Activation of telomerase by TA-65 enhances immunity and reduces inflammation post myocardial infarction: original article
Myocardial infarction (MI) accelerates immune ageing characterised by lymphopenia, expansion of terminally differentiated CD8+ T-lymphocytes (CD8+ TEMRA) and inflammation. Pre-clinical data showed that TA-65, an oral telomerase activator, reduced immune ageing and inflammation after MI. We conducted...
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| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
22 April 2023
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| In: |
GeroScience
Year: 2023, Volume: 45, Issue: 4, Pages: 2689-2705 |
| ISSN: | 2509-2723 |
| DOI: | 10.1007/s11357-023-00794-6 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1007/s11357-023-00794-6 Verlag, kostenfrei, Volltext: https://link.springer.com/article/10.1007/s11357-023-00794-6 
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| Author Notes: | Bilal Bawamia, Luke Spray, Vincent K. Wangsaputra, Karim Bennaceur, Sharareh Vahabi, Konstantinos Stellos, Ehsan Kharatikoopaei, Emmanuel Ogundimu, Chris P Gale, Bernard Keavney, Rebecca Maier, Helen Hancock, Gavin Richardson, David Austin, Ioakim Spyridopoulos |
| Summary: | Myocardial infarction (MI) accelerates immune ageing characterised by lymphopenia, expansion of terminally differentiated CD8+ T-lymphocytes (CD8+ TEMRA) and inflammation. Pre-clinical data showed that TA-65, an oral telomerase activator, reduced immune ageing and inflammation after MI. We conducted a double blinded randomised controlled pilot trial evaluating the use of TA-65 to reduce immune cell ageing in patients following MI. Ninety MI patients aged over 65 years were randomised to either TA-65 (16 mg daily) or placebo for 12 months. Peripheral blood leucocytes were analysed by flow cytometry. The pre-defined primary endpoint was the proportion of CD8+ T-lymphocytes which were CD8+ TEMRA after 12 months. Secondary outcomes included high-sensitivity C-reactive protein (hsCRP) levels. Median age of participants was 71 years. Proportions of CD8+ TEMRA did not differ after 12 months between treatment groups. There was a significant increase in mean total lymphocyte count in the TA-65 group after 12 months (estimated treatment effect: + 285 cells/μl (95% CI: 117-452 cells/ μ l, p < 0.004), driven by significant increases from baseline in CD3+, CD4+, and CD8+ T-lymphocytes, B-lymphocytes and natural killer cells. No increase in lymphocyte populations was seen in the placebo group. At 12 months, hsCRP was 62% lower in the TA-65 group compared to placebo (1.1 vs. 2.9 mg/L). Patients in the TA-65 arm experienced significantly fewer adverse events (130 vs. 185, p = 0.002). TA-65 did not alter CD8+ TEMRA but increased all major lymphocyte subsets and reduced hsCRP in elderly patients with MI after 12 months. |
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| Item Description: | Gesehen am 01.02.2024 |
| Physical Description: | Online Resource |
| ISSN: | 2509-2723 |
| DOI: | 10.1007/s11357-023-00794-6 |