A New Preclinical Paradigm for Testing Anti-Aging Therapeutics.
Testing drugs for anti-aging effects has historically been conducted in mouse life-span studies, but are costly and time consuming, and more importantly, difficult to recapitulate in humans. In addition, life-span studies in mice are not well suited to testing drug combinations that target multiple factors involved in aging. Additional paradigms for testing therapeutics aimed at slowing aging are needed. A new paradigm, designated as the Geropathology Grading Platform (GGP), is based on a standardized set of guidelines developed to detect the presence or absence of low-impact histopathological lesions and to determine the level of severity of high-impact lesions in organs from aged mice. The GGP generates a numerical score for each age-related lesion in an organ, summed for total lesions, and averaged over multiple mice to obtain a composite lesion score (CLS). Preliminary studies show that the platform generates CLSs that increase with the age of mice in an organ-dependent manner. The CLSs are sensitive enough to detect changes elicited by interventions that extend mouse life span, and thus help validate the GGP as a novel tool to measure biological aging. While currently optimized for mice, the GGP could be adapted to any preclinical animal model.
Department of Comparative Medicine, University of Washington, Seattle.|Department of Pathology, University of Washington, Seattle.
Warren
W
Ladiges
Department of Comparative Medicine, University of Washington, Seattle.
Jessica M
JM
Snyder
Department of Pathology, University of Michigan, Ann Arbor.
Erby
E
Wilkinson
Department of Veterinary Pathology, UC Davis, California.
Denise M
DM
Imai
Department of Veterinary Pathology, Oklahoma State University, Stillwater.
Tim
T
Snider
Department of Comparative Medicine, University of Washington, Seattle.
Xuan
X
Ge
Department of Rehabilitation Medicine, University of Washington, Seattle.
Marcia
M
Ciol
Department of Comparative Medicine, University of Washington, Seattle.
Christina
C
Pettan-Brewer
Fred Hutchinson Cancer Research Center, Seattle, Washington.
Smitha P S
SPS
Pillai
Department of Comparative Medicine, University of Washington, Seattle.
John
J
Morton
Department of Pathology, University of Washington, Seattle.
Ellen
E
Quarles
Department of Pathology, University of Washington, Seattle.
Peter
P
Rabinovitch
Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, Florida.
Laura
L
Niedernhofer
Department of Comparative Medicine, University of Washington, Seattle.
Denny
D
Liggitt
D026683:Advisory Committees; D000368:Aged; D000375:Aging / Q000187:drug effects* / Q000473:pathology; D000818:Animals; D035843:Biomedical Research; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D010336:Pathology / Q000379:methods; D057170:Translational Research, Biomedical
Aging; Aging lesions in mice; Anti-aging therapeutics; Geropathology Grading Platform; Preclinical drug testing