X-Message-Number: 14138
Date: Fri, 21 Jul 2000 21:42:46 EDT
Subject: resetting the telomeres

1: Biochem Biophys Res Commun 2000 Jul 14;273(3):1095-1098 

Transient Expression of Human Telomerase Extends the Life Span of Normal 
Human Fibroblasts. 

Steinert S, Shay JW, Wright WE 

Department of Cell Biology, University of Texas Southwestern Medical Center, 
5323 Harry Hines Boulevard, Dallas, Texas


We utilized the Cre/lox recombination system to transiently express the 
catalytic subunit of telomerase (hTERT) in normal diploid foreskin 
fibroblasts (BJ cells). A retroviral construct containing an hTERT cDNA, 
flanked by loxP-sites was introduced into near senescent BJ cells (population 
doubling 85). At population doubling (PD) 92, which exceeds the typical life 
span of these cells, we excised the gene via Cre-mediated recombination. All 
clones lost telomerase activity and showed telomere shortening over an 
additional 50 PDs. Interestingly, the average telomere length in these cells 
became shorter than in untreated BJ cells at senescence. This may be due to 
hTERT preferentially elongating the shortest telomeres, leading to greater 
length uniformity. In summary, transient telomerase expression and only a 
very small average telomere elongation by hTERT resulted in a 50% increase in 
life span of human fibroblasts. This suggests a potentially safe use of hTERT 
in tissue engineering. 

Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=14138