Putative telomere-independent mechanisms of replicative aging reflect inadequate growth conditions.
Telomere shortening is the mechanism underlying replicative aging in fibroblasts. A variety of reports now claim that inactivation of the p16(INK4a)/pRB pathway is required in addition to telomere maintenance for the immortalization of cells such as skin keratinocytes and breast epithelial cells. We here show that the premature growth arrest of these cell types can be explained by an inadequate culture environment. Providing mesenchymal/epithelial interactions by cultivating the telomerase-expressing cells on feeder layers avoids the growth arrest associated with increased p16(INK4a). These results do not support a telomere-independent mechanism of replicative aging.
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9039, USA.
R D
RD
Ramirez
C P
CP
Morales
B S
BS
Herbert
J M
JM
Rohde
C
C
Passons
J W
JW
Shay
W E
WE
Wright
D016475:3T3 Cells; D000818:Animals; D002455:Cell Division; D002461:Cell Line, Transformed; D016922:Cellular Senescence / Q000235:genetics*; D003470:Culture Media; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000201:enzymology; D008321:Mammary Glands, Animal / Q000166:cytology; D051379:Mice; D012867:Skin / Q000166:cytology; D019098:Telomerase / Q000378:metabolism; D016615:Telomere
D003470:Culture Media; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019098:Telomerase