Gut microbiome signatures associate with DNA methylation-based biological aging

Multi-institutional collaboration

1. 01

   Models predicting residuals of Horvath, Levine and GrimAge2 clocks showed no predictive signal at species or genus level

2. 02

   The EpiBiome-Accel model for DunedinPACE reached significance at species level (R2 = 0.152) and genus level (R2 = 0.099)

3. 03

   Adding chronological age did not improve performance, indicating age-independence

4. 04

   Bifidobacterium adolescentis was the dominant contributor and strongest predictor of decelerated aging

5. 05

   Succinivibrio dextrinosolvens showed the strongest association with accelerated aging

Study Design

Observational Study

Sample Size

123 subjects

Study Duration

Cross-sectional

Methodology

Paired 16S rRNA gene sequencing and DNA methylation data from 123 monocyte-enriched samples in a cohort including Native Hawaiian and Pacific Islander participants; ElasticNet models with SHAP-based feature attribution and permutation testing.

Limitations

Very small (n=123), single cohort, cross-sectional, monocyte-enriched samples only. Correlational: no causal or interventional data. The authors explicitly frame identified taxa as hypothesis-generating candidates, not individual-level diagnostic markers. Null results for the traditional clocks may reflect low power as much as true absence of signal.