Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination

• DOI: 10.18632/aging.100720
• Publication Date: 2016-03-06T04:42:24Z
• Authors: Juilee Thakar; Subhasis Mohanty; A. Phillip West; Samit R. Joshi; Ikuyo Ueda; Jean Wilson; Hailong Meng; Tamara P. Blevins; Sui Tsang; Mark Trentalange; Barbara Siconolfi; Koonam Park; Thomas M. Gill; Robert B. Belshe; Susan M. Kaech; Gerald S. Shadel; Steven H. Kleinstein; Albert C. Shaw
• Keywords: Adult; Aged, 80 and over; Male; 0301 basic medicine; Aging; Gene Expression Profiling; Age Factors; Mitochondrial Turnover; DNA, Mitochondrial; Oxidative Phosphorylation; Mitochondria; 3. Good health; 03 medical and health sciences; Gene Expression Regulation; Influenza Vaccines; Influenza, Human; Leukocytes, Mononuclear; Humans; Female; Cells, Cultured; Aged; Genome-Wide Association Study; Oligonucleotide Array Sequence Analysis

To elucidate gene expression pathways underlying age-associated impairment in influenza vaccine response, we screened young (age 21-30) and older (age≥65) adults receiving two consecutive seasons identified those with strong or absent response to vaccine, including a subset of meeting criteria for frailty. PBMCs obtained prior vaccination (Day 0) at day 2 4, 7 28 post-vaccine were subjected microarray analysis. We defined signature also detected induction type I interferon plasma cell responders. The was dysregulated adults, the induced 2, never frail subjects (who all non-responders). mitochondrial responders containing genes mediating biogenesis oxidative phosphorylation that consistent different verified by analyses content protein expression. These results represent first genome-wide transcriptional profiling analysis dynamics following vaccination, implicate changes function as critical factor human responsiveness.