Researchers have had enormous success in furthering our understanding of aging through the study of short- lived animal models, including nematode worms, fruit flies, and mice. However, there is a fundamental gap in our knowledge of how well these models can explain aging phenomena in humans. The long-term goal of the work proposed here is to develop a relatively short-lived primate, the common marmoset (Callithrix jacchus), as a powerful model to better understand the biology of aging in humans and non-human primates. The objective of this application is to examine how complex metabolic pathways change with age in marmosets, and to determine how these alterations contribute to longevity and frailty. The central hypothesis of this work is that disruption of co-regulated metabolic modules will progress with aging and will predict age-associated dysfunction and survival. Moreover, dietary restriction, a well-established intervention to delay aging in a variety of species, will prevent or delay degradation of these metabolic relationships and pathways. The rationale for the proposed research is that once we identify metabolic modules that are associated with aging in marmosets, we will be well-positioned to further develop the marmoset as an outstanding aging model and, importantly, to study the proximate molecular factors that determine variation in rates of aging both within and among individuals. The central hypothesis will be tested by pursuing three specific aims: 1) to perform a longitudinal study on the NEPRC common marmoset colony to identify metabolic profiles associated with longevity and functional measures of aging;2) to validate and curate a marmoset metabolomics aging database;and 3) to examine effects of caloric restriction (CR) on metabolic profiles and age-associated dysfunction in marmosets. The work proposed here is innovative, because it develops a novel animal model for aging research, and a novel network approach to study mechanisms of aging in genetically variable populations. Moreover, the interdisciplinary research team created for this project is particularly well suited to bring the work proposed here to fruition. The work proposed here is significant because it will provide the broader research community with a primate model of aging that is more tractable than the existing, longer-lived model systems, and it will introduce a powerful, conceptually novel and easily implemented set of network analysis tools to study the underlying mechanisms of aging in natural populations. Ultimately, this knowledge has the potential to increase understanding of the mechanisms that cause variation in rates of aging among traits within individuals, and among individuals, in human populations.

Public Health Relevance

This project is to develop a relatively short-lived primate, the common marmoset, as a new model to better understand the biology of aging in humans and primates. The study will use detailed chemical and computer- based analyses to analyze how the regulation and function of the body changes with age. The acquired knowledge has the potential to explain causes of variation in traits of aging within individuals and also differences in aging among individuals in human populations.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG038746-03
Application #
8309072
Study Section
Cellular Mechanisms in Aging and Development Study Section (CMAD)
Program Officer
Finkelstein, David B
Project Start
2010-09-30
Project End
2015-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
3
Fiscal Year
2012
Total Cost
$496,052
Indirect Cost
$83,307
Name
Emory University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Go, Young-Mi; Walker, Douglas I; Soltow, Quinlyn A et al. (2015) Metabolome-wide association study of phenylalanine in plasma of common marmosets. Amino Acids 47:589-601
Go, Young-Mi; Kim, Chan Woo; Walker, Douglas I et al. (2015) Disturbed flow induces systemic changes in metabolites in mouse plasma: a metabolomics study using ApoE?/? mice with partial carotid ligation. Am J Physiol Regul Integr Comp Physiol 308:R62-72
Frediani, Jennifer K; Jones, Dean P; Tukvadze, Nestan et al. (2014) Plasma metabolomics in human pulmonary tuberculosis disease: a pilot study. PLoS One 9:e108854
Hoffman, Jessica M; Soltow, Quinlyn A; Li, Shuzhao et al. (2014) Effects of age, sex, and genotype on high-sensitivity metabolomic profiles in the fruit fly, Drosophila melanogaster. Aging Cell 13:596-604
Go, Young-Mi; Jones, Dean P (2014) Redox biology: interface of the exposome with the proteome, epigenome and genome. Redox Biol 2:358-60
Go, Young-Mi; Uppal, Karan; Walker, Douglas I et al. (2014) Mitochondrial metabolomics using high-resolution Fourier-transform mass spectrometry. Methods Mol Biol 1198:43-73
Roback, John D; Josephson, Cassandra D; Waller, Edmund K et al. (2014) Metabolomics of ADSOL (AS-1) red blood cell storage. Transfus Med Rev 28:41-55
Fitzpatrick, Anne M; Park, Youngja; Brown, Lou Ann S et al. (2014) Children with severe asthma have unique oxidative stress-associated metabolomic profiles. J Allergy Clin Immunol 133:258-61.e1-8
Go, Young-Mi; Son, Dong Ju; Park, Heonyong et al. (2014) Disturbed flow enhances inflammatory signaling and atherogenesis by increasing thioredoxin-1 level in endothelial cell nuclei. PLoS One 9:e108346
Paredes, Jamespaul; Jones, Dean P; Wilson, Mark E et al. (2014) Age-related alterations of plasma glutathione and oxidation of redox potentials in chimpanzee (Pan troglodytes) and rhesus monkey (Macaca mulatta). Age (Dordr) 36:719-32

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