The geropathology of organ-specific aging

Abstract

Aging is a complex multidimensional process of progressive decline affecting multiple organ systems by a number of processes that are still not well understood. While many studies have focused on the approach of studying aging across multiple organs, assessment of the contribution of individual organs to overall aging processes is under appreciated. The ability to study and compare organs in the context of organismal aging has been documented recently using a geropathology grading platform in laboratory mice. This concept consists of identifying and grading age-related histologic lesions within organs to generate a quantitative lesion score for each organ, which is representative of the presence and degree of organ-related pathology, and can be compared to scores from other organs examined. This geropathology approach provides a powerful tool to elucidate the basic mechanisms of aging in multiple organs, as well as the response of organs to therapeutic interventions. Furthermore, ongoing work with the concept has expanded and adapted the geropathology grading system to other preclinical animal model species that are commonly used to understand disease associated phenotypes in aging humans, ultimately adding to the utility of the concept.

Keywords: age-related lesions; anti-aging drug responsive organs; geropathology; organ-specific aging.

Figure 1.

A. Composite lesion scores of heart, lungs, liver and kidney from 4 age groups of C57BL/6 and C57BL/6 x BALB/c (CB6F1) male mice show differences in the two strains at the same chronological age points. N=12/cohort. B. Drug response was determined by a significant decrease (P≤0.05) in lesion scores designated by an “X”, compared to non-medicated lesion scores over the course of 3 months in male and female C57BL/6 mice starting at 20 months of age. *For males, as females only showed drug response in the kidney. All mice were obtained from the National Institute on Aging aged rodent colony