Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer
Bernardes de Jesus, Bruno (Centro Nacional de Investigaciones Oncológicas)
Vera, Elsa (Centro Nacional de Investigaciones Oncológicas)
Schneeberger, Kerstin (Centro Nacional de Investigaciones Oncológicas)
Tejera, Agueda M. (Centro Nacional de Investigaciones Oncológicas)
Ayuso, Eduard (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Bosch i Tubert, Fàtima (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Blasco, María A (Centro Nacional de Investigaciones Oncológicas)

Data:	2012
Resum:	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.
Drets:	Aquest material està protegit per drets d'autor i/o drets afins. Podeu utilitzar aquest material en funció del que permet la legislació de drets d'autor i drets afins d'aplicació al vostre cas. Per a d'altres usos heu d'obtenir permís del(s) titular(s) de drets.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	AAV9 ; Aging ; Gene therapy ; Health span ; TERT ; SDG 3 - Good Health and Well-being
Publicat a:	EMBO Molecular Medicine, Vol. 4 Núm. 8 (2012) , p. 691-704, ISSN 1757-4684

DOI: 10.1002/emmm.201200245
PMID: 22585399

14 p, 719.6 KB

El registre apareix a les col·leccions:
Articles > Articles de recerca
Articles > Articles publicats