Cycloastragenol (TA-65) — Supplements
Triterpenoid from Astragalus root; the only supplement with human RCT evidence for telomere lengthening in immune cells via direct telomerase (TERT) activation.
Overview
Cycloastragenol (CAG) is a triterpenoid saponin derived by hydrolysis of astragaloside IV from Astragalus membranaceus root — a herb used in Traditional Chinese Medicine for over 2,000 years. It is the active ingredient in TA-65 (T.A. Sciences), the most studied telomerase-activating nutraceutical. Cycloastragenol activates telomerase reverse transcriptase (TERT) — the enzyme that extends telomere length — positioning it mechanistically upstream of cellular senescence, since critically short telomeres are a primary trigger of the p53/p21 senescence cascade. The primary human RCT (Salvador et al., 2016, Rejuvenation Research, n=117, randomized double-blind placebo-controlled) demonstrated significant telomere lengthening in CD4+/CD8+ T lymphocytes in CMV-positive adults aged 53–87 over 12 months. A separate RCT in 38 adults with early age-related macular degeneration showed improved macular sensitivity at 12 months versus placebo. Cycloastragenol also reduces senescent cell burden in immune cells, improves immune function biomarkers, and demonstrates anti-inflammatory activity. Unlike direct senolytics (which kill senescent cells after they form), cycloastragenol operates further upstream by preventing telomere shortening that triggers senescence — functioning as a senescence-prevention strategy rather than a senolytic.
Indications
- Immune senescence and immune system aging
- Telomere lengthening and cellular longevity (investigational)
- Age-related macular degeneration (AMD) — early stage
- Immune function preservation in aging
- Biological age reduction strategies
Mechanism of Action
Cycloastragenol transcriptionally upregulates TERT expression via interaction with telomerase activating elements (TAE) in the TERT promoter, increasing enzymatic activity in T lymphocytes, skin keratinocytes, and neuronal progenitor cells
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| Cycloastragenol (TA-65, T.A. Sciences) | 5–8 mg (250 Units) | Once to twice daily | TA-65 100U and 250U capsules are the only clinically validated forms; doses used in RCTs |
| Cycloastragenol (generic) | 25–100 mg | Once daily | Conversion from TA-65 Units to mg varies by product; generic products lack validated bioequivalence to TA-65 |
Safety & Contraindications
- Well tolerated in human trials to date — no serious adverse events reported in published RCTs
- Theoretical concern: telomerase activation could theoretically promote survival of pre-cancerous cells; no cancer signals in clinical trials to date, but long-term oncological safety data are limited
- Individuals with personal or strong family history of telomerase-driven cancers (dyskeratosis congenita, aplastic anemia, myelodysplastic syndrome) should avoid without oncology consultation
- CYP3A4 substrate and potential weak inhibitor — monitor for drug interactions in patients on CYP3A4-sensitive medications
- Avoid in pregnancy and breastfeeding — no safety data
- TA-65 is expensive (often $100–600/month) — cost-effectiveness relative to effect size is debated
- Product quality: only TA-65 (T.A. Sciences) has published clinical data; many cycloastragenol supplements lack validated purity and concentration