Tryptophan metabolism is differently regulated between large and small dogs

• Type of Material: Article
• Authors: Jessica M. Hoffman, University of Alabama Birmingham; J. Veronika Kiklevich, University of Alabama Birmingham; Marika Austad, University of Alabama Birmingham; Tran ViLinh, Emory University; Dean Jones, Emory University; Angela Royal, University of Missouri; Carolyn Henry, University of Missouri; Steven N. Austad, University of Alabama Birmingham
• Language: English
• Date: 2019-11-29
• Publisher: Springer
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2019
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1007/s11357-019-00114-x
• Title of Journal or Parent Work: GeroScience
• Volume: 42
• Issue: 3
• Start Page: 881
• End Page: 896
• Grant/Funding Information: This work was funded by a Glenn/AFAR Postdoctoral Fellowship to JMH and NIH/NIA AG050886 and an award from the Glenn Foundation for Medical Research to SNA
• Keywords: Mouse models; Life Sciences & Biomedicine; Metabolomics; Body size; Geroscience; Tryptophan metabolism; Longevity; Dog; Mitochondrial; Growth; Geriatrics & Gerontology; Life-span; Healthy; Science & Technology; Age; Mortality
• Research Categories: Gerontology; Biology, Veterinary Science; Biology, Animal Physiology

Abstract

Companion dogs have recently been promoted as an animal model for the study of aging due to their similar disease profile to humans, the sophistication of health assessment and disease diagnosis, and the shared environments with their owners. In addition, dogs show an interesting life history trait pattern where smaller individuals are up to two-fold longer lived than their larger counterparts. While some of the mechanisms underlying this size and longevity trade-off are strongly suspected (i.e., growth hormone/IGF-I), there are likely a number of undiscovered mechanisms as well. Accordingly, we have completed a large-scale global metabolomic profiling of dogs encompassing a range of sizes and ages from three cities across the USA. We found a surprisingly strong location signal in the metabolome, stronger in fact than any signal related to age, breed, or sex. However, after controlling for the effects of location, tryptophan metabolism emerged as significantly associated with weight of the dogs, with small dogs having significantly higher levels of tryptophan pathway metabolites. Overall, our results point toward novel, testable hypotheses about the underlying physiological mechanisms that influence size and longevity in the companion dog and suggest that dogs may be useful in sorting out the complexities of the tryptophan metabolic network.