Abstract

. In aging, immune systems falter and the elderly are more susceptible to infection. Age related changes include decreased T-cell activation/proliferation, decreased production of IL-2 and decreased expression of IL-2R1. These are the same key immune changes that are seen in returning astronauts who have experienced altered immune function and increased vulnerability to infection during spaceflights. Loss of immune response in aging and spaceflight has been previously identified in T cells. We have previously identified microgravity induced changes in gene expression, promoter regions, transcription factors and signal transduction pathways in human CD4+ T-cells under normal and altered gravity conditions. Our preliminary data from International Space Station (ISS) described within this proposal show that in early T-cell activation at least one miRNA was upregulated during activation in normal gravity (g), while in microgravity ( The Specific Aims are the following: (1) Identify gene expression of miRNAs during T-cell activation (using arrays and qRTPCR) under normal gravity. (2) Identify the MiRNA(s) target genes using bioinformatics and verify the changes in expression of those targets messages (qRTPCR). We will test the ability of microgravity to induce/reduce expression of MiRNAs and their targets and verify these results using miRNA overexpression viral constructs or dsRNA. (3) Analyze the protein synthesis of the upregulated/downregulated target genes (SDS PAGE gels and Western Blot proteomics) that are affected by T-cell activation under normal gravity and microgravity conditions. (4) Compare the expression of key MiRNAs candidates and genes after activation in normal gravity and microgravity, vs. that of the lymphocytes from an older population.

Public Health Relevance

Identifying altered microRNAs and their targets in T-cells that have suppressed immune response in spaceflight but normal expression in 1g flight controls will contribute to our understanding of aging and will likely reveal important causes of immunosuppression in the elderly. In recent ISS experiments, one MiRNA is significantly downregulated in

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Exploratory/Developmental Cooperative Agreement Phase I (UH2)
Project #
1UH2AG037628-01
Application #
7945885
Study Section
Special Emphasis Panel (ZEB1-OSR-E (M1))
Program Officer
Fuldner, Rebecca A
Project Start
2010-09-01
Project End
2012-08-31
Budget Start
2010-09-01
Budget End
2011-08-31
Support Year
1
Fiscal Year
2010
Total Cost
$170,337
Indirect Cost

  Institution

Name
Northern California Institute Research & Education
Department
Type
DUNS #
613338789
City
San Francisco
State
CA
Country
United States
Zip Code
94121

  Publications

Grenon, S Marlene; Jeanne, Marion; Aguado-Zuniga, Jesus et al. (2013) Effects of gravitational mechanical unloading in endothelial cells: association between caveolins, inflammation and adhesion molecules. Sci Rep 3:1494
Grenon, S Marlene; Owens, Christopher D; Alley, Hugh et al. (2013) n-3 Polyunsaturated fatty acids supplementation in peripheral artery disease: the OMEGA-PAD trial. Vasc Med 18:263-74