib slows chronological aging or extends human lifespan.
The drug has now advanced to a Phase 3 trial in China enrolling over 300 IPF patients. Larger and longer trials, including in healthy adults without IPF, are needed to determine whether the drug truly has anti-aging effects and whether they could lead to better health.
"It's early days. The drug is still investigational," Zhavoronkov told Fox News.