Nature biotechnologySep 7, 2026

Using protein-based aging measures in a phase 2a clinical trial to support testing of anti-aging treatments

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Updated Sep 9, 2026

Abstract

All six proteomic clocks predicted lower biological age in treated arms of a 12-week trial involving the anti-fibrotic drug rentosertib.

Proteomic clocks may provide valuable biomarkers for aging by tracking immediate biological changes.
The study involved serum proteomes from a published phase 2a trial on idiopathic pulmonary fibrosis.
Pathway analyses suggested potential anti-aging shifts in cellular aging and metabolic processes.
Proteomic clocks cannot distinguish between aging-related effects and disease-specific effects on their own.
Integrating aging endpoints into clinical trials could enhance the evaluation of treatments for specific diseases.

Simplified

Drugs for aging-related diseases may modulate aging itself, but standard clinical trial designs cannot detect such effects. Aging clocks could close this gap, but epigenetic models often yield inconsistent, hard-to-interpret results. In contrast, proteomic clocks, by tracking the immediate effectors of biological change, may excel in providing aging biomarkers or mechanistic insight. Here we compare six proteomic clocks (ProtAge, OrganAge_mortality, OrganAge_chrono, PAC, ipfP3GPT and PAOPAC) on serum proteomes from a published 12-week phase 2a trial of the candidate anti-fibrotic drug rentosertib in idiopathic pulmonary fibrosis. We measure the variance between the clocks and find that all six clocks consistently predicted lower biological age in treated arms. However, proteomic clocks alone cannot deconvolute aging- and disease-specific effects. We addressed this issue indirectly through pathway analyses that identified potential anti-aging shifts in senescence and metabolic processes alongside the anti-fibrotic activity of rentosertib. This work supports the goal of dual-purpose clinical trial designs that integrate aging endpoints into studies for specific disease indications.

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Using protein-based aging measures in a phase 2a clinical trial to support testing of anti-aging treatments

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