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Background <p>TA-65®, a telomerase-activating compound derived from <i>Astragalus membranaceus</i>, has garnered interest for its potential to modulate cellular aging. However, its mechanistic efficacy and long-term toxicological profile remain inadequately synthesized.</p> Methods <p>This PRISMA-guided meta-analysis evaluated 8 randomized controlled trials (RCTs, n = 750 participants; mean age 63.3&#xa0;years) assessing TA-65’s effects on telomere dynamics, functional aging indices, and safety outcomes. Primary outcomes included leukocyte telomere length (LTL) measured by Southern blot or qPCR/or flow-FISH; secondary outcomes encompassed frailty metrics (SPPB, grip strength, 6MWT), inflammatory markers (hs-CRP, IL-6), and adverse events (CTCAE v5.0). Statistical synthesis employed random-effects models (RevMan 5.3), subgroup analyses, and GRADE evidence grading.</p> Results <p>TA-65 supplementation induced moderate telomere elongation (SMD = 0.47, 95% CI: 0.31–0.62; p &lt; 0.00001), with amplified effects in adults &gt; 60&#xa0;years (SMD = 0.63 vs. 0.36; p = 0.03). Industry-funded trials reported inflated efficacy (SMD = 0.63 vs. 0.40; p = 0.03). Critically, telomere elongation did not translate to functional improvements in frailty (SMD = 0.09, p = 0.15) or inflammation (CRP/IL-6 SMD =  − 0.11, p = 0.07), revealing a telomere-function disconnect. Safety analysis (n = 487) identified mild gastrointestinal toxicity (12.4% incidence; nausea: 7.1%, abdominal discomfort: 5.3%) but no severe adverse events (e.g., oncogenesis) over 12&#xa0;months. Dose–response relationships (10–50&#xa0;mg/day) and measurement-method variations were non-significant (p &gt; 0.05).</p> Conclusions <p>While TA-65 demonstrates telomerase-activating efficacy, particularly in older adults, its failure to improve functional aging metrics underscores limitations of unimodal biomarker targeting. The absence of dose-dependent toxicity or short-term oncogenic risk is notable, yet long-term carcinogenic potential remains unaddressed. Rigorous, independent trials must evaluate TA-65’s chronic toxicity, telomere-independent mechanisms, and utility within multidimensional aging frameworks. Clinical application may consider older adults with immunosenescence, incorporating safety surveillance for gastrointestinal and oncological endpoints.</p> Graphical Abstract <p>This graphical abstract summarizes the design, key findings, and conclusion of our meta-analysis on TA-65's effects on telomere length and functional aging outcomes.</p> <p></p>

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Effects of TA-65 on telomere length, functional outcomes, and inflammation: a systematic review and meta-analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月25日

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  • Xiaojuan Su,
  • Cheng Wang,
  • Zhixian Gou,
  • Yi Qu

摘要

Background

TA-65®, a telomerase-activating compound derived from Astragalus membranaceus, has garnered interest for its potential to modulate cellular aging. However, its mechanistic efficacy and long-term toxicological profile remain inadequately synthesized.

Methods

This PRISMA-guided meta-analysis evaluated 8 randomized controlled trials (RCTs, n = 750 participants; mean age 63.3 years) assessing TA-65’s effects on telomere dynamics, functional aging indices, and safety outcomes. Primary outcomes included leukocyte telomere length (LTL) measured by Southern blot or qPCR/or flow-FISH; secondary outcomes encompassed frailty metrics (SPPB, grip strength, 6MWT), inflammatory markers (hs-CRP, IL-6), and adverse events (CTCAE v5.0). Statistical synthesis employed random-effects models (RevMan 5.3), subgroup analyses, and GRADE evidence grading.

Results

TA-65 supplementation induced moderate telomere elongation (SMD = 0.47, 95% CI: 0.31–0.62; p < 0.00001), with amplified effects in adults > 60 years (SMD = 0.63 vs. 0.36; p = 0.03). Industry-funded trials reported inflated efficacy (SMD = 0.63 vs. 0.40; p = 0.03). Critically, telomere elongation did not translate to functional improvements in frailty (SMD = 0.09, p = 0.15) or inflammation (CRP/IL-6 SMD =  − 0.11, p = 0.07), revealing a telomere-function disconnect. Safety analysis (n = 487) identified mild gastrointestinal toxicity (12.4% incidence; nausea: 7.1%, abdominal discomfort: 5.3%) but no severe adverse events (e.g., oncogenesis) over 12 months. Dose–response relationships (10–50 mg/day) and measurement-method variations were non-significant (p > 0.05).

Conclusions

While TA-65 demonstrates telomerase-activating efficacy, particularly in older adults, its failure to improve functional aging metrics underscores limitations of unimodal biomarker targeting. The absence of dose-dependent toxicity or short-term oncogenic risk is notable, yet long-term carcinogenic potential remains unaddressed. Rigorous, independent trials must evaluate TA-65’s chronic toxicity, telomere-independent mechanisms, and utility within multidimensional aging frameworks. Clinical application may consider older adults with immunosenescence, incorporating safety surveillance for gastrointestinal and oncological endpoints.

Graphical Abstract

This graphical abstract summarizes the design, key findings, and conclusion of our meta-analysis on TA-65's effects on telomere length and functional aging outcomes.