REJUVENATION RESEARCH 2016
A NATURAL PRODUCT TELOMERASE ACTIVATOR LENGHTENS TELOMERES IN HUMANS
Laura Salvador, Gunasekaran Singaravelu, Calvin B. Harley, Peter Flom, Anitha Suram, and Joseph M. Raffaele - REJUVENATION RESEARCH, Volume XX, Number XX, 2016, Mary Ann Liebert, Inc.
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 telomeres in a statistically and possibly clinically significant manner.
Clinical Ophtalmology 2016
EVALUATION OF AN ORAL TRELOMERASE ACTIVATOR FOR EARLY AGE-RELATED MACULAR DEGENERATION STUDY
Published in Clinical Ophtamology, a PubMed-indexed and peer-reviewed journal [PMID: 268969760]
This study summarizes the findings on macular function from a randomized, double blind, placebo-controlled study of TA-65 in subjects with early age-related macular degeneration (AMD). Subjects taking TA-65(500 Units) significally improved their macular function aver 12 months period, whereas subjects inthe placebo group demonstrated decreased macular function. The findings suggest that TA-65 can improve macular function in a statiscally and possibly clinically significant manner..
FUNCTIONAL ASSESSMENT OF PHARMACOLOGICAL TELOMERASE ACTIVATORS IN HUMAN T CELLS
Molgora B, Bateman R., Sweeney G., Finger D., Dimler T., Effros R.B., Valenzuela H.F., Cells Journal. 2013 January 14: ISSN 2073—4409
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.
Aging Cell 2011
BLACKWELL PUBLISHING LTD / ANATOMICAL SOCIETY OF GREAT BRITAIN AND IRELAND
de Jesus BB, Schneeberger K, Vera E, Tegera A, Harley CB, Blasco MA. Aging Cell. 2011 August; 10(4): 604—621.
In this study, it is shown that a small-molecule activator of telomerase (TA-65) purified from the root of Astragalus membranaceus is capable of increasing average telomere length and decreasing the percentage of critically short telomeres and of DNA damage in haploinsufficient mouse embryonic fibroblasts (MEFs) that harbor critically short telomeres and a single copy of the telomerase RNA Terc gene (G3 Terc+/− MEFs). Importantly, TA-65 does not cause telomere elongation or rescue DNA damage in similarly treated telomerase-deficient G3 Terc−/− littermate MEFs. These results indicate that TA-65 treatment results in telomerase-dependent elongation of short telomeres and rescue of associated DNA damage, thus demonstrating that TA-65 mechanism of action is through the telomerase pathway. In addition, we demonstrate that TA-65 is capable of increasing mouse telomerase reverse transcriptase levels in some mouse tissues and elongating critically short telomeres when supplemented as part of a standard diet in mice. Finally, TA-65 dietary supplementation in female mice leads to an improvement of certain health-span indicators including glucose tolerance, osteoporosis and skin fitness, without significantly increasing global cancer incidence.
Harvard University Study 2011
THE FIRST DOCUMENTED AGE REVERSAL IN A MAMMAL: HARVARD UNIVERSITY STUDY SHOWS TELOMERASE ACTIVATION HELPS REVERSE THE AGING PROCESS
Jaskelioff M., Muller F.L., Paik J.H., Thomas E., Jiang S., Adams A.C., Sahin E., Kost-Alimova M., Protopopov A., Cadiñanos J., Horner J.W., Maratos-Flier E., Depinho R.A. Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature. 2011;469(7328):102-106.
According to a study published in the January 2011 issue of Nature journal, premature aging can be reversed by reactivating telomerase, the enzyme that lengthens telomeres.
The study, led by scientist Ronald DePinho, of the Dana-Farber Cancer Institute and Harvard Medical School in Boston, Massachusetts, offers the possibility that normal human aging could be slowed by activating the telomerase enzyme in cells where it has stopped working.
Researchers studied mice that were artificially aged by switching off the telomerase enzyme. The mice experienced:
- Weakened organs
- Grey hair
- Other age-related conditions
- Early death.
However, when the telomerase enzyme was switched back on, the mice became younger. Researchers saw a dramatic reversal in the signs and symptoms of aging with telomerase activation. Benefits included:
- Increased brain size
- Improved cognition
- Restoration of hair to a healthy sheen
- Restored fertility
- Recuperation of organs (spleen, liver, intestines)
The most important lesson learned from this study is that aged tissues, even ones in an advanced state of degeneration, retain a remarkable capacity to renew themselves and telomerase, when activated, can reverse certain aspects associated with aging.
“If you look at all those data together, you walk away with the idea that the loss of telomerase could be a very important instigator of the aging process,” according to Dr. DePinho.
Rejuvenation Research 2011
A NATURAL PRODUCT TELOMERASE ACTIVATOR AS PART OF A HEALTH MAINTENANCE PROGRAM
Harley CB, Liu W, Blasco MA, Vera E, Andrews WH, Briggs LA, Raffaele JM. Rejuvenation Research. 2011 February; 14(1): 45—56.
This one year human study showed improvements in telomere length and immune system biomarkers for people taking TA-65® capsules.
Study Model: 114 study participants were tested for telomere length and other biomarkers of the aging process both before and during one year of TA-65® administration, with checkpoints at baseline and at 3, 6, 9, and 12 months. Subjects took 5 to 10 mg of TA-65® per day. Health areas that were monitored included: blood count, immune system status and function, CMV status, kidney health, liver health, endocrine function, cholesterol balance, serum nutrient profile, glucose metabolism, inflammatory response, cardiovascular health, bone mineral density, dermal health, vision, and mental acuity, along with overall telomere length. No adverse events were reported by study subjects. The study also explored in vitro effects of TA-65®, utilizing cultured human neonatal keratinocytes and fetal fibroblasts.
Findings, Method of Action: Multiple in vitro experiments confirmed that TA-65® supports enhanced Telomerase-Activation in human cells. Of note is the fact that two and three-fold upregulating effects were seen at very low dosages. Meanwhile, untreated and vehicle-only (DMSO) treated cells showed very weak telomerase activity.
Findings, Health Effects: For the sake of studying TA-65®’s immune system effects, CMV status was noted for all participants at study start. CMV+ status is common enough to be considered a normal ubiquitous aspect of the aging process. Telomerase Activation positivity rate was relatively low with this group (54%) while mean age was 63, resulting in a study group that permitted separation of the effects of age and CMV status upon immune cell health.
The most significant findings in this one-year study were clear support for:
Decreased percentage of short telomeres
Healthy number of neutrophils among CMV+ subjects
Reduced percentage of non–functioning senescent cytotoxic T cells
Overall “more youthful” immune cell profile
Findings, Safety: No adverse events were seen, and there were no reports of unregulated cell growth during the study period. Some participants increased their dosage to 25 or 50 mg per day with no adverse effects.
Kaiser Permanente : Genetic Epidemiology Research 2011
GENETIC EPIDEMIOLOGY RESEARCH ON ADULT HEALTH AND AGING (GERA) STUDY
In the largest and most diverse study of aging to date, telomere length is being analyzed as a marker for age-related conditions. This genomic project, Genetic Epidemiology Research on Adult Health and Aging (GERA), aims to increase understanding of the genetic basis for a host of problems.
Funded by the National Institutes of Health, the project includes a wide scale genotyping project incorporating longitudinal clinical and health data. After adjusting for the range of demographic and behavioral factors that influence telomere length (age, sex, race, education, physical activity, BMI, smoking, and alcohol consumption), there was a significant relationship between individuals with the shortest telomere length and increased mortality.
“We found that individuals whose telomeres were in the shortest 10 percent were about 23 percent more likely to die in the three years following measurement of their telomeres, when compared with individuals whose telomeres were longer,” said lead study author Catherine Schaefer, director of the Kaiser Permanente research program on genes, environment and health.
The initial phase of the Kaiser Permanente/UCSF GERA study measured telomere length from saliva samples of more than 100,000 individuals in California, whose average age was 63 years old, and analyzed their historical health-related information from health surveys and electronic medical records.
The large cohort of 100,000 individuals demonstrated the importance of telomere length and health, and provides the foundation for continued studies on the pathways linking telomere biology and longevity.