An AI-designed drug for lung disease lowered biological age estimates in four weeks. Digest
AI-designed drugs could open a new path toward treatments that slow or reverse aspects of human aging. Researchers investigated whether rentosertib, developed to treat idiopathic pulmonary fibrosis (a lung-scarring disease), could also affect age-related biological changes.
Researchers analyzed blood samples from 42 adults with an average age of 67 and idiopathic pulmonary fibrosis who completed a randomized, double-blind trial. Participants received rentosertib at 30 mg once daily, 30 mg twice daily, or 60 mg once daily, or placebo, for 12 weeks alongside usual treatment. Six "aging clocks" converted blood-protein patterns at the start and at weeks 2, 4, and 12 into biological age estimates. Four clocks used protein patterns that tend to differ between younger and older people to predict chronological age. The other two based their age estimates on protein patterns associated with a higher or lower risk of death.
- All six clocks showed lower biological-age estimates during rentosertib treatment, while placebo estimates changed little or increased.
- At week 4, age estimates fell by 2.7–3.5 years more with 60 mg once daily than with placebo across the four clocks trained to predict chronological age. Neither of the two clocks trained to predict mortality risk showed a clear effect with this dosing schedule.
- The 30 mg twice-daily dose produced the most consistent reduction in estimated biological age across the different clocks and follow-up visits.
- Age estimates largely plateaued between weeks 4 and 12.
Rentosertib inhibits TNIK, an enzyme involved in several cellular processes, including cell signaling. Analysis of the blood proteins suggested lower activity in several growth-factor and nutrient-sensing pathways after treatment. These signals are essential for normal cell function, but when they remain highly active, they can promote processes linked to aging. Dampening them could therefore help explain the younger age estimates.
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Rentosertib offers an early glimpse of how AI-designed drugs might be used to target human aging and disease. However, in this study, the younger biological age estimates could not distinguish a broader effect on aging from biological changes caused by treating lung fibrosis.