Early-life nutrition supplementation and epigenetic age in middle-adulthood among Guatemalan adults

Melissa Chapnick ¹, Elaine A Yu ^2,3, Alicia K Smith ^4,5

¹Doctoral Program in Nutrition and Health Sciences, Laney Graduate School, Emory University, Atlanta, GA, USA.
²Vitalant Research Institute, San Francisco, CA, USA.
³Department of Laboratory Medicine, University of California at San Francisco, San Francisco, CA, USA.
⁴Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, USA.
⁵Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
⁶Department of Biostatistics & Bioinformatics, Emory University, Atlanta, GA, USA.
⁷Institute of Nutrition of Central America and Panama (INCAP) Research Center for the Prevention of Chronic Diseases, Institute of Nutrition of Central America and Panama, Guatemala City, Guatemala.
⁸Emory Global Diabetes Research Center, Woodruff Health Sciences Center, Emory University, Atlanta, GA, USA.
⁹Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
¹⁰Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
¹¹Emory Clinical Cardiovascular Research Institute, Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA.

⁰Doctoral Program in Nutrition and Health Sciences, Laney Graduate School, Emory University, Atlanta, GA, USA.

Biorxiv : the Preprint Server for Biology +

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November 19, 2025

View abstract on PubMed

Summary

Early-life nutrition intervention reduced epigenetic aging markers in adulthood. This study highlights the long-term benefits of nutritional support on biological aging.

Area Of Science

Epigenetics and aging research
Nutritional epidemiology
Developmental origins of health and disease

Background

Epigenetic clocks serve as biomarkers for biological aging.
Early-life famine exposure is linked to epigenetic age acceleration.
The long-term effects of early nutrition on epigenetic aging require further investigation.

Purpose Of The Study

To assess the impact of a cluster-randomized early-life nutrition intervention on epigenetic age in adulthood.
To determine if protein-energy supplementation during the first 1,000 days of life influences epigenetic aging markers.

Main Methods

Analysis of follow-up data from the INCAP Nutrition Supplementation Trial in Guatemala.
Measurement of DNA methylation using the Illumina MethylationEPICv2.0 array.
Quantification of epigenetic age using DunedinPACE, PhenoAge, and GrimAge, with acceleration calculated via regression.
Intent-to-treat difference-in-difference modeling to assess intervention effects.

Main Results

Early-life exposure to the 'atole' protein-energy supplement was associated with lower DunedinPACE, PhenoAge acceleration, and GrimAge acceleration.
These associations were observed in middle adulthood among participants exposed during the first 1,000 days of life.
Adjustments for cell type proportions attenuated but did not reverse the direction of these effects.

Conclusions

Early-life nutritional supplementation (first 1,000 days) showed modest reductions in epigenetic age.
Findings support the hypothesis that early nutrition influences biological aging trajectories.
Results align with previous research linking early-life adversity to epigenetic age acceleration.

Keywords:

Epigenetic age aging developmental origins of adult disease

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