Within this program several studies are on-going Role of gut microbiome and type-17 immunity in systemic inflammation of aging. The goal of this project is to define the relationship of type-17 immune cell functions and gut microbiome with systemic inflammation in aging macaques. Identifying the aberrations in gut immune functions and microbiome of aging macaques with higher than baseline inflammation will inform the development of rational intervention strategies toward improving gut immune function and modulating microbiome to target inflammaging. Reports from rodent studies suggests that extended periods of fasting may be an effective intervention to enhance healthspan and extend lifespan, regardless of the composition. However, this recent finding has not been empirically replicated in other models. We are conducting a translational study to evaluate the metabolic effects of a periodic restricted feeding (PRF) schedule in rhesus monkeys. 17alpha-estradiol was tested as an intervention to reverse metabolic decline and pro-inflammatory activity. After establishing an appropriate oral dose for rhesus monkeys, the effects of 12 weeks of treatment were assessed. Glucoregulation and inflammatory measures were collected, and analysis is underway. DNA methylation is now widely used as an indicator of biological age and a marker of to evaluate the effectiveness of age-related interventions. Rhesus monkeys are an important translational model for aging studies with a 93% genetic homology with humans. Characterization of the epigenetic clock representing the lifespan will provide valuable information in an animal model that is widely used in translational aging research. In a cross-sectional approach, we are collecting blood samples from of rhesus monkeys covering the adult lifespan to describe the DNA methylation pattern.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000356-07
Application #
10008621
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2019
Total Cost
Indirect Cost
Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
Zip Code
Gouras, Peter; Brown, Kristy R; Mattison, Julie A et al. (2018) The Ultrastructure, Spatial Distribution, and Osmium Tetroxide Binding of Lipofuscin and Melanosomes in Aging Monkey Retinal Epithelium. Curr Eye Res 43:1019-1023
Maxwell, Nicholas; Castro, Ryan W; Sutherland, Natalia M et al. (2018) ?-Motor neurons are spared from aging while their synaptic inputs degenerate in monkeys and mice. Aging Cell 17:
Mattison, Julie A; Vaughan, Kelli L (2017) An overview of nonhuman primates in aging research. Exp Gerontol 94:41-45
Mercken, Evi M; Capri, Miriam; Carboneau, Bethany A et al. (2017) Conserved and species-specific molecular denominators in mammalian skeletal muscle aging. NPJ Aging Mech Dis 3:8
Vaughan, Kelli L; Mattison, Julie A (2016) Obesity and Aging in Humans and Nonhuman Primates: A Mini-Review. Gerontology 62:611-617
Di Biase, Stefano; Lee, Changhan; Brandhorst, Sebastian et al. (2016) Fasting-Mimicking Diet Reduces HO-1 to Promote T Cell-Mediated Tumor Cytotoxicity. Cancer Cell 30:136-146
Mera, Paula; Laue, Kathrin; Ferron, Mathieu et al. (2016) Osteocalcin Signaling in Myofibers Is Necessary and Sufficient for Optimum Adaptation to Exercise. Cell Metab 23:1078-1092
Abdelmohsen, Kotb; Panda, Amaresh C; De, Supriyo et al. (2015) Circular RNAs in monkey muscle: age-dependent changes. Aging (Albany NY) 7:903-10
Ortega-Molina, Ana; Lopez-Guadamillas, Elena; Mattison, Julie A et al. (2015) Pharmacological inhibition of PI3K reduces adiposity and metabolic syndrome in obese mice and rhesus monkeys. Cell Metab 21:558-70
Lee-Chang, Catalina; Bodogai, Monica; Moritoh, Kanako et al. (2014) Accumulation of 4-1BBL+ B cells in the elderly induces the generation of granzyme-B+ CD8+ T cells with potential antitumor activity. Blood 124:1450-9

Showing the most recent 10 out of 14 publications