Functional Assessment of Pharmacological Telomerase Activators in Human T Cells

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.

The Use of Natural Agents to Counteract Telomere Shortening: Effects of a Multi-Component Extract of Astragalus mongholicus Bunge and Danazol

“…Counteracting telomere attrition and its consequences has been a main target for research during the last decade [7,22]. Regenerative medicine has also focused on strategies to maintain telomere length [31]. Androgens, such as danazol, have been used to promote telomere elongation in patients with telomeropathies or telomere syndromes [21].…”

“…In addition to their antioxidant, anti-inflammatory, immunoregulatory and anticancer effects, extracts of Astragalus spp. have been shown to exert beneficial effects on telomeres and to stimulate telomerase activity in various models [22,23,31]. Most studies investigated cycloastragenol (TA-65), a single chemical entity isolated by a proprietary purification process from a root extract of Astragalus membranaceus [22,24,25,31,32].…”

Antiaging effects of bioactive molecules isolated from plants and fungi

“…The potential to reactivate telomerase in somatic cells has shown promise to prevent senescence and increase lifespan. A natural plant compound called cycloastragenol [ 28 ] isolated from the roots of Astragalus membranaceus (a plant used as a tonic in TCM) has been reported to activate telomerase in cultured human CD4 + and CD8 + T lymphocytes . Cycloastragenol delayed telomere shortening, increased replicative capacity, and improved immune function in cultured CD8 + T lymphocytes isolated from human immunodeficiency virus‐positive individuals .…”

“…A natural plant compound called cycloastragenol [28] isolated from the roots of Astragalus membranaceus (a plant used as a tonic in TCM) has been reported to activate telomerase in cultured human CD4 + and CD8 + T lymphocytes. [210][211][212] Cycloastragenol delayed telomere shortening, increased replicative capacity, and improved immune function in cultured CD8 + T lymphocytes isolated from human immunodeficiency virus-positive individuals. 213 In female mice, cycloastragenol, also called TA-65, increased telomere length in some tissues, most notably in the liver, and improved some healthspan indicators including glucose tolerance, osteoporosis, and skin aging but no lifespan increase was observed.…”

35 The Future of Rejuvenation Techniques for Aging Facial Skin

“…49 Research continues in using cycloastragenol from the Astragalus plant that has been shown in one study to activate telomerase. 50 Telomerase activators have suggested a slowing of aging in mice. 51,52 Other studies on affecting telomeres and increasing protective telomerase continue including lifestyle and dietary factors.…”