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

Abstract

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.

Keywords: Anti-aging pharmacology; Biomarker-function disconnect; Industry bias; TA-65; Telomere paradox; Translational gerontology.