Oral short-chain fatty acid-producing bacteria may be associated with biological age and cognition among the oldest old

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. 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. 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. 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. People’s biological age, which can be estimated from changes to the structure of the molecules inherited from their parents (DNA), often differs from their actual age and reflects how well their body is aging. We studied whether the community of bacteria living in the mouth is linked to biological age and physical as well as brain function in 311 adults aged 85 years or older in Singapore. We found that people who appeared biologically younger tended to have less diverse oral bacteria within their mouths and showed distinct bacterial patterns compared with their peers. Higher amounts of some species, such as Prevotella_7, were linked to better thinking ability. These findings suggest that oral bacteria may influence healthy aging and brain health, offering potential new ways to monitor or support healthy aging through the mouth. Wehnes et al. examine how the oral microbiome is associated with DNA methylation–based biological age and functional health in the oldest old. They find that biologically younger individuals have lower microbial diversity and distinct bacterial patterns related to short-chain fatty-acids and cognition.