The metabolome as a biomarker of mortality risk in the common marmoset

• Type of Material: Article
• Authors: Jessica M. Hoffman, University of Alabama Birmingham; Corinna Ross, Texas A&M University; ViLinh Tran, Emory University; Daniel E.L. Promislow, University of Washington; Suzette Tardif, Texas Biomedical Research Institute; Dean Jones, Emory University
• Language: English
• Date: 2019-02-01
• Publisher: Wiley Inc.
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 Wiley Periodicals, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1002/ajp.22944
• Title of Journal or Parent Work: American Journal of Primatology
• Volume: 81
• Issue: 2
• Start Page: e22944
• End Page: e22944
• Grant/Funding Information: DELP was also supported in part by NIH grant R01 AG049494 and NSF grant DMS1561814, and the University of Washington Nathan Shock Center of Excellence in the Basic Biology of Aging with funding from NIH grant P30 AG013280.; This work was funded in part by NIH 5P51OD011133 to ST, San Antonio Claude D. Pepper Older Americans Independence Center- NIH 5P30AG044271 to ST and NIH AG038746 to DPJ and DELP.
• Keywords: Science & Technology; metabolomics; LIFE-SPAN; sex differences; Zoology; HOMEOSTASIS; Life Sciences & Biomedicine; marmoset; LONGEVITY; longevity; AGE; STRESS; aging
• Research Categories: Biology, Zoology

Abstract

Recently, the common marmoset has been proposed as a non-human primate model of aging. Their short lifespan coupled with pathologies that are similar to humans make them an ideal model to understand the genetic, metabolic, and environmental factors that influence aging and longevity. However, many of the underlying physiological changes that occur with age in the marmoset are unknown. Here, we attempt to determine if individual metabolites are predictive of future death and to recapitulate past metabolomic results after a change in environment (move across the country) was imposed on a colony of marmosets. We first determined that low levels of tryptophan metabolism metabolites were associated with risk of death in a 2-year follow-up in the animals, suggesting these metabolites may be used as future biomarkers of mortality. We also discovered that betaine metabolism and methionine metabolism are associated with aging regardless of environment for the animals, or of metabolomic assay technique. These two metabolic pathways are therefore of particular interest to examine as future targets for health and lifespan extending interventions. Many of the pathways associated with age in our first study of marmoset metabolomics were not found to have significant age effects in our second study, suggesting more work is needed to understand the reproducibility of large scale metabolomic studies in mammalian models. Overall, we were able to show that while several metabolomics markers show promise in understanding health and lifespan relationships with aging, it is possible that choice of technique for assay and reproducibility in these types of studies are still issues that need to be examined further.