September 11, 2010

Sierra Sciences Have Successfully Lengthened Telomeres Which Could Be Used to Extend Human Lifespan

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Sierra Sciences, in collaboration with TA Sciences, Geron Corporation, PhysioAge, and the Spanish National Cancer Research Center (CNIO), has announced the first compound ever discovered that activates the enzyme telomerase in the human body - a critical prerequisite for technology that could arrest or reverse the aging process in humans. This compound is a natural product derived nutraceutical known as TA-65. These findings appear as a research article entitled 'A natural product telomerase activator as part of a health maintenance program,' published September 7, 2010 in the peer-reviewed journal Rejuvenation Research.

The full article is here

Another study indicates that the effects of an aging population have been overestimated by five times.

Researchers discovered that TA-65 was associated with a statistically significant "age-reversal" effect in the immune system, in that it led to declines in the percentage of senescent cytotoxic T cells and natural killer cells after six to twelve months of use. In addition, further analysis with automated high-throughput confocal microscopy (HT-qFISH) revealed a decline in the percentage of white blood cells with critically short telomeres after twelve to eighteen months of use.

A 1-year health maintenance program consisting of a dietary supplement pack combined with a natural product–derived telomerase activator results in a decreased percentage of short leukocyte telomeres and remodeling of the relative proportions of the circulating leukocytes of CMV+ subjects toward the more “youthful” profile of CMV− subjects.

One of the strengths of our study is the low CMV-positivity rate (54%) in a relatively older population, which allows us to separate the effects of age and CMV status on immunosenescence. It also serves to mitigate one of our study's weaknesses—the lack of a control group—as the subjects were initially unaware of their CMV status and their subsequent knowledge is unlikely to have caused the segregation of many of the effects of the protocol by CMV status.

Several peer-reviewed publications have calculated that humans have a theoretical maximum lifespan of 125 years, but our health declines long before that. Many scientists believe that this limit on lifespan and decline in health is imposed by the gradual shortening of our telomeres, structures at the ends of our chromosomes that shorten with every cell division. Telomere shortening is thought to be the "clock of aging" contained within the human body. It has been repeatedly demonstrated that a human cell that does not undergo telomere shortening will divide indefinitely and is, by all available measurements, immortal.

The publication reports that TA-65 can cause telomerase, an enzyme that lengthens telomeres, to become active in human cells. Telomerase activation by TA-65 was shown to lengthen the shortest telomeres in humans, potentially extending human lifespan and healthspan. Telomerase activation is thought to be a keystone of future regenerative medicine and a necessary condition for clinical immortality.

Although TA-65 is probably too weak to completely arrest the aging process, it is the first telomerase activator recognized as safe for human use.

"We are on the cusp of curing aging," said William Andrews, Ph.D., co-author of this study and President and CEO of Sierra Sciences, LLC. "TA-65 is going to go down in history as the first supplement you can take that doesn't merely extend your life a few years by improving your health, but actually affects the underlying mechanisms of aging. Better telomerase inducers will be developed in the coming years, but TA-65 is the first of a whole new family of telomerase-activating therapies that could eventually keep us young and healthy forever."

Telomerase activation has potential medical applications beyond extending human lifespan. Epidemiological studies have shown that short telomeres in humans are a risk factor for diseases including, among others, atherosclerosis, diabetes, Alzheimer's, and cancer.

The present study also reports encouraging news on the effect of TA-65 on the body's immune system. Infectious diseases lead to telomere shortening in the immune system, as immune cells divide to fight infections. Telomerase activation should prevent this telomere shortening and allow the body's immune system to fight a chronic infection indefinitely.

The present study on TA-65 lends support to this hypothesis. In individuals infected with CMV, a virus which prematurely ages the immune system and significantly reduces life expectancy, TA-65 caused an apparent "age reversal" of approximately 5 to 20 years based on one biomarker of immune aging.

For the same reason, telomerase activation is a potential treatment for AIDS. "We tend to see HIV turning into AIDS when the cells of the immune system develop critically short telomeres," said Andrews. "HIV can essentially cause the immune system to die of old age while the majority of the body is still young. A telomerase activator could theoretically prevent an HIV-positive individual from ever developing AIDS."

TA-65®, exclusively licensed to TA Sciences from Geron Corporation, is a >95% pure single chemical entity isolated from a proprietary extract of the dried root of Astragalus membranaceus and formulated into 5- to 10-mg capsules with inert excipients. Starting doses of 5–10mg/day were considered safe on the basis of historical usage of extracts. Some subjects increased their dosage after several months on the product to 25–50mg/day. Cumulative dose consumed during the year was recorded for each subject and used for preliminary dose–response analysis

TA-65® given orally in old mice showed similar reductions in percent cells with short telomeres and positive functional effects on tissues (Blasco et al., submitted) and preliminary dose–response analyses showed an increase in salutary effects with TA-65® doses up to 20–30mg per day average compared to the initial 5- to 10-mg per day dose (data not shown). Finally, analysis of additional biomarkers of aging in subjects on PattonProtocol-1 suggest improvements in the cardiovascular system, metabolism, and bone mineral density, which will be further studied and reported elsewhere. Independent randomized controlled studies with TA-65® alone are planned.

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®, 10–50mg 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® moderately activated telomerase in human keratinocytes, fibroblasts, and immune cells in culture; similar plasma levels of TA-65® 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+/CD28−) T cells (1.5, 4.4, 8.6, and 7.5% at 3, 6, 9, and 12 months, respectively; p=not significant [N.S.], 0.018, 0.0024, 0.0062) and natural killer cells at 6 and 12 months (p=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 (less tha 4000 base pairs) telomeres (p=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+ subjects toward the more “youthful” profile of CMV− subjects. Controlled randomized trials are planned to assess TA-65®-specific effects in humans.

Table of biomarkers

Table 2. Baseline Values for Selected Biomarkers, Relevant Blood/Immune Variables, and Relationship to Age

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