Subject(s)
Aging/physiology , Cellular Senescence/physiology , Molecular Chaperones/physiology , Prostatic Neoplasms/physiopathology , Aging/genetics , Animals , Benzoquinones , Cellular Senescence/genetics , HSP90 Heat-Shock Proteins/antagonists & inhibitors , Humans , Lactams, Macrocyclic , Lactones/pharmacology , Macrolides , Male , Mice , Molecular Chaperones/drug effects , Quinones/pharmacology , Telomerase/biosynthesis , Telomere/genetics , Telomere/physiologyABSTRACT
Retroviral infection of hTERT, the catalytic component of telomerase, into BJ fibroblasts (population doubling 28) resulted in reconstitution of telomerase activity, telomere maintenance, and extension of in vitro lifespan. The hTERT-infected cells also exhibited increased growth rate and colony forming efficiency relative to controls, while remaining contact-inhibited and maintaining a p53-mediated damage response following gamma-irradiation. All single cell-derived BJ-hTERT clones grew faster than the hTERT mass cultures and maintained telomeres; however, neither telomerase activity levels nor mean telomere length correlated with the growth rate. Introduction of hTERT rescued aged BJ fibroblasts from senescence via a telomere-dependent mechanism and provided renewed proliferative potential. Collectively, our data indicate that both early and late in the cellular lifespan of human cells, ectopic expression of telomerase using a retroviral system provides a growth advantage while maintaining normal cellular characteristics.
