# Project 2: Developmental Programming & Aging Interactions in Primate CV Function

> **NIH NIH U19** · UNIVERSITY OF WYOMING · 2021 · $206,288

## Abstract

Project 2: Developmental Programming & Aging Interactions in Primate CV Function
ABSTRACT
Studying aging in baboons can produce useful information to improve our understanding of aging processes in
humans. Systemic cardiovascular (CV) measures, especially cardiac MRI assessments of heart function and
structure, will be evaluated along with heart tissue analyses from our fetal and life course archives and CV
measurements taken on the same animals during regular living situations to evaluate the CV system in the
baboon with aging. The research plan includes studying how stresses on individuals early in life, while still in
the womb, will modify the normal aging of the heart in the long term. This research will be carried out by
characterizing parameters derived from MRI imaging studies (so called imaging biomarkers) and comparing
them with each animal's phenotype, composed of functional, structural and molecular biology measurements,
that can be used to predict aging-related changes. Parameters to be measured in the 96 baboons (6-18 years;
human ~20-70 years) will characterize left and right ventricular function, aortic distensibility, myocardial
extracellular volume, cardiac steatosis, myofilament protein expression, heart rate variability, baroreceptor
response and circulating microRNA's. In all groups, we study equal numbers of males and female. These
measurements will be carried out for all three aims. In Aim 1 normal life course baboons (N=48) will be studied
to establish normative values and serve as age-matched controls for groups studied in subsequent aims. In all
animals, we shall correlate data obtained with microarray data, tissue biopsied and system metabolic data to
MRI measures of myocardial aging changes. In Aim 2 offspring (F1) of mothers, subjected to moderate (30%)
caloric restriction in pregnancy and lactation (N=16), will be studied as well as offspring of obese mothers (OM)
fed a high-fat, high-fructose diet during pregnancy (N=16). Studying baboons with these conditions will help
differentiate changes due to direct effects on myocardial structure and function versus secondary effects on
myocardium due to normal aging. In Aim 3, we shall determine whether the aging trajectory is altered in a
subset (N=16), using cortisol replacement intervention (CRI) challenge. We shall use the same methods on all
animals in all conditions to evaluate changes in cardiovascular function that are attributed to age-related
processes. Importantly, the same animals whose CV parameters are being evaluated in this project (Project 2)
are also being studied across the other projects for neuroendocrine, brain and behavioral function (Project 1),
and metabolic aging (Project 3). Since the 01 submission we can report five papers published on
cardiometabolic effects in the baboon model: three published in J Physiology, one in J Devel Origins Health Dis
and one in Int J Obes (Lond). Response to review: We respond to the major named weaknesses, i.e. the
die...

## Key facts

- **NIH application ID:** 10201488
- **Project number:** 5U19AG057758-04
- **Recipient organization:** UNIVERSITY OF WYOMING
- **Principal Investigator:** GEOFFREY DAVID CLARKE
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $206,288
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201488

## Citation

> US National Institutes of Health, RePORTER application 10201488, Project 2: Developmental Programming & Aging Interactions in Primate CV Function (5U19AG057758-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10201488. Licensed CC0.

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