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Cya3.8

Cycloastragenol (TA-65) Research

Mostly mechanism / observational

9 peer-reviewed studies

What the evidence says

Mostly mechanism / observational

Most Cycloastragenol (TA-65) studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.

Most evidence is from medium-quality randomised trials published 2008–2026 with a typical study size of 117 participants.

Based on 9 studies · 2 RCTs · 117 total participants

Confidence

Low confidence

By outcome

Longevity & telomeresGenuinely activates telomerase and lengthened telomeres in one small RCT, but no human study shows extended lifespan or healthspan; telomere length is a surrogate marker · Ongoing
Mostly mechanism / observational8 studies
Immune & T-cell agingRemodeled the immune profile toward a younger pattern (fewer senescent T cells) in an open-label pilot, mostly in CMV-positive subjects; not confirmed in a controlled immune-endpoint trial · 3-6 months
Too few graded studies2 studies
Safety profile
Too few graded studies1 study

By the numbers

Pulled from 7 studies with measurable effects

Likely real effects

100%

across studies

People studied

117

typical study: 117 people

Strongest designs

0 pooled, 2 randomised

How long studies ran

3+ months

Populations Studied

Relatively healthy CMV-positive adults aged 53-871

Mechanistic / preclinical and clinical literature1

Experimental and clinical literature1

Adult/old mice1

Active research area

3 studies in the last 5 years

200820172026

1RCT2023

Bawamia B, Spray L, Wangsaputra VK, Bennaceur K, Vahabi S, Stellos K · Geroscience (2023)

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2Review2026

In plain English: The integration of A. membranaceus into evidence-based senile therapeutic strategies holds promise, but further mechanistic and clinical studies are required to optimize its safety and efficacy.

Abdelrahman ZR, Harb AA, Abdalla SS. · Biomolecules (2026)

Preclinical studies further support its protective effects against osteoporotic bone loss and photoaging-induced dermal degeneration.
This review summarizes the phytochemical composition of A. membranaceus and critically evaluates the mechanistic and therapeutic evidence underlying its anti-aging and anticancer actions on skin and bone tissues.
It also discusses the pharmacokinetic properties of A. membranaceus , including its absorption, bioavailability, and safety profile.

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3Telomere length change over 12 monthsRCTn=117 · medium study2016

In plain English: 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).

Salvador L, Singaravelu G, Harley CB, Flom P, Suram A, Raffaele JM · Rejuvenation Research (2016)

Randomized, double-blind, placebo-controlled trial of TA-65 over 12 months in 117 relatively healthy CMV-positive adults aged 53-87.
The low dose (250 U) significantly lengthened telomeres; the placebo group lost telomere length.
The high dose (1000 U) showed only a non-significant trend — more was not better.

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4Telomere-targeting in vascular aging (narrative review)Review2025

In plain English: This review provides an overview of the mechanistic basis underlying the anti-atherosclerotic effects of Astragalus-derived compounds and underscores critical key knowledge gaps.

Canale P, Andreassi MG · Journal of Cardiovascular Development and Disease (2025)

Recent review of astragaloside IV, cycloastragenol, and TA-65 for vascular aging and atherosclerosis.
Describes plausible anti-inflammatory, antioxidant, endothelial-protective and telomerase-modulating mechanisms.
Explicitly underscores critical knowledge gaps and the need to validate efficacy in clinical trials.

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5Anti-aging mechanisms of Astragalus / TA-65 (narrative review)Review2017

In plain English: A proprietary extract of the dried root of Astragalus membranaceus, called TA-65, was associated with a significant age-reversal effect in the immune system.

Liu P, Zhao H, Luo Y · Aging and Disease (2017)

Review of Astragalus and TA-65 across lifespan extension, vascular aging, brain aging, and cancer effects.
Notes that Astragalus components increase telomerase activity and have reported anticancer, antioxidant and immunoregulatory effects.
Frames TA-65's immune age-reversal as a finding within a still-experimental, mostly preclinical evidence base.

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6Short-telomere elongation and health-span markers in miceAnimal2011

In plain English: 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.

Bernardes de Jesus B, Schneeberger K, Vera E, Tejera A, Harley CB, Blasco MA · Aging Cell (2011)

TA-65 (purified from Astragalus root) elongated critically short telomeres and reduced DNA damage in mouse cells via a telomerase-dependent mechanism.
The effect was absent in telomerase-deficient cells, pinning the action to the telomerase pathway.
Dietary TA-65 improved some health-span markers (glucose tolerance, osteoporosis, skin) in mice.

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7Immune-cell remodeling and short-telomere percentageOpen-Label2011

In plain English: 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.

Harley CB, Liu W, Blasco M, Vera E, Andrews WH, Briggs LA, Raffaele JM · Rejuvenation Research (2011)

Likely real

Open-label first-year analysis of the commercial TA-65 'PattonProtocol-1' (TA-65 10-50 mg/day plus a supplement pack), focused on the immune system.
Declines in senescent cytotoxic CD8+/CD28- T cells and natural killer cells, mostly in CMV-positive subjects.
Mean telomere length did not increase, but the percentage of short (<4 kbp) telomeres fell significantly (p = 0.037).

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8Telomerase activation and antiviral T-cell functionIn Vitro2008

In plain English: Exposure of CD8(+) T lymphocytes from HIV-infected human donors to a small molecule telomerase activator (TAT2) modestly retards telomere shortening, increases proliferative potential, and, importantly, enhances cytokine/chemokine production and antiviral activity.

Fauce SR, Jamieson BD, Chin AC, Mitsuyasu RT, Parish ST, Ng HL, Kitchen CM, Yang OO, Harley CB, Effros RB · Journal of Immunology (2008)

Foundational mechanism paper: the cycloastragenol-derived activator TAT2 modestly slowed telomere shortening in human CD8+ T cells ex vivo.
It increased proliferative potential and enhanced antiviral cytokine/chemokine production.
The enhanced antiviral effect was abolished by a specific telomerase inhibitor, confirming the action is through telomerase.

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9Telomerase activation in neuronal cellsIn Vitro2014

In plain English: CAG stimulates telomerase activity in human neonatal keratinocytes and rat neuronal cells, and induces CREB activation followed by tert and bcl2 expression.

Ip FC, Ng YP, An HJ, Dai Y, Pang HH, Hu YQ, Chin AC, Harley CB, Wong YH, Ip NY · Neurosignals (2014)

Cycloastragenol (the aglycone of astragaloside IV) stimulated telomerase activity in human keratinocytes and rat neurons.
It activated CREB and induced telomerase reverse transcriptase (TERT) expression in cortical neurons.
Oral cycloastragenol attenuated depression-like behavior in mice over 7 days.

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View in Research Library

Cycloastragenol (TA-65) Research

Mostly mechanism / observational

By the numbers

Activation of telomerase by TA-65 enhances immunity and reduces inflammation post myocardial infarction.

Astragalus membranaceus Has Potential Anti-Aging and Anticancer Effects on Skin and Bone

A Natural Product Telomerase Activator Lengthens Telomeres in Humans: A Randomized, Double Blind, and Placebo Controlled Study.

Targeting Telomere Shortening in Vascular Aging and Atherosclerosis: Therapeutic Promise of Astragalus membranaceus.

Anti-Aging Implications of Astragalus Membranaceus (Huangqi): A Well-Known Chinese Tonic.

The telomerase activator TA-65 elongates short telomeres and increases health span of adult/old mice without increasing cancer incidence.

A natural product telomerase activator as part of a health maintenance program.

Telomerase-based pharmacologic enhancement of antiviral function of human CD8+ T lymphocytes.

Cycloastragenol is a potent telomerase activator in neuronal cells: implications for depression management.