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Clinical Research 

        


  Functional Assessment of Pharmacological Telomerase Activators in Human T Cells

By T.A. Sciences ®





Molgora B, Bateman R., Sweeney G., Finger D., Dimler T., Effros R.B., Valenzuela H.F.,Cells Journal. 2013 January 14: ISSN 2073—4409
This human study demonstrates thatTA-65MD®nutritional supplements increase telomerase activity and proliferation in human CD4 and CD8 T cells. It highlights the importance of Telomerase Activation in relation to age-associated pathologies.

Study Method: CD4 and CD8 T cells from healthy subjects were treated with TA-65MD®. These samples were measured for telomerase activity 72 hours after primary stimulation. This process was repeated after 18-21 days for a second stimulation.
Findings, Method of Action: TA-65®increased telomerase activity in all subjects’ T cells during primary and secondary stimulations. The results show that TA-65®likely uses the MAPK pathway to activate telomerase. This result was observed in both CD4 and CD8 T cells but most significantly in CD8 T cells that were stimulated for the second time.
Findings, Health Effects:This study confirms that TA-65®rapidly induces telomerase activity, which other studies have linked to enhanced health span indicators, during an acute viral infection.

The most significant findings of this preliminary study are:

  • Clinical situations that require enhanced T cell telomerase activity should benefit from TA-65®
  • Acute viral infections protocols may benefit from the addition of TA-65®

Findings, Safety: No adverse side effects, interactions, or any other negative effects were reported during this study nor have any negative results been reported from any other study associated with TA-65®. No unregulated cell growth was observed during this study.


  


A Natural Product Telomerase Activator as Part of a Health Maintenance Program

By T.A. Sciences ®





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. The study confirmed TA-65®’s previously noted health effects and discovered other areas of whole health support that necessitate further research. The study also looked at thein vitroeffects of TA-65®on cultured human cells.

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: Multiplein vitroexperiments confirmed tha tTA-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®’simmune 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.



The Telomerase Activator, TA-65®, Elongates Short Telomeres and Increases Healthspan of Adult/Old Mice without Increasing Cancer Incidence

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De Jesus BB, Schneeberger K, Vera E, Tegera A, Harley CB, Blasco MA.Aging Cell. 2011 August; 10(4): 604—621.

This animal study looked at the effects of TA-65®and confirmed their mechanism of action, long-term effects, and safety.

Study Model: To confirm mechanism of action (through Telomerase Activation), mice that were haploinsufficient for the telomerase RNA Terc gene (Terc -/+) were treated, as well as mice that were bred for telomerase deficiency (Terc -/-). Both groups were confirmed to possess critically short telomeres at the study start. It was proposed that if the mechanism of action was indeed the activation of telomerase, only the group with a functioning Terc gene should respond to treatment; the telomerase-deficient group should experience no treatment effect.
The study tracked telomere length and other health indicators in the treatment groups and control group. No adverse incidents were seen.

Findings, Method of Action: Significant effects were seen in the Terc +/- group while no effects were seen in the Terc -/- group, indicating that TA-65®does indeed work through the Telomerase-Activation pathway.

Findings, Health Effects: In telomerase-proficient mice, TA-65® decreased the percentage of short telomeres and decreased the incidence of DNA compromise typically associated with a high percentage of short telomeres.TA-65® appeared to demonstrate a “preference” for activating telomerase in cells with the shortest telomeres, as indicated by a pronounced decrease in very short telomeres. This overall support for whole health on a cellular DNA level helps to explain the other key findings.TA-65® was found to influence several biomarkers for the aging process.* Notably, in the telomerase-proficient TA-65® treated group, researchers confirmed significant support for:

  • A decrease in the percentage of short telomeres
  • Lower incidence of DNA compromise typically associated with a high percentage of short telomeres
  • An overall enhanced Health span
  • Healthy glucose metabolism
  • Appropriate liver health and function
  • Healthy hair re-growth
  • Normal ongoing cellular repair and rejuvenation
  • Healthy bone density
  • Healthy blood profiles

TA-65® did not impact the mean or maximum longevity of the telomerase-proficient treatment group, but it did significantly influence the functional health span.

Findings, Safety: No adverse events were seen, and TA-65®did not cause any unregulated cell growth. This supports TA-65®‘s previously noted safe, transient effects on Telomerase Activation in healthy cells.



Genetic Epidemiology Research on Adult Health and Aging (GERA) Study

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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.


The First Documented Age Reversal in a Mammal: Harvard University Study shows Telomerase Activation Helps Reverse the Aging Process

By





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 ofNaturejournal, 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
  • Infertility
  • Grey hair
  • Dermatitis
  • 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.

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