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🔬TODAY’S BREAKTHROUGH
A new framework, EnsembleAge, improves epigenetic age prediction by combining multiple DNA methylation clocks and benchmarking them against aging, stress, and rejuvenation interventions.
The Discovery:
Built on the MethylGauge dataset of 211 mouse experiments, EnsembleAge integrates multiple regression models to deliver robust, intervention-sensitive biological age estimates. Unlike traditional clocks, it reliably detects both accelerated aging from stressors and deceleration from rejuvenation strategies like caloric restriction or partial reprogramming. A cross-species HumanMouse version extends this to human studies.
The Science:
Problem: Single epigenetic clocks often give inconsistent results across tissues and interventions.
Solution: EnsembleAge aggregates predictions from ridge, lasso, and elastic net models trained on 6,224 DNA methylation samples.
Dynamic version: Adjusts clock composition per dataset to maximize responsiveness, showing highest sensitivity to interventions.
Static version: A fixed elastic net model calibrated on perturbation data for reproducibility and efficiency.
Cross-species clock: HumanMouse EnsembleAge aligns human and mouse methylation data, normalized to maximum species lifespan, enabling translational research.
Performance: EnsembleAge detected rejuvenation from rapamycin and caloric restriction, and stress-induced acceleration in progeria and Huntington’s models, where older clocks failed.
EWAS results: 1,291 CpG sites linked to age acceleration were enriched in promoter and CpG island regions tied to survival and lifespan regulation.
Your Action:
When reading about anti-aging interventions tested with epigenetic clocks, check whether they used ensemble or validated models. These reduce false signals and improve reliability.
For now, continue supporting longevity with evidence-based habits: exercise, sleep, and nutrient-rich diet.
Bottom Line:
By integrating multiple models and benchmarking against interventions, EnsembleAge sets a new standard for reliable biological age measurement.
Source:
EnsembleAge: enhancing epigenetic age assessment with a multi-clock framework. GeroScienceme. Haghani A, Horvath S, et al.
https://doi.org/10.1007/s11357-025-01808-1
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