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

Aging (Albany NY). 2015 Jan;7(1):38-52. doi: 10.18632/aging.100720.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Aging / genetics*
  • Aging / immunology
  • Aging / metabolism
  • Cells, Cultured
  • DNA, Mitochondrial / metabolism*
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation / drug effects*
  • Genome-Wide Association Study
  • Humans
  • Influenza Vaccines / administration & dosage*
  • Influenza, Human / genetics
  • Influenza, Human / immunology
  • Influenza, Human / metabolism
  • Influenza, Human / prevention & control*
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Mitochondria / drug effects*
  • Mitochondria / immunology
  • Mitochondria / metabolism
  • Mitochondrial Turnover / drug effects
  • Mitochondrial Turnover / genetics
  • Oligonucleotide Array Sequence Analysis
  • Oxidative Phosphorylation / drug effects
  • Seasons
  • Time Factors
  • Treatment Outcome
  • Vaccination*
  • Young Adult


  • DNA, Mitochondrial
  • Influenza Vaccines