Causal role of microbiome and molecular changes in human aging

Determine whether the multi-omics alterations observed across the transcriptome, metabolome, lipidome, and especially the gut and oral microbiomes in the Human Phenotype Project cohort are causal drivers of human aging or downstream consequences of the aging process.

Background

The paper develops multi-omics aging clocks using transcriptomic, metabolomic, lipidomic, gut microbiome, and oral microbiome data from a large prospective cohort. While these clocks show strong associations with physiological systems, multimorbidity, and disease prevalence, the analyses are primarily cross-sectional.

Given this design, the authors emphasize that their findings demonstrate associations rather than causation. They specifically highlight uncertainty about whether observed molecular and microbiome shifts actively drive aging or are downstream consequences of aging-related physiological changes, underscoring the need for mechanistic studies to establish directionality.