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

Information

  • Research Project
  • 10201488
  • ApplicationId
    10201488
  • Core Project Number
    U19AG057758
  • Full Project Number
    5U19AG057758-04
  • Serial Number
    057758
  • FOA Number
    PAR-16-143
  • Sub Project Id
    5871
  • Project Start Date
    9/30/2018 - 6 years ago
  • Project End Date
    5/31/2023 - 2 years ago
  • Program Officer Name
  • Budget Start Date
    6/1/2021 - 4 years ago
  • Budget End Date
    5/31/2022 - 3 years ago
  • Fiscal Year
    2021
  • Support Year
    04
  • Suffix
  • Award Notice Date
    7/14/2021 - 4 years ago
Organizations

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

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 diet, lack of fetal approaches, and outline the value of our archives now we do not perform euthanasia at the IRG's request. We show how our effect sizes are high and our subject numbers are at the very highest end of any on nonhuman primate providing good significance in the past and ensure robust data.! !

IC Name
NATIONAL INSTITUTE ON AGING
  • Activity
    U19
  • Administering IC
    AG
  • Application Type
    5
  • Direct Cost Amount
    176465
  • Indirect Cost Amount
    29823
  • Total Cost
  • Sub Project Total Cost
    206288
  • ARRA Funded
    False
  • CFDA Code
  • Ed Inst. Type
  • Funding ICs
    NIA:206288\
  • Funding Mechanism
    Non-SBIR/STTR RPGs
  • Study Section
    ZAG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    UNIVERSITY OF WYOMING
  • Organization Department
  • Organization DUNS
    069690956
  • Organization City
    LARAMIE
  • Organization State
    WY
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    820712000
  • Organization District
    UNITED STATES