Cycloastragenol

Cycloastragenol is a triterpenoid saponin isolated from various species in the genus Astragalus that is purported to have telomerase activation activity. A preliminary in vitro study on human CD4 and CD8 T cells found that cycloastragenol may moderately increase telomerase activity and inhibit the onset of cellular senescence.[1]

Cycloastragenol
Names
Other names
Cyclogalegigenin; Astramembrangenin
Identifiers
3D model (JSmol)
ChemSpider
Properties
C30H50O5
Molar mass 490.72 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

History

Cycloastragenol was patented by Geron Corporation and sold to Telomerase Activation Sciences in early 2013 who are developing it as a product named TA-65.[2][3] Bill Andrews of Sierra Sciences has done testing on the anti-aging aspect of TA-65;[4], as well as Maria Blasco in the journal Aging Cell, finding no increase in murine median or mean lifespan but some physiological anti-aging effects without augmenting cancer incidence.[5] TA sciences was served with a consent order by the Federal Trade Commission for deceptive advertising implying that TA-65 can reverse aging and repair DNA damage.[6]

Potential pharmacology

Its mode of action is purported to be the activation of the human enzyme telomerase.[1]

Cycloastragenol intake improved health span but not lifespan in normal mice.[5]

As part of a study sponsored by RevGenetics, the cycloastragenol-based product TA-65 was tested by UCLA scientist Rita B. Effros and RevGenetics[7] scientist Hector F. Valenzuela. The small study (using T-cells taken from 6 participants) found that TA-65 activated telomerase in cultured cells in all samples, while another Astragalus extract did not.[8] The clinical significance of this work is uncertain.

Toxicity testing is limited and safety for the human consumer has not been adequately demonstrated. TA-65 was shown to improve biological markers associated with human health span through the lengthening of short telomeres and rescuing of old cells, although the significance of these findings in actual life expectancy is unknown.[9] Publications in high-impact peer-reviewed journals are lacking however, and much of the online documentation supporting its use is sponsored by its manufacturers.

As disordered telomerase function is a feature of almost all cancers,[10] there is an unproven, but theoretical risk of oncogene-mediated cancer promotion through the use of telomerase activators.

References
  1. Valenzuela, Hector F; Fuller, Thomas; Edwards, Jim; Finger, Danielle; Molgora, Brenda (April 2009). "Cycloastragenol extends T cell proliferation by increasing telomerase activity". J Immunol. 182 (1_MeetingAbstracts): 90.30. Retrieved 19 July 2015.
  2. Borrell, Brendan (2012-08-02). "Lawsuit challenges anti-ageing claims". Nature News. 488 (7409): 18. doi:10.1038/488018a. Retrieved 2021-01-28.
  3. "Application to market Cycloastragenol". acnfp.food.gov.uk. UK Advisory Committee on Novel Foods and Processes. Retrieved 29 Nov 2017.
  4. Dr. Bill Andrews anti-aging test of TA-65
  5. Bernardes; de Jesus, B; Schneeberger, K; Vera, E; Tejera, A; Harley, CB; Blasco, MA (2011). "The telomerase activator TA-65 elongates short telomeres and increases health span of adult/old mice without increasing cancer incidence". Aging Cell. 10 (4): 604–21. doi:10.1111/j.1474-9726.2011.00700.x. PMC 3627294. PMID 21426483.
  6. "FTC Approves Final Consent Order in Telomerase Activation Sciences Deceptive Advertising Case". ftc.gov. Federal Trade Commission. Retrieved 28 January 2021.
  7. TA-65
  8. Valenzuela, Hector F; Effros, Rita B; Dimler, Taylor; Sweeney, Greg; Bateman, RileyH; Malgora, Brenda (14 January 2013). "Functional Assessment of Pharmacological Telomerase Activators in Human T Cells". Cells. 2 (1): 57–66. doi:10.3390/cells2010057. PMC 3972662. PMID 24709644.
  9. Harley, Calvin B; Liu, Weimin; Blasco, Maria; Vera, Elsa; Andrews, William H; Briggs, Laura A; Raffaele, Joseph M (1 February 2011). "A Natural Product Telomerase Activator As Part of a Health Maintenance Program". Rejuvenation Research. 14 (1): 45–56. doi:10.1089/rej.2010.1085. PMC 3045570. PMID 20822369.
  10. Shay, JW; Wright, WE (1 January 2001). "Telomeres and telomerase: implications for cancer and aging". Radiation Research. 155 (1 pt 2): 188–193. Bibcode:2001RadR..155..188S. doi:10.1667/0033-7587(2001)155[0188:tatifc]2.0.co;2. PMID 11121233.
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