GeroScience Study Links One-Carbon Metabolism Biomarkers to Longitudinal Biological and Epigenetic Aging in Older Indian Adults

A longitudinal study of older adults in India demonstrates that transitions to folate deficiency and persistent hyperhomocysteinemia are directly associated with accelerated biological and epigenetic aging over a 4.5-year period.

Researchers published a study in GeroScience utilizing data from 1,929 participants aged 60 years and older from the Longitudinal Aging Study in India Diagnostic Assessment of Dementia (LASI-DAD).

Over a 4.5-year follow-up, within-person changes in one-carbon (1-C) metabolism biomarkers were tracked alongside clinical biomarker-based Phenotypic Age (in 886 participants) and DNA methylation-based epigenetic clocks (in 583 participants).

Each doubling of blood homocysteine level was longitudinally associated with an estimated 3.17 years of faster Phenotypic Age acceleration, whereas each doubling of folate concentration was associated with a 1.10-year deceleration of biological aging.

Transitioning from normal folate status to folate deficiency was associated with a 2.99-year increase in Phenotypic Age acceleration, alongside significant accelerations in the DunedinPACE (beta = 0.42), DNAm PhenoAge (beta = 0.46), and SystemsAge (beta = 0.71) epigenetic metrics.

Persistent hyperhomocysteinemia over the follow-up period was associated with an additional 2.47 years of accelerated Phenotypic Age compared to those with stable, normal homocysteine levels.

Most existing human cohort research on biological aging clocks has been restricted to high-income populations, leaving aging trajectories in low- and middle-income regions (where nutritional deficits are highly prevalent) poorly understood.

This is the first study to establish that within-person, longitudinal changes in 1-C biomarkers correlate directly with shifts in biological aging speed, moving past traditional cross-sectional association designs.

The diverse responses across different epigenetic measures—with folate showing its most pronounced inverse associations with DunedinPACE and SystemsAge—reinforces that biological aging clocks capture distinct, non-interchangeable physiological domains.

The clear correlation between modifiable nutritional biomarkers and validated biological age metrics supports the integration of metabolic status profiling into patient stratification protocols for longevity trials.

Development pipelines targeting metabolic health may increasingly implement rate-of-aging metrics, such as DunedinPACE, as sensitive and dynamic clinical trial surrogate endpoints.

Large-scale longitudinal cohorts in diverse global regions like India are shown to be essential tools for validating candidate longevity pathways, potentially expanding the geographic reach of translation efforts.

Future clinical trials assessing whether targeted B-vitamin or methyl-donor supplementation can successfully decelerate or reverse epigenetic age acceleration in populations characterized by baseline micronutrient deficiencies.