Differential effects of in vitro zinc treatment on gene expression in peripheral blood mononuclear cells derived from young and elderly individuals.
Mild zinc deficiency, which is prevalent in vegetarians, diseased individuals, and the general aging population, depresses immunity and increases risk of disease in later life. However, human zinc intervention trials have produced conflicting results, perhaps because many of these trials included young or zinc-sufficient subjects. Since heterogeneity of the adult population may impact on response to dietary zinc, nutrigenomic approaches aimed at understanding the impact of zinc on modulation of gene and protein activities may aid in identifying subsets of the population-in particular the aging population-with increased risk of zinc deficiency who might receive benefit from a dietary zinc intervention and in this way may influence the success of the intervention. In the current study we used nutrigenomic approaches to investigate the impact of age on zinc-regulated gene expression in peripheral blood mononuclear cells. Ingenuity Pathway Analysis (Ingenuity Systems, Redwood City, CA) identified several genetic networks and functional canonical pathways which appeared responsive to zinc that were differentially regulated in young and elderly individuals. These include tryptophan metabolism, eicosanoid signaling, p38 mitogen-activated protein kinase (MAPK) signaling, integrin signaling, purine metabolism, G-protein-coupled receptor signaling, and most significantly, peroxisome proliferator-activated receptor (PPAR) signaling. These data suggest that age impacts strongly on the transcriptional effects of zinc and provides evidence to support the hypothesis that young and elderly individuals may respond differentially to zinc intervention.
Mazzatti
D J
DJ
Unilever Corporate Research, Colworth Park, Sharnbrook, United Kingdom. Dawn.Mazzatti@unilever.com
Malavolta
M
M
White
A J
AJ
Costarelli
L
L
Giacconi
R
R
Muti
E
E
Cipriano
C
C
Powell
J R
JR
Mocchegiani
E
E
D000328:Adult; D000367:Age Factors; D000368:Aged; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000235:genetics / Q000502:physiology; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D047493:PPAR alpha / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D015032:Zinc / Q000494:pharmacology*
D016328:NF-kappa B; D047493:PPAR alpha; D008668:Metallothionein; D015032:Zinc