BACKGROUND: Biological age derived from DNA methylation (mAge) reflects aging-related physiological changes and the risk of age-related diseases. However, the association between oral microbiome and mAge remains unclear.
METHODS: We examined associations between mAge, physical and cognitive function, and the oral microbiome in 311 community-dwelling, predominantly Chinese adults aged 85 years or older. Oral microbial composition was assessed using 16S rRNA sequencing, and mAge was estimated using four established epigenetic clocks: HorvathAge, HannumAge, PhenoAge, and GrimAge.
RESULTS: In this cohort (median chronological age = 88.6 years; median DNA methylation-based biological age = 81.4 years), individuals with lower mAge deviation, corresponding to a younger biological age, exhibit lower oral microbial alpha diversity based on Simpson's index. While no taxa differences reach significance after correction for multiple testing, several short-chain fatty acid-producing genera, such as Prevotella_7 and Veillonella, show nominal associations with both mAge deviation and methylation at aging-related CpG sites, particularly in neurologically relevant genes. Higher abundance of Prevotella_7 species is associated with better cognitive performance (Mini-Mental State Examination), whereas Alloprevotella is linked to poorer cognition.
CONCLUSION: Our findings highlight that, as far as we aware, previously unrecognized oral microbiome composition links to lower mAge deviation and better cognitive function among the oldest-old, suggesting a potential role of the oral microbiome in promoting healthy aging and informing future mechanistic investigations.