The Geropathology Grading Platform demonstrates that mice null for Cu/Zn-superoxide dismutase show accelerated biological aging

Abstract

The Geropathology Grading Platform (GGP) that is being developed by the Geropathology Research Network provides a grading system that allows investigators to assess biological aging in mice by measuring the pathological status of a wide range of tissues in a standardized scoring system. The GGP is a grading system that generates a numerical score for the total lesions in each tissue, which when averaged over the mice in the cohort provides a composite lesion score (CLS) for each tissue and mouse. In this study, we tested ability of the GGP to predict accelerated aging in mice null for Cu/Zn-superoxide dismutase (Sod1KO mice), which have been shown to have reduced lifespan and healthspan. Using the GGP, we evaluated the pathological status of 11 tissues from male and female wild-type (WT) and Sod1KO mice at 9 to 10 months of age. The whole animal CLS was 2- to 3.5-fold higher for both male and female Sod1KO mice compared to WT mice. The tissues most affected in the Sod1KO mice were the liver, lung, and kidney. These data demonstrate that the GGP is able to predict the accelerated aging phenotype observed in the Sod1KO mice and correlates with the changes in healthspan that have been reported for Sod1KO mice. Thus, the GGP is a new paradigm for evaluating the effect of an intervention on the pathological status of an animal as well as the healthspan of the mice.