Functional assessment of pharmacological telomerase activators in human T cells.
Telomeres are structures at the ends of chromosomes that shorten during cell division and eventually signal an irreversible state of growth arrest known as cellular senescence. To delay this cellular aging, human T cells, which are critical in the immune control over infections and cancer, activate the enzyme telomerase, which binds and extends the telomeres. Several different extracts from the Astragalus membranaceus root have been documented to activate telomerase activity in human T cells. The objective of this research was to compare two extracts from Astragalus membranaceus, TA-65 and HTA, for their effects on both telomerase and proliferative activity of human CD4 and CD8 T cells. Our results demonstrate that, TA-65 increased telomerase activity significantly (1.3 to 3.3-fold relative to controls) in T cell cultures from six donors tested, whereas HTA only increased telomerase levels in two out of six donors. We also demonstrate that TA-65 activates telomerase by a MAPK- specific pathway. Finally, we determine that during a three-day culture period, only the T cells treated with the TA-65 extract showed a statistically significant increase in proliferative activity. Our results underscore the importance of comparing multiple telomerase activators within the same experiment, and of including functional assays in addition to measuring telomerase activity.
Department of Biology, Whittier College,13406 Philadelphia Street, P.O. Box 634, Whittier 90608, CA, USA. bmolgora@poets.whittier.edu.
Brenda
B
Molgora
Department of Biology, Whittier College,13406 Philadelphia Street, P.O. Box 634, Whittier 90608, CA, USA. rbateman@poets.whittier.edu.
Riley
R
Bateman
Department of Biology, Whittier College,13406 Philadelphia Street, P.O. Box 634, Whittier 90608, CA, USA. gsweeney@poets.whittier.edu.
Greg
G
Sweeney
Department of Biology, Whittier College,13406 Philadelphia Street, P.O. Box 634, Whittier 90608, CA, USA. dfinger@poets.whittier.edu.
Danielle
D
Finger
Department of Biology, Whittier College,13406 Philadelphia Street, P.O. Box 634, Whittier 90608, CA, USA. mdimler@poets.whittier.edu.
Taylor
T
Dimler
Department of Pathology and Lab Medicine, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles 90095-1732, CA, USA. Reffros@mednet.ucla.edu.
Rita B
RB
Effros
Department of Biology, Whittier College,13406 Philadelphia Street, P.O. Box 634, Whittier 90608, CA, USA. hvalenzu@whittier.edu.
Hector F
HF
Valenzuela