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Lookup NU author(s): Dr Bilal Bawamia, Dr Luke Spray, Vincent Wangsaputra, Dr Karim Bennaceur, Dr Sharareh Vahabi, Professor Konstantinos StellosORCiD, Dr Ehsan Kharatikoopaei, Professor Bernard Keavney, Rebecca Maier, Professor Helen HancockORCiD, Professor Gavin RichardsonORCiD, Dr David Austin, Professor Ioakim SpyridopoulosORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
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.
Author(s): Bawamia B, Spray L, Wangsaputra VK, Bennaceur K, Vahabi S, Stellos K, Kharatikoopaei E, Ogundimu E, Gale CP, Keavney B, Maier R, Hancock H, Richardson GD, Austin D, Spyridopoulos I
Publication type: Article
Publication status: Published
Journal: GeroScience
Year: 2023
Volume: 45
Pages: 2689-2705
Print publication date: 22/04/2023
Online publication date: 22/04/2023
Acceptance date: 06/04/2023
Date deposited: 25/04/2023
ISSN (electronic): 2509-2723
Publisher: Springer
URL: https://doi.org/10.1007/s11357-023-00794-6
DOI: 10.1007/s11357-023-00794-6
Data Access Statement: Data are available upon request and following approval by the trial steering committee
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