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.

Various natural products have been proposed to both increase health at the organismic level, and delay the onset of cellular aging. Of particular interest is resveratrol, a phytoalexin that has been demonstrated to have cardioprotective effects and to slow the progression of a variety of illnesses, including various types of cancers. More recently, resveratrol has been demonstrated to increase the maximum lifespan of model organisms, such as C. elegans, D. melanogaster and N. furzeri. However, the potential health benefits of resveratrol and other similar compounds on the human immune response have not been adequately addressed. We have, therefore, initiated research to determine the in vitro effects of the nutraceuticals resveratrol, and its analogs (polydatin and acetyl-resveratrol), as well as curcumin on a variety of human T cell functions. In this study we evaluated the effect of these compounds on proliferative potential, telomerase activity, expression of costimulatory and memory surface markers and sirtuin gene expression profiles of both human CD4 and CD8 T cells. Our data show that these compounds stimulated strong dose-dependent anti-inflammatory responses, and upregulated surface protein markers associated with the suppression of T cell activity. Our preliminary results suggest that these compounds may function to down-modulate ongoing CD4 and CD8 immune activity, while, nevertheless, poising the T cells for a subsequent immune response.