New York, USA, September 7, 2026
Insilico Medicine’s AI-driven investigational drug rentosertib has demonstrated potential to reduce measures of predicted biological age in patients with idiopathic pulmonary fibrosis (IPF), according to new research published in Nature Biotechnology. Researchers analyzed serum proteomic profiles from participants in a Phase 2a clinical trial and applied six independently developed proteomic aging clocks to assess whether treatment was associated with changes in molecular signatures linked to aging. Across the different analytical approaches, rentosertib-treated participants showed a consistent trend toward lower predicted biological age compared with placebo, providing an exploratory indication that the investigational therapy may influence biological processes associated with aging.
Rentosertib Shows Changes Across Six Aging Clocks
The analysis examined serum samples from 42 clinical trial participants and measured approximately 2,841 proteins to characterize treatment-associated changes in the circulating proteome. The researchers applied six proteomic aging clocks, including ProtAge, OrganAge, PAC, ipfP3GPT and PAOPAC, incorporating different methodologies and training datasets. Despite these differences, the clocks showed a broadly consistent direction of change among participants receiving rentosertib. The strongest signal was reported at Week 4 in the 30 mg twice-daily group, where some aging-clock measurements indicated approximately three to four years of predicted biological-age reversal, with one clock showing a reduction of up to six years. The findings were further evaluated against protein-expression profiles from 55,319 UK Biobank participants, providing an external reference for age-associated molecular patterns. The researchers also reported that the observed changes in proteomic aging measures were not simply explained by improvements in respiratory outcomes. The dose associated with the strongest biological-age signal differed from the dose producing the greatest improvement in lung function, suggesting that the molecular changes may not be entirely attributable to improvement in IPF itself. However, the study remains an exploratory analysis, and changes in proteomic aging clocks should not be interpreted as definitive evidence that rentosertib slows chronological aging, extends lifespan or reverses aging-related disease in humans.
AI-Driven Drug Development Targets IPF Biology
Rentosertib, formerly known as ISM001-055 and INS018_055, is an investigational small-molecule therapy developed using Insilico Medicine’s AI-driven drug discovery platform. The candidate targets TNIK (TRAF2 and NCK-interacting protein kinase), a protein implicated in pathways associated with fibrosis and inflammation. Insilico has developed rentosertib as a potential treatment for idiopathic pulmonary fibrosis, a progressive lung disease characterized by scarring of lung tissue and declining respiratory function. The program has become a prominent example of the company’s strategy of combining generative artificial intelligence, target discovery, molecular design and clinical development. The new findings add an additional research dimension to rentosertib’s development by examining whether a candidate initially developed for a specific fibrotic disease may also influence molecular signatures associated with biological aging. This reflects Insilico’s broader interest in geroscience and age-related biology, where researchers are investigating whether therapeutic interventions can modify molecular processes associated with aging alongside treating specific diseases. The proteomic analysis provides a potential framework for assessing these effects within clinical trials rather than relying exclusively on laboratory models.
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Findings Could Expand Rentosertib’s Development Potential
The results could have implications for the future development of rentosertib and for the emerging field of AI-enabled geroscience. Importantly, the study demonstrates the feasibility of incorporating multiple proteomic aging clocks into a clinical development program to generate exploratory measurements of biological age. Such approaches could eventually help researchers investigate whether medicines designed for age-associated diseases also influence broader molecular processes linked to aging. Rentosertib is continuing through clinical development for IPF, and the company has advanced the candidate toward Phase 3 evaluation. Nevertheless, the new Nature Biotechnology findings should be interpreted cautiously. Predicted biological-age changes are biomarker observations rather than proof of aging reversal or increased human longevity, and longer-term clinical studies will be required to determine whether the molecular changes translate into meaningful health outcomes. The research nevertheless highlights how AI-designed medicines and proteomic aging clocks could increasingly intersect in the search for therapies targeting both disease and age-associated biology.
Source: Insilico Medicine press release
