1H-NMR-based metabolomics identifies disrupted betaine metabolism as distinct serum signature of pre-frailty.

Increasing evidence suggests that frailty results from a complex age-associated metabolic decline. Here, we investigated the serum metabolomic profile of a well-characterized cohort of elderly subjects encompassing the whole fit-to-frail continuum. Enrichment analyses revealed a complex dysregulation of amino acids and energy metabolism in both pre-frail and frail participants. Remarkably, upregulated betaine levels emerged as a specific biochemical signature of pre-frail females, holding promise for the development of novel targeted interventions.