• Open Access

The telomerase activator TA-65 elongates short telomeres and increases health span of adult/old mice without increasing cancer incidence

Authors

  • Bruno Bernardes de Jesus,

    1. Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre, Melchor Fernández Almagro 3, Madrid E-28029, Spain
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  • Kerstin Schneeberger,

    1. Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre, Melchor Fernández Almagro 3, Madrid E-28029, Spain
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  • Elsa Vera,

    1. Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre, Melchor Fernández Almagro 3, Madrid E-28029, Spain
    2. Life Length, Agustín de Betancourt 21, Madrid E-28003, Spain
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  • Agueda Tejera,

    1. Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre, Melchor Fernández Almagro 3, Madrid E-28029, Spain
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  • Calvin B. Harley,

    1. Telome Health, Menlo Park, CA 94025, USA
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  • Maria A. Blasco

    1. Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre, Melchor Fernández Almagro 3, Madrid E-28029, Spain
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Maria A. Blasco, Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre, Melchor Fernández Almagro 3, Madrid, E-28029, Spain. Tel.: +34-917328034; fax: +34-917328028; e-mail:mblasco@cnio.es

Summary

Here, we show that a small-molecule activator of telomerase (TA-65) purified from the root of Astragalus membranaceus is capable of increasing average telomere length and decreasing the percentage of critically short telomeres and of DNA damage in haploinsufficient mouse embryonic fibroblasts (MEFs) that harbor critically short telomeres and a single copy of the telomerase RNA Terc gene (G3 Terc+/− MEFs). Importantly, TA-65 does not cause telomere elongation or rescue DNA damage in similarly treated telomerase-deficient G3 Terc−/− littermate MEFs. These results indicate that TA-65 treatment results in telomerase-dependent elongation of short telomeres and rescue of associated DNA damage, thus demonstrating that TA-65 mechanism of action is through the telomerase pathway. In addition, we demonstrate that TA-65 is capable of increasing mouse telomerase reverse transcriptase levels in some mouse tissues and elongating critically short telomeres when supplemented as part of a standard diet in mice. Finally, TA-65 dietary supplementation in female mice leads to an improvement of certain health-span indicators including glucose tolerance, osteoporosis and skin fitness, without significantly increasing global cancer incidence.

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