Transcriptional analysis of the molecular basis of human kidney aging using cDNA microarray profiling.
BACKGROUND
The molecular basis of renal aging is not completely understood.


METHODS
We used global gene expression monitoring by cDNA microarrays to identify age associated genes in human kidney samples. Our samples included young (8 weeks-8 years, N= 4), adult (31-46 years, N= 7), and old kidneys (71-88 years, N= 9).


RESULTS
Old kidneys had more glomerulosclerosis, tubular atrophy, interstitial fibrosis, and fibrous intimal thickening in small arteries. We identified approximately 500 genes that were differentially expressed among the three age groups. Old kidneys appeared to have increased extracellular matrix turnover and a nonspecific inflammatory response, combined with a reduction in processes dependent on energy metabolism and mitochondrial function. Quantitative supervised bioinformatics analyses of adult and old kidney expression data correlated the expression of 255 gene profiles with renal pathology scores. Microarray class prediction analysis (PAM) identified 50 unique genes that segregated old kidneys into two distinct clusters: those more similar within age class (OO, N= 5) versus old kidneys more similar to adult kidneys (OA, N= 4). The expression of six functionally significant genes was further validated by quantitative reverse transcription-polymerase chain reaction (RT-PCR) (FN1, MMP7, TNC, SERPIN3A, BPHL, CSPG2) in the experiment group and, subsequently, confirmed independently in 17 additional old and adult age-stratified test kidney samples. The p53 inducible gene, CSPG2, performed best in separating OO kidneys from adults and OA samples in this analysis.


CONCLUSIONS
The method described in this study using independent validation samples can be envisioned to test utility of the identified genes in assessing age-related changes that contribute to decline in renal function.
Melk
Anette
A
Division of Nephrology and Transplantation Immunology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. anette.melk@med.uni-heidelberg.de
Mansfield
Elaine S
ES
Hsieh
Szu-Chuan
SC
Hernandez-Boussard
Tina
T
Grimm
Paul
P
Rayner
David C
DC
Halloran
Philip F
PF
Sarwal
Minnie M
MM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000473:pathology; D051925:CD79 Antigens / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007668:Kidney / Q000473:pathology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D051925:CD79 Antigens