Developmental Metabolic Programming: Early-Life Determinants of Lifelong Health and Disease

Dear Colleagues,

Early life represents a uniquely sensitive window during which environmental exposures can shape long-term metabolic and physiological trajectories. Conditions such as nutrient availability, maternal metabolic status, endocrine signals, oxygenation and paternal contributions do not simply influence development in the short term but can leave lasting biological imprints that affect susceptibility to metabolic, cardiovascular and neurodegenerative diseases.

Emerging evidence indicates that these effects go beyond association. They are driven by coordinated adaptations in cellular metabolism, mitochondrial function, and regulatory networks that can persevere across the lifespan. Despite significant progress, a cohesive mechanistic understanding of how these processes are established and maintained during the life course remains incomplete.

This Special Issue seeks to move beyond descriptive frameworks and advance an integrative, mechanism-oriented view of developmental metabolic programming. A deeper understanding of the molecular, cellular, and systemic processes involved is essential to identify early biomarkers of disease risk and to develop innovative strategies for prevention and intervention.

We welcome contributions that investigate how early-life environmental cues are translated into lasting biological effects through mechanisms such as metabolic flexibility, mitochondrial adaptation, and long-term regulatory remodeling. Special attention will be given to sex-specific differences, early deviations from physiological aging trajectories, and the identification of functionally meaningful biomarkers.

By bringing together molecular, cellular, and translational perspectives, this Special Issue aims to clarify how early-life programming can be leveraged for early risk stratification and targeted intervention, ultimately contributing to improved lifelong health outcomes.

Topics of interest include, but are not limited to:

• Cellular mechanisms linking early-life exposures to long-term metabolic dysfunction;
• Integration of epigenetic and metabolic regulation in long-term phenotypic remodeling;
• Sex-specific programming of metabolic and cardiovascular trajectories;
• Mitochondrial function, bioenergetics, and metabolic flexibility in developmental programming;
• Early-life determinants of cardiac structure, function, and aging;
• Functional biomarkers and early predictors of metabolic risk;
• Interactions between metabolism, redox balance, and inflammatory signaling;
• Human translational models, including fetal-derived cellular systems and cohort-based studies;
• Mechanistic insights from animal models with relevance to human disease;
• Early-life intervention strategies targeting metabolic pathways.

We welcome contributions from researchers across disciplines to advance the understanding of developmental metabolic programming and to identify innovative approaches for prevention, diagnosis, and therapy.

Dr. Susana P. Pereira
Dr. Ludgero C. Tavares
Guest Editors

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• developmental metabolic programming
• in utero programming
• mitochondrial function
• metabolic flexibility
• disease risk
• cardio