ASTCOQ02, a natural telomerase activator, lengthens telomeres in humans in a middle-aged population A randomized, double-blind, placebo-controlled study (original) (raw)
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Rejuvenation research, 2016
TA-65 is a dietary supplement based on an improved formulation of a small molecule telomerase activator that was discovered in a systematic screening of natural product extracts from traditional Chinese medicines. This study summarizes the findings on telomere length (TL) changes from a randomized, double blind, placebo controlled study of TA-65 over a 1 year period. The study was conducted on 117 relatively healthy cytomegalovirus-positive subjects aged 53-87 years old. Subjects taking the low dose of TA-65 (250 U) significantly increased TL over the 12 months period (530 ± 180 bp; p = 0.005), whereas subjects in the placebo group significantly lost TL (290 ± 100 bp; p = 0.01). The high dose of TA-65 (1000 U) showed a trend of improvements in TL compared with that of the placebo group; however, the improvements did not reach statistical significance. TL changes in the low-dose group were similar for both median and 20th percentile TLs. The findings suggest that TA-65 can lengthen t...
Biomedicines
A link between telomere shortening and oxidative stress was found in aging people and patients with cancer or inflammatory diseases. Extracts of Astragalus spp. are known to stimulate telomerase activity, thereby compensating telomere shortening. We characterized a multi-component hydroethanolic root extract (HRE) of Astragalus mongholicus Bunge and assessed its effects on telomeres compared to those of danazol. Astragalosides I to IV, flavonoids, amino acids and sugars were detected in the HRE. Samples of peripheral blood lymphocytes with short telomeres from 18 healthy donors (mean age 63.5 years; range 32–86 years) were exposed to a single dose of 1 µg/mL HRE or danazol for three days. Telomere length and telomerase expression were then measured. Significant elongation of telomeres associated to a less toxicity was observed in lymphocytes from 13/18 donors following HRE treatment (0.54 kb (0.15–2.06 kb)) and in those from 9/18 donors after danazol treatment (0.95 kb (0.06–2.06 kb...
First Randomized, Double-Blind, Placebo-Controlled Study to Show Telomere Lengthening in Humans
2019
TA-65 is a dietary supplement based on an improved formulation of a small molecule telomerase activator that was discovered in a systematic screening of natural product extracts from traditional Chinese medicines. This study summarizes the findings on telomere length (TL) changes from a randomized, double blind, placebo controlled study of TA-65 over a 1 year period. The study was conducted on 117 relatively healthy cytomegalovirus-positive subjects aged 53–87 years old. Subjects taking the low dose of TA-65 (250U) significantly increased TL over the 12 months period (530– 180 bp; p = 0.005), whereas subjects in the placebo group significantly lost TL (290– 100 bp; p = 0.01). The high dose of TA-65 (1000U) showed a trend of improvements in TL compared with that of the placebo group; however, the improvements did not reach statistical significance. TL changes in the low-dose group were similar for both median and 20th percentile TLs. The findings suggest that TA-65 can lengthen telom...
Rejuvenation Research, 2013
Most human cells lack sufficient telomerase to maintain telomeres, hence these genetic elements shorten with time and stress, contributing to aging and disease. In January, 2007, a commercial health maintenance program, PattonProtocol-1, was launched that included a natural product-derived telomerase activator (TA-65 Ò , 10-50 mg daily), a comprehensive dietary supplement pack, and physician counseling/laboratory tests at baseline and every 3-6 months thereafter. We report here analysis of the first year of data focusing on the immune system. Low nanomolar levels of TA-65 Ò moderately activated telomerase in human keratinocytes, fibroblasts, and immune cells in culture; similar plasma levels of TA-65 Ò were achieved in pilot human pharmacokinetic studies with single 10-to 50-mg doses. The most striking in vivo effects were declines in the percent senescent cytotoxic (CD8 þ /CD28 À ) T cells (1.5, 4.4, 8.6, and 7.5% at 3, 6, 9, and 12 months, respectively; p ¼ not significant [N.S.], 0.018, 0.0024, 0.0062) and natural killer cells at 6 and 12 months ( p ¼ 0.028 and 0.00013, respectively). Most of these decreases were seen in cytomegalovirus (CMV) seropositive subjects. In a subset of subjects, the distribution of telomere lengths in leukocytes at baseline and 12 months was measured. Although mean telomere length did not increase, there was a significant reduction in the percent short (<4 kbp) telomeres ( p ¼ 0.037). No adverse events were attributed to PattonProtocol-1. We conclude that the protocol lengthens critically short telomeres and remodels the relative proportions of circulating leukocytes of CMV þ subjects toward the more ''youthful'' profile of CMV À subjects. Controlled randomized trials are planned to assess TA-65 Ò -specific effects in humans.
Cellular and Molecular Biology, 2019
Telomere shortening is involved in age-related disorders, such as cancer and cardiovascular diseases. Recently, telomerase re-activation strategies have been proposed to counteract telomere shortening and its consequences. Here, we investigated the benefit of dietary supplementation with a mix of S-adenosyl-methionine (SAMe) and a polysaccharide extract of Astragalus (APS) on telomere length of circulating lymphocytes of healthy volunteers. Blood lymphocytes of a cohort of 26 healthy volunteers who were administrated the mix of SAMe and APS in a food supplement for one year were collected. In vitro treatment of blood lymphocytes of healthy volunteers with the mix was also performed. A cohort of 150 healthy volunteers was used as a control. Telomere length was measured by Q-FISH. The micronucleus assay was performed to detect genotoxicity of the mix. The telomeres of circulating lymphocytes of the cohort of 26 donors supplemented with the mix were significantly longer than those of m...
Discovery of potent telomerase activators: Unfolding new therapeutic and anti-aging perspectives
Molecular Medicine Reports
Telomere length, a marker of cellular aging, decreases with age and it has been associated with aging-related diseases. environmental factors, including diet and lifestyle factors, affect the rate of telomere shortening which can be reversed by telomerase. Telomerase activation by natural molecules has been suggested to be an anti-aging modulator that can play a role in the treatment of aging-related diseases. This study aimed to investigate the effect of natural compounds on telomerase activity in human peripheral blood mononuclear cells (PBMcs). The tested compounds included Centella asiatica extract formulation (08aGTlF), astragalus extract formulation (nutrient 4), Ta-65 (containing Astragalus membranaceus extract), oleanolic acid (oa), maslinic acid (Ma), and 3 multi-nutrient formulas (nutrients 1, 2 and 3) at various concentrations. The mean absorbance values of telomerase activity measured following treatment with some of the above-mentioned formulations were statistically significantly higher compared to those of the untreated cells. in particular, in order of importance with respect to telomerase activation from highest to lowest, 08aGTlF, oa, nutrient 4, Ta-65, Ma, nutrient 3 and nutrient 2, triggered statistically significant increase in telomerase activity compared to the untreated cells. 08aGTlF reached the highest levels of telomerase activity reported to date, at least to our knowledge, increasing telomerase activity by 8.8 folds compared to untreated cells, while nutrient 4 and oa were also potent activators (4.3-fold and 5.9-fold increase, respectively). on the whole, this study indicates that the synergistic effect of nutrients and natural compounds can activate telomerase and produce more potent formulations. Human clinical studies using these formulations are required to evaluate their mode of action. This would reveal the health benefits of telomerase activation through natural molecules and would shed new light onto the treatment of aging-related diseases.
Article Functional Assessment of Pharmacological Telomerase
2013
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.
Molecular Medicine Reports, 2023
Telomeres are major contributors to cell fate and aging through their involvement in cell cycle arrest and senescence. The accelerated attrition of telomeres is associated with aging-related diseases, and agents able to maintain telomere length (Tl) through telomerase activation may serve as potential treatment strategies. The aim of the present study was to assess the potency of a novel telomerase activator on Tl and telomerase activity in vivo. The administration of a nutraceutical formulation containing Centella asiatica extract, vitamin c, zinc and vitamin d3 in 18-month-old rats for a period of 3 months reduced the telomere shortening rate at the lower supplement dose and increased mean the Tl at the higher dose, compared to pre-treatment levels. Tl was determined using the Q-FiSH method in peripheral blood mononuclear cells collected from the tail vein of the rats and cultured with RPMI-1640 medium. In both cases, TLs were significantly longer compared to the untreated controls (P≤0.001). In addition, telomerase activity was increased in the peripheral blood mononuclear cells of both treatment groups. on the whole, the present study demonstrates that the nutraceutical formulation can maintain or even increase Tl and telomerase activity in middle-aged rats, indicating a potential role of this formula in the prevention and treatment of aging-related diseases.
A Natural Product Telomerase Activator As Part of a Health Maintenance Program
Rejuvenation Research, 2011
Most human cells lack sufficient telomerase to maintain telomeres, hence these genetic elements shorten with time and stress, contributing to aging and disease. In January, 2007, a commercial health maintenance program, PattonProtocol-1, was launched that included a natural product-derived telomerase activator (TA-65 Ò , 10-50 mg daily), a comprehensive dietary supplement pack, and physician counseling/laboratory tests at baseline and every 3-6 months thereafter. We report here analysis of the first year of data focusing on the immune system. Low nanomolar levels of TA-65 Ò moderately activated telomerase in human keratinocytes, fibroblasts, and immune cells in culture; similar plasma levels of TA-65 Ò were achieved in pilot human pharmacokinetic studies with single 10-to 50-mg doses. The most striking in vivo effects were declines in the percent senescent cytotoxic (CD8 þ /CD28 À ) T cells (1.5, 4.4, 8.6, and 7.5% at 3, 6, 9, and 12 months, respectively; p ¼ not significant [N.S.], 0.018, 0.0024, 0.0062) and natural killer cells at 6 and 12 months ( p ¼ 0.028 and 0.00013, respectively). Most of these decreases were seen in cytomegalovirus (CMV) seropositive subjects. In a subset of subjects, the distribution of telomere lengths in leukocytes at baseline and 12 months was measured. Although mean telomere length did not increase, there was a significant reduction in the percent short (<4 kbp) telomeres ( p ¼ 0.037). No adverse events were attributed to PattonProtocol-1. We conclude that the protocol lengthens critically short telomeres and remodels the relative proportions of circulating leukocytes of CMV þ subjects toward the more ''youthful'' profile of CMV À subjects. Controlled randomized trials are planned to assess TA-65 Ò -specific effects in humans.
Potential of telomerase activation in extending health span and longevity
Current Opinion in Cell Biology, 2012
The progressive increase in the elderly population worldwide has resulted in higher numbers of individuals affected by age-associated diseases, such as neurodegenerative and heart diseases, metabolic impairment, or cancer, with the subsequent burden for national health systems. Therapeutic interventions aimed to increase the quality of life at advanced age are visualized as important demands for the future, both at the level of individuals and society. Novel advances in telomerase function from several independent laboratories have resulted in potential new therapeutic strategies which appear as promising new venues to prevent cellular and tissue dysfunction and organismal decline, thereby increasing the so-called "health span". Here, we analyze these recent advances.