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Names | |
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IUPAC name 24α,20-Epoxy-9,19-cyclo-9β-lanost-24-ene-3β,6α,16β,25-tetrol | |
Systematic IUPAC name (1R,2S,3aS,3bS,5S,5aR,7S,9aR,10aS,12aR)-1-[(2R,5S)-5-(2-Hydroxypropan-2-yl)-2-methyloxolan-2-yl]-3a,6,6,12a-tetramethyltetradecahydro-1H,10H-cyclopenta[a]cyclopropa[e]phenanthrene-2,5,7-triol | |
Other names Cyclogalegigenin; Astramembrangenin | |
Identifiers | |
3D model (JSmol) | |
ChemSpider | |
PubChem CID | |
UNII | |
CompTox Dashboard (EPA) | |
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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). |
Cycloastragenol is a triterpenoid isolated from various legume 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 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] [ unreliable source? ], 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]
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.
A telomere is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes. Telomeres are a widespread genetic feature most commonly found in eukaryotes. In most, if not all species possessing them, they protect the terminal regions of chromosomal DNA from progressive degradation and ensure the integrity of linear chromosomes by preventing DNA repair systems from mistaking the very ends of the DNA strand for a double-strand break.
Telomerase, also called terminal transferase, is a ribonucleoprotein that adds a species-dependent telomere repeat sequence to the 3' end of telomeres. A telomere is a region of repetitive sequences at each end of the chromosomes of most eukaryotes. Telomeres protect the end of the chromosome from DNA damage or from fusion with neighbouring chromosomes. The fruit fly Drosophila melanogaster lacks telomerase, but instead uses retrotransposons to maintain telomeres.
Elizabeth Helen Blackburn, is an Australian-American Nobel laureate who is the former president of the Salk Institute for Biological Studies. In 1984, Blackburn co-discovered telomerase, the enzyme that replenishes the telomere, with Carol W. Greider. For this work, she was awarded the 2009 Nobel Prize in Physiology or Medicine, sharing it with Greider and Jack W. Szostak, becoming the first Australian woman Nobel laureate.
Geron Corporation is a biotechnology company located in Foster City, California, which specializes in developing and commercializing therapeutic products for cancer that inhibit telomerase.
Dyskeratosis congenita (DKC), also known as Zinsser-Engman-Cole syndrome, is a rare progressive congenital disorder with a highly variable phenotype. The entity was classically defined by the triad of abnormal skin pigmentation, nail dystrophy, and leukoplakia of the oral mucosa, and MDS/AML, but these components do not always occur. DKC is characterized by short telomeres. Some of the manifestations resemble premature ageing and cognitive impairment can be a feature. The disease initially mainly affects the skin, but a major consequence is progressive bone marrow failure which occurs in over 80%, causing early mortality.
Eternal youth is the concept of human physical immortality free of ageing. The youth referred to is usually meant to be in contrast to the depredations of aging, rather than a specific age of the human lifespan. Eternal youth is common in mythology, and is a popular theme in fiction.
Carolyn Widney Greider is an American molecular biologist and Nobel laureate. She joined the University of California, Santa Cruz as a Distinguished Professor in the department of molecular, cell, and developmental biology in October 2020.
Telomerase reverse transcriptase is a catalytic subunit of the enzyme telomerase, which, together with the telomerase RNA component (TERC), comprises the most important unit of the telomerase complex.
Telomerase RNA component, also known as TR, TER or TERC, is an ncRNA found in eukaryotes that is a component of telomerase, the enzyme used to extend telomeres. TERC serves as a template for telomere replication by telomerase. Telomerase RNAs differ greatly in sequence and structure between vertebrates, ciliates and yeasts, but they share a 5' pseudoknot structure close to the template sequence. The vertebrate telomerase RNAs have a 3' H/ACA snoRNA-like domain.
Sierra Sciences, LLC is a biotechnology company founded by William H. Andrews, former director of molecular biology at Geron Corporation. Andrews founded Sierra Sciences in 1999 in Reno, Nevada with the goal of preventing and/or reversing cellular senescence, and ultimately curing diseases associated with human aging, including the aging process itself.
Telomere-binding proteins function to bind telomeric DNA in various species. In particular, telomere-binding protein refers to TTAGGG repeat binding factor-1 (TERF1) and TTAGGG repeat binding factor-2 (TERF2). Telomere sequences in humans are composed of TTAGGG sequences which provide protection and replication of chromosome ends to prevent degradation. Telomere-binding proteins can generate a T-loop to protect chromosome ends. TRFs are double-stranded proteins which are known to induce bending, looping, and pairing of DNA which aids in the formation of T-loops. They directly bind to TTAGGG repeat sequence in the DNA. There are also subtelomeric regions present for regulation. However, in humans, there are six subunits forming a complex known as shelterin.
William Henry Andrews is an American molecular biologist and gerontologist whose career has centered on searching for a cure for human aging. Andrews is the founder and president of the biotechnology company Sierra Sciences. In the 1990s, he led the team at Geron Corporation that was the first to successfully identify the genes for human enzyme telomerase. This enzyme is responsible for preventing telomeres from shortening in human primordial germ cells.
Shelterin is a protein complex known to protect telomeres in many eukaryotes from DNA repair mechanisms, as well as to regulate telomerase activity. In mammals and other vertebrates, telomeric DNA consists of repeating double-stranded 5'-TTAGGG-3' (G-strand) sequences along with the 3'-AATCCC-5' (C-strand) complement, ending with a 50-400 nucleotide 3' (G-strand) overhang. Much of the final double-stranded portion of the telomere forms a T-loop (Telomere-loop) that is invaded by the 3' (G-strand) overhang to form a small D-loop (Displacement-loop).
Telomeric repeat–containing RNA (TERRA) is a long non-coding RNA transcribed from telomeres - repetitive nucleotide regions found on the ends of chromosomes that function to protect DNA from deterioration or fusion with neighboring chromosomes. TERRA has been shown to be ubiquitously expressed in almost all cell types containing linear chromosomes - including humans, mice, and yeasts. While the exact function of TERRA is still an active area of research, it is generally believed to play a role in regulating telomerase activity as well as maintaining the heterochromatic state at the ends of chromosomes. TERRA interaction with other associated telomeric proteins has also been shown to help regulate telomere integrity in a length-dependent manner.
María Antonia Blasco Marhuenda, known as María Blasco, is a Spanish molecular biologist. She is the current director of the Spanish National Cancer Research Centre.
Bryant Villeponteau is an American scientist, entrepreneur, and longevity expert who has worked in both academia and industry.
BioViva is an American biotechnology company, based in Bainbridge Island, Washington, researching treatments to interfere in the ageing process in humans.
Life Length is a biotechnology company. Located in Madrid, it provides telomere diagnostics as well as telomerase measurement.
Epitalon is a synthetic peptide, telomerase activator, and putative anti-aging compound, which was identified as the putative active component of a bovine pineal gland extract known as epithalamin.
Telomeres, the caps on the ends of eukaryotic chromosomes, play critical roles in cellular aging and cancer. An important facet to how telomeres function in these roles is their involvement in cell cycle regulation.