Exploration of replicative senescence-associated genes in human dermal fibroblasts by cDNA microarray technology.
The aging process is known to be regulated by specific genes in various organisms, including yeast, the nematode C. elegans, fruitflies and mice. To explore the novel genes involved in aging process, we applied cDNA microarray technology to a replicative senescence model of human dermal fibroblasts (HDF). Eighty-four genes, including inflammatory genes, cell cycle regulatory genes, cytoskeletal genes, and metabolic genes were found to show more than two fold expressional differences in young and old fibroblasts. Furthermore, 31 genes were confirmed to be up- or down-regulated during replicative senescence by semi-quantitative RT-PCR. The overexpressions of several genes including CD36, putative lymphocyte G0/G1 switch gene (G0S2), tumor protein D52-like 1 (TPD52L1), chemokine (C-X-C motif) ligand 6, myxovirus resistant gene 1 (MX1), and the down-regulation of the immunoglobulin superfamily containing leucine-rich repeat (ISLR), neurotrimin, insulin-like growth factor 2 associated protein (IGF2A), and apoptosis-related RNA binding protein (NAPOR3) were newly identified. These results suggest that fibroblasts show the deregulation of various cellular processes, such as inflammatory response, mitosis, cell adhesion, transport, signal transduction, and metabolism during replicative senescence.
Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, 317-1 Daemyung-Dong, Daegu 705-717, South Korea.
In Kyung
IK
Yoon
Hyun Kyoung
HK
Kim
Yu Kyoung
YK
Kim
In-Hwan
IH
Song
Wankee
W
Kim
Seongyong
S
Kim
Suk-Hwan
SH
Baek
Jung Hye
JH
Kim
Jae-Ryong
JR
Kim
D002455:Cell Division / Q000235:genetics; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics* / Q000502:physiology; D002648:Child; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012867:Skin / Q000166:cytology*; D015854:Up-Regulation