During FY14 we accomplished the following: 1. We completed additional ITRAK studies with CD4+ T cells from 16 individuals. We found that several mitochondrial proteins were expressed at higher levels in cells from older individuals. Further validation and mitochondrial quantitation is in progress. 2. We carried out studies to investigate the mechanistic basis for elevated NF-κB gene expression signature in CD4+ T cells. We found that a subset of NF-κB target genes were up-regulated in a PI3K-dependent manner, which did not involve mitochondrial reactive oxygen species. These observations provide strong evidence that elevated PI3K activity in CD4+ T cells from older individuals contributes to age-associated chronic inflammation. 3. We established a protocol to separate 10 blood cell types from peripheral blood mononuclear cells for transcription, proteomic and epigenetic analyses. This involved initial separation of CD4+, CD8+, B cells, monocytes and natural killer cells by magnetic beads, followed by flow cytometry. Aliquots of sorted cells were frozen for RNA, proteins and genomic DNA preparation. We have tested and found that good quality RNA and proteins can be prepared from these frozen aliquots.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000386-08
Application #
8931539
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Aging
Department
Type
DUNS #
City
State
Country
Zip Code
Bektas, Arsun; Schurman, Shepherd H; Sen, Ranjan et al. (2017) Human T cell immunosenescence and inflammation in aging. J Leukoc Biol :
Bektas, Arsun; Sen, Ranjan; Ferrucci, Luigi (2016) Does a bit of alcohol turn off inflammation and improve health? Age Ageing :
Bektas, Arsun; Zhang, Yongqing; Lehmann, Elin et al. (2014) Age-associated changes in basal NF-?B function in human CD4+ T lymphocytes via dysregulation of PI3 kinase. Aging (Albany NY) 6:957-74
Bektas, Arsun; Zhang, Yongqing; Wood 3rd, William H et al. (2013) Age-associated alterations in inducible gene transcription in human CD4+ T lymphocytes. Aging (Albany NY) 5:18-36
Munk, Rachel B; Sugiyama, Katsuki; Ghosh, Paritosh et al. (2011) Antigen-independent IFN-? production by human naïve CD4 T cells activated by IL-12 plus IL-18. PLoS One 6:e18553
Kaileh, Mary; Sen, Ranjan (2010) Role of NF-kappaB in the anti-inflammatory effects of tocotrienols. J Am Coll Nutr 29:334S-339S