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Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination
- Source :
- Aging (Albany NY)
- Publication Year :
- 2015
- Publisher :
- Impact Journals, LLC, 2015.
-
Abstract
- 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 influenza vaccine in two consecutive seasons and identified those with strong or absent response to vaccine, including a subset of older adults meeting criteria for frailty. PBMCs obtained prior to vaccination (Day 0) and at day 2 or 4, day 7 and day 28 post-vaccine were subjected to gene expression microarray analysis. We defined a response signature and also detected induction of a type I interferon response at day 2 and a plasma cell signature at day 7 post-vaccine in young responders. The response signature was dysregulated in older adults, with the plasma cell signature induced at day 2, and was never induced in frail subjects (who were all non-responders). We also identified a mitochondrial signature in young vaccine responders containing genes mediating mitochondrial biogenesis and oxidative phosphorylation that was consistent in two different vaccine seasons and verified by analyses of mitochondrial content and protein expression. These results represent the first genome-wide transcriptional profiling analysis of age-associated dynamics following influenza vaccination, and implicate changes in mitochondrial biogenesis and function as a critical factor in human vaccine responsiveness.
- Subjects :
- Adult
Male
Aging
Time Factors
Microarray
Influenza vaccine
Mitochondrial Turnover
frailty
Biology
Mitochondrion
DNA, Mitochondrial
Oxidative Phosphorylation
Young Adult
03 medical and health sciences
0302 clinical medicine
Influenza, Human
Humans
Cells, Cultured
Aged
Oligonucleotide Array Sequence Analysis
030304 developmental biology
Aged, 80 and over
Regulation of gene expression
0303 health sciences
Gene Expression Profiling
Vaccination
Age Factors
Cell Biology
Virology
Mitochondria
3. Good health
Gene expression profiling
Treatment Outcome
Gene Expression Regulation
Mitochondrial biogenesis
Influenza Vaccines
Immunology
Leukocytes, Mononuclear
gene expression
Female
Seasons
influenza vaccine
microarray
030217 neurology & neurosurgery
Genome-Wide Association Study
Research Paper
Subjects
Details
- ISSN :
- 19454589
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Aging
- Accession number :
- edsair.doi.dedup.....e0a93a8dfd7a2367536378f22021eb1d