Abstract
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.
Highlights
Telomeres are regions at the ends of chromosomes characterized by a repeating TTAGGG sequence
The cells were treated with TA-65, HTA, or DMSO and samples were taken to measure telomerase activity 72 h after primary stimulation and the process repeated after 18–21 days for a secondary stimulation
Our results show that during a primary stimulation, TA-65 at both 10−5 and 10−6 gm/mL dilution increased telomerase activity on average 1.57 to 1.42 fold, respectively, when compared to the DMSO control, (Figure 1A)
Summary
Telomeres are regions at the ends of chromosomes characterized by a repeating TTAGGG sequence. During DNA replication, DNA is synthesized by a continuous leading strand and by a discontinuous lagging strand, which are primed by an RNA polymerase. Because of steric hindrance between the DNA polymerase and the required RNA priming at the ends of chromosomes, the lagging strand cannot be completely synthesized. With each cell division, the DNA length shortens at the ends within the telomere region. The chromosome ends become reactive, leading to chromosomal fusions, resulting in DNA molecules with two centromeres, referred to as a dicentric chromosome [3]. Dicentric chromosomes can be pulled apart in opposite directions, leading to breaks in the chromosomes, repeating the cycle in a process known as breakage-fusion-bridge cycles [4]. The telomere region, acts to prevent these fusions by capping the ends of the chromosomes and maintaining DNA integrity
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