Pilot study of epigenetic aging and treatment response to semaglutide in the SLIM LIVER study.

Michael J Corley, Alina P S Pang, Douglas W Kitch, Amy Kantor, Fred Sattler, Pablo F Belaunzaran-Zamudio, Todd T Brown, Alan Landay, Jordan E Lake, Kristine M Erlandson

University of California San Diego, Department of Medicine, Division of Geriatrics, San Diego, CA, USA. [email protected] of California San Diego, Department of Medicine, Division of Geriatrics, San Diego, CA, USA. [email protected]. · pubmed

Paper

Abstract

Semaglutide, a GLP-1 receptor agonist, improves metabolic health and reduces liver fat in people with HIV (PWH) and metabolic dysfunction-associated steatotic liver disease (MASLD). This post hoc analysis of the 24-week SLIM LIVER single-arm trial (ACTG A5371, No. NCT04216589, registered 02nd Jan 2020) in 41 PWH with MASLD receiving semaglutide (1.0 mg weekly) aimed to evaluate its effect on epigenetic aging and determine whether changes in epigenetic clocks associate with clinical responsiveness. Over 24 weeks, we observed DunedinPACE median change +0.018 (IQR -0.023 to +0.053), PCDNAmTL -0.006 kb (IQR -0.073 to +0.054), and PCGrimAge +0.54 years (IQR -0.33 to +1.26). Participants with decreased DunedinPACE (41.5%) showed greater liver fat reduction (p = 0.024) and trend towards improved gait speed (p = 0.081). Increased PCDNAmTL was associated with better gait speed (p = 0.012). These data suggest early signals of semaglutide responsiveness and relationships to epigenetic age biomarkers. Epigenetic biomarkers may enhance precision in GLP-1RA therapy and enable noninvasive monitoring of biological aging. Trial Registration: ClinicalTrials.gov ID: NCT04216589, registered 02nd Jan 2020.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper suggests that semaglutide treatment may influence epigenetic aging markers in individuals with metabolic dysfunction. This study is relevant as it explores the relationship between a therapeutic intervention and biological aging, potentially contributing to the understanding of aging mechanisms and their modulation.

Author of this paper? Send a correction.