What this means
Control cohorts anchor the interpretation of lifespan-extending interventions, yet their lifespans vary even under identical experimental conditions. Without quantifying this expected variation, it is difficult to distinguish unusually short- or long-lived cohorts arising by chance from those reflecting potential experimental anomalies, with important consequences for interpreting treatment effects.
A plain-English summary is on its way. Until then, this is the start of the authors' own summary.
- Who it was tested in
- Not stated
- Kind of research
- Early results, not yet checked by other scientists
The science
- Original title
- A prediction-interval framework for identifying outlier control cohorts in lifespan studies
- Authors
- Maeyens, L. T., Luciano, A., Nelson, J. F. et al.
- Journal
- bioRxiv (preprint, not yet peer reviewed)
- Published
- Oct 22, 2026
- Study type
- Preprint
Abstract
Control cohorts anchor the interpretation of lifespan-extending interventions, yet their lifespans vary even under identical experimental conditions. Without quantifying this expected variation, it is difficult to distinguish unusually short- or long-lived cohorts arising by chance from those reflecting potential experimental anomalies, with important consequences for interpreting treatment effects. The National Institute on Aging Interventions Testing Program (ITP), which tests interventions in mice across three independent sites using standardized protocols, provides a unique opportunity to address this problem. Previously, unusually short-lived males at the University of Texas in 2017 and unusually long-lived females at The Jackson Laboratory in 2022 were identified as potentially anomalous, but no standardized framework existed to determine whether such deviations exceeded expected variation. Here, we analyzed 10,757 control mice spanning 18 years of the ITP to quantify historical variation within and between sites and develop a prediction-interval framework for prospectively identifying unusual cohorts. We found that year-to-year variation, particularly in males, contributed substantially more to variation among cohort means than expected from random sampling alone. Accounting for this variation, our predictive framework flagged the 2022 Jackson Laboratory females but not 2017 University of Texas males, while flagging a previously unrecognized male cohort. Excluding this newly flagged cohort from the original lifespan analysis changed the statistical significance of two rapamycin regimens. These findings highlight the importance of a standardized framework for outlier detection and demonstrate the importance of accounting for natural variability in aging studies.
Maeyens, L. T., Luciano, A., Nelson, J. F. et al. A prediction-interval framework for identifying outlier control cohorts in lifespan studies. bioRxiv. 2026. doi:10.64898/2026.10.21.760720. https://doi.org/10.64898/2026.10.21.760720
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