Pilot study of epigenetic aging and treatment response to semaglutide in the SLIM LIVER study.
Semaglutide isn’t just changing the metabolic game—it might be nudging biological age markers, too. Researchers from UC San Diego, Harvard, and several other big players just dropped data from the SLIM LIVER pilot study, looking at how semaglutide affects epigenetic aging in people with HIV and metabolic dysfunction-associated steatotic liver disease (MASLD).
NPJ Aging
by Corley MJ, Pang APS, Kitch DW et al.
“Pilot study of epigenetic aging and treatment response to semaglutide in the SLIM LIVER study. Corley MJ(1), Pang APS(2), Kitch DW(3), Kantor A(3), Sattler F(4), Belaunzaran-Zamudio PF(5), Brown TT(6), Landay A(7), Lake JE(8), Erlandson KM(9). Author information: (1)University of California San Diego, Department of Medicine, Division of Geriatrics, San Diego, CA, USA. mjcorley@health.ucsd.edu. (2)University of California San Diego, Department of Medicine, Division of Geriatrics, San Diego, CA, USA. (3)Harvard T.H. Chan School of Public Health, Boston, MA, USA. (4)University of Southern California Keck School of Medicine, Los Angeles, CA, USA. (5)National Institute of Allergy and Infectious Diseases (contractor), Rockville, MD, USA. (6)John Hopkins University School of Medicine, Baltimore, MD, USA. (7)University of Texas Medical Branch, Galveston, TX, USA. (8)UTHealth Houston, Department of Medicine, Division of Infectious Diseases, Houston, TX, USA. (9)University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Kristine.erlandson@cuanschutz.edu. 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. © 2026. The Author(s). Conflict of interest statement: Competing interests: M.J.C. serves as a scientific advisor for TruDiagnostic. A.P.S.P. declares no disclosures. K.M.E. has received research funding from the NIH/NIA in support of the present manuscript; outside of the current work, she has received research funding from Gilead Sciences and has consulted for Gilead Sciences, Merck, and ViiV Pharmaceuticals, all paid to her institution. T.T.B. has served as a consultant to Merck, ViiV Healthcare, EMD Serono, and Janssen. P.F.B.-Z. is the Division of AIDS medical officer for the study; however, his views are personal and do not represent the NIH/NIAID’s views.”
Here’s what they did: 41 participants got 1 mg of semaglutide weekly for 24 weeks. The team tracked changes in a set of high-tech epigenetic clocks—DunedinPACE, PCDNAmTL, and PCGrimAge—alongside classic outcomes like liver fat and gait speed.
The results? Not everyone shifted in the same direction, but the signals matter:
41.5% of participants had a drop in DunedinPACE, suggesting slower biological aging. This group also lost more liver fat—clear evidence of a link.
Those with increased PCDNAmTL (a marker for telomere length) moved faster in gait speed tests.
Across the board, changes in these epigenetic clocks tracked with how well participants responded to semaglutide.
Key takeaway: Semaglutide’s benefits might extend well beyond lowering liver fat. Tracking epigenetic age could become a new tool for precision research with GLP-1 receptor agonists. Noninvasive biomarkers like these could make it easier to monitor both peptide effectiveness and aging in real time.
For anyone sourcing GLP-1 research compounds, this study adds even more reasons to keep an eye on semaglutide and its expanding profile. Check the vendor directory for lab-ready options.
Biological age is the next frontier. Peptides like semaglutide are leading the charge.
Related Reading
The STRIDE Trial and Semaglutide: Implications for Clinical Vascular Practice.
News · J Med ChemStructure-Based Adaptation of a SARS-CoV-2 Neutralizing Peptide to New Virus Variants.
News · J Nucl MedCombining an α(v)β(6)-Targeted (177)Lu-Based Peptide Receptor Radionuclide Therapy with Olaparib to Boost Therapeutic Efficacy in Pancreatic Cancer.
For Research Use Only
All content published on Pushing Peptides is intended for educational and informational purposes only. The information provided is not intended as medical advice, diagnosis, or treatment. Peptides discussed in this article are research compounds and are not approved for human therapeutic use by the FDA or any other regulatory agency. All studies referenced involve animal models or in vitro research unless otherwise stated. Consult a qualified healthcare professional before making any decisions related to your health. Pushing Peptides does not sell peptides — we are a vendor directory and educational resource.