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Utilization of oligonucleotide microarray profiles from C57BL/6J (B6) and DBA/2J (D2) mice to discover aging‐related genes in the lung
Author(s) -
misra vikas,
Lee Hannah,
Singh Anju,
Huang Kewu,
Thimmulappa Rajesh Kumar,
Mitzner Wayne,
Biswal Shyam,
Tankersley Clarke G
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1352-b
Subject(s) - biology , microarray , gene , microarray analysis techniques , gene expression , single nucleotide polymorphism , gene expression profiling , snp , downregulation and upregulation , genetics , microbiology and biotechnology , genotype
The approach of this study is to identify gene expression profiles that provide genomic mechanisms underlying the pathophysiology of the aging lung. Choice of B6 and D2 inbred strains is based on their differences in aging physiology, lung morphometry, and natural longevity. Lungs were harvested from B6 mice at 2, 18, and 26 months and from D2 mice at 2 and 18 months. Purified RNA was put to oligonucleotide microarray analyses using Affymetrix genechips. Biochemical networks were deciphered using Ingenuity Pathways analysis. Genes from these networks were cross‐referenced to single nucleotide polymorphism (SNP) databases for these two strains, and candidate aging‐related SNPs were validated by sequencing entire genes. Approximately 67–89% of expressed genes were upregulated with aging in both strains. Genes in aging D2 mouse lung were uniquely upregulated in xenobiotic detoxification cascades, whereas genes in aging B6 lung were downregulated for heat shock response and upregulated for T cell receptor signaling. IGF and PTEN signaling were differentially expressed between strains at 2 months of age. Several polymorphisms were identified in the regulatory and untranslated regions of the Mmp14 gene. In sum, lungs of B6 and D2 mice age differently at the gene expression level, which when integrated with strain‐dependent SNP associations, leads to a blueprint of regulated aging. NIA AG‐21057 and NHLBI HL‐010342