Document Type

Article

Publication Date

1-14-2025

Publication Title

Geroscience

Keywords

JGM

JAX Source

Geroscience.

ISSN

2509-2723

PMID

39806236

DOI

https://doi.org/10.1007/s11357-024-01480-x

Grant

This work was supported by the National Institutes of Health: The Jackson Laboratory Nathan Shock Center of Excel- lence in the Basic Biology of Aging (5P30AG038070), The San Antonio Nathan Shock Center of Excellence in the Basic Biol- ogy of Aging (5P30AG013319), The Center for Testing Potential Anti-Aging Interventions (5U01AG022307), and Interventions That Retard Mammalian Aging (U01AG022308). This work was also supported by Calico Life Sciences LLC (Dietary Interven- tion of Aging in Genetically Diverse Mice, sponsored research funding number CALICO-GAC-06).

Abstract

Analysis of preclinical lifespan studies often assume that outcome data from co-housed animals are independent. In practice, treatments, such as controlled feeding or putative life-extending compounds, are applied to whole housing units, and as a result, the outcomes are potentially correlated within housing units. We consider intra-class (here, intra-cage) correlation in three published and two unpublished lifespan studies of aged mice encompassing more than 20,000 observations. We show that the independence assumption underlying common analytic techniques does not hold in these data, particularly for traits associated with frailty. We describe and demonstrate various analytical tools available to accommodate this study design and highlight a limitation of standard variance components models (i.e., linear mixed models) which are the usual statistical tools for handling correlated errors. Through simulations, we examine the statistical biases resulting from intra-cage correlations with similar magnitudes as observed in these case studies and discuss implications for power and reproducibility.

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