Microarray analysis of replicative senescence.
BACKGROUND
Limited replicative capacity is a defining characteristic of most normal human cells and culminates in senescence, an arrested state in which cells remain viable but display an altered pattern of gene and protein expression. To survey widely the alterations in gene expression, we have developed a DNA microarray analysis system that contains genes previously reported to be involved in aging, as well as those involved in many of the major biochemical signaling pathways.


RESULTS
Senescence-associated gene expression was assessed in three cell types: dermal fibroblasts, retinal pigment epithelial cells, and vascular endothelial cells. Fibroblasts demonstrated a strong inflammatory-type response, but shared limited overlap in senescent gene expression patterns with the other two cell types. The characteristics of the senescence response were highly cell-type specific. A comparison of early- and late-passage cells stimulated with serum showed specific deficits in the early and mid G1 response of senescent cells. Several genes that are constitutively overexpressed in senescent fibroblasts are regulated during the cell cycle in early-passage cells, suggesting that senescent cells are locked in an activated state that mimics the early remodeling phase of wound repair.


CONCLUSIONS
Replicative senescence triggers mRNA expression patterns that vary widely and cell lineage strongly influences these patterns. In fibroblasts, the senescent state mimics inflammatory wound repair processes and, as such, senescent cells may contribute to chronic wound pathologies.
Shelton
D N
DN
Molecular Biology and Biochemistry Group, Geron Corporation, 230 Constitution Drive, Menlo Park, California, 94025, USA.
Chang
E
E
Whittier
P S
PS
Choi
D
D
Funk
W D
WD
D001790:Blood Physiological Phenomena; D002455:Cell Division; D019070:Cell Lineage; D002478:Cells, Cultured / Q000187:drug effects; D016922:Cellular Senescence / Q000235:genetics*; D003470:Culture Media / Q000494:pharmacology; D004261:DNA Replication; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D020224:Expressed Sequence Tags; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007249:Inflammation; D020411:Oligonucleotide Array Sequence Analysis; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D012867:Skin / Q000166:cytology; D016615:Telomere / Q000648:ultrastructure; D014945:Wound Healing / Q000235:genetics
D003470:Culture Media; D012333:RNA, Messenger