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Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer

Bruno Bernardes de Jesus, Elsa Vera, Kerstin Schneeberger, Agueda M. Tejera, Eduard Ayuso, Fatima Bosch, Maria A. Blasco

Author Affiliations

  1. Bruno Bernardes de Jesus1,
  2. Elsa Vera1,
  3. Kerstin Schneeberger1,
  4. Agueda M. Tejera1,
  5. Eduard Ayuso2,3,
  6. Fatima Bosch2,3 and
  7. Maria A. Blasco (mblasco{at}cnio.es) *,1
  1. 1Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Madrid, Spain
  2. 2Department of Biochemistry and Molecular Biology, Center of Animal Biotechnology and Gene Therapy (CBATEG), School of Veterinary Medicine. Universitat Autònoma de Barcelona, Bellaterra, Spain
  3. 3CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain
  1. *Tel: +34 91 732 8031; Fax: +34 91 732 8028
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Abstract

A major goal in aging research is to improve health during aging. In the case of mice, genetic manipulations that shorten or lengthen telomeres result, respectively, in decreased or increased longevity. Based on this, we have tested the effects of a telomerase gene therapy in adult (1 year of age) and old (2 years of age) mice. Treatment of 1‐ and 2‐year old mice with an adeno associated virus (AAV) of wide tropism expressing mouse TERT had remarkable beneficial effects on health and fitness, including insulin sensitivity, osteoporosis, neuromuscular coordination and several molecular biomarkers of aging. Importantly, telomerase‐treated mice did not develop more cancer than their control littermates, suggesting that the known tumorigenic activity of telomerase is severely decreased when expressed in adult or old organisms using AAV vectors. Finally, telomerase‐treated mice, both at 1‐year and at 2‐year of age, had an increase in median lifespan of 24 and 13%, respectively. These beneficial effects were not observed with a catalytically inactive TERT, demonstrating that they require telomerase activity. Together, these results constitute a proof‐of‐principle of a role of TERT in delaying physiological aging and extending longevity in normal mice through a telomerase‐based treatment, and demonstrate the feasibility of anti‐aging gene therapy.

See accompanying article http://dx.doi.org/10.1002/emmm.201200246

  • Received February 22, 2012.
  • Revision received March 29, 2012.
  • Accepted March 30, 2012.
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This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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