Characterization of plasma thiol redox potential in a common marmoset model of aging

James R Roede,Karan Uppal,Yongliang Liang,Daniel E.L Promislow,Lynn M Wachtman,Dean P Jones

doi:10.1016/j.redox.2013.06.003

Abstract

Due to its short lifespan, ease of use and age-related pathologies that mirror those observed in humans, the common marmoset (Callithrix jacchus) is poised to become a standard nonhuman primate model of aging. Blood and extracellular fluid possess two major thiol-dependent redox nodes involving cysteine (Cys), cystine (CySS), glutathione (GSH) and glutathione disulfide (GSSG). Alteration in these plasma redox nodes significantly affects cellular physiology, and oxidation of the plasma Cys/CySS redox potential (EhCySS) is associated with aging and disease risk in humans. The purpose of this study was to determine age-related changes in plasma redox metabolites and corresponding redox potentials (Eh) to further validate the marmoset as a nonhuman primate model of aging. We measured plasma thiol redox states in marmosets and used existing human data with multivariate adaptive regression splines (MARS) to model the relationships between age and redox metabolites. A classification accuracy of 70.2% and an AUC of 0.703 were achieved using the MARS model built from the marmoset redox data to classify the human samples as young or old. These results show that common marmosets provide a useful model for thiol redox biology of aging.

Highlights

To gain mechanistic insight into the biomarkers and processes involved in age-related diseases, such as cardiovascular disease, cancer and neurodegenerative diseases like Parkinson′s disease and Alzheimer′s disease, an animal model of aging that exhibits phenotypes similar to the human condition must be developed
Due to phenotypes exhibited by marmosets that represent features present in aging humans [1,15,18], we investigated agerelated changes in plasma redox status in marmosets
Common marmosets (Callithrix jacchus) (72 total animals; 36 male, 36 female) ranging in age from 2–16 years were housed at the New England Primate Research Center and were maintained as described by protocols approved by the Institutional Animal and Use Committee

Summary

Introduction

To gain mechanistic insight into the biomarkers and processes involved in age-related diseases, such as cardiovascular disease, cancer and neurodegenerative diseases like Parkinson′s disease and Alzheimer′s disease, an animal model of aging that exhibits phenotypes similar to the human condition must be developed. The most common nonhuman primate species used in aging research is the relatively large and long-lived rhesus macaque (Macaca mulatta); the size of this species and its long maximum lifespan of 40 years limits the practical use of this model [18]. Adult females give birth to approximately 3–5 offspring per year [1], and similar to humans, marmosets live in compact and stable family groupings. Because of these characteristics, marmosets are perhaps the least expensive primate to maintain in a biomedical laboratory [1]. The short lifespan, small body size, and low zoonotic risk make these primates a desirable model for aging research

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