Circulating blood leukocyte gene expression profiles: effects of the Ames dwarf mutation on pathways related to immunity and inflammation.
Aging is associated with a decline of immune competence and an increase in markers of inflammation. There is considerable evidence that inflammatory processes play a role in aging and the determination of lifespan. Hypopituitary Ames dwarf mice have extended longevity and exhibit many symptoms of delayed aging, although various aspects of immune function are suppressed in the mutants. In the present study, the expression of genes related to immunity and inflammation was compared in peripheral blood leukocytes (PBL) from Ames dwarf and normal mice using Affymetrix GeneChip arrays. Among the more than 3000 probe sets that were differentially expressed, 273 were identified as being associated with immunity and/or inflammation. Pathway analysis revealed interactions among 91 of these probe sets, centered on casp3, bcl2, il4, prkca, mapk14 and TGFbeta1. Ames dwarf mice had reduced leukocyte expression of casp3 and TGFbeta and increased expression of Bcl2. Alterations in the expression of these genes suggest likely functional changes in apoptosis, B and T cell homeostasis, prostaglandin synthesis, humoral immunity, chemokine activity, complement activation, hemostasis and wound healing pathways. Collectively, these results suggest that activation of both anti-inflammatory pathways and an anti-clotting mechanism combined with reduced turnover of leukocytes may contribute to delayed aging and extended longevity of Ames dwarf mice. We are also aware that alterations in gene expression in PBLs can be due to different composition of PBL populations when comparing Ames dwarf to WT animals, and it will be interesting to investigate these genes in particular PBL populations in the future. However, whole leukocytes population represents the function of immune system in these organisms.
Dhahbi
Joseph
J
BioMarker Pharmaceuticals Inc., 5941 Optical Court, San Jose, CA 95138, USA. jdhahbi@chori.org
Li
Xichen
X
Tran
Tim
T
Masternak
Michal M
MM
Bartke
Andrzej
A
D000375:Aging / Q000235:genetics* / Q000276:immunology*; D000818:Animals; D004393:Dwarfism, Pituitary / Q000235:genetics* / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D007962:Leukocytes / Q000276:immunology* / Q000378:metabolism*; D008136:Longevity / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction