Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer by Bruno Bernardes de Jesus, Elsa Vera, Kerstin.

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Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer by Bruno Bernardes de Jesus, Elsa Vera, Kerstin Schneeberger, Agueda M. Tejera, Eduard Ayuso, Fatima Bosch, and Maria A. Blasco EMBO Mol Med. Volume 4(8): August 3, 2012 ©2012 by European Molecular Biology Organization

AAV9 ‐ mediated mTERT expression.A.Direct GFP fluorescence in shaved back skin of mice treated with the indicated vectors.B.Dark grey bars: fold change in mean ± SEM mTERT mRNA levels in AAV9 ‐ mTERT treated mice compared to AAV9 ‐ eGFP controls; light grey bars... Bruno Bernardes de Jesus et al. EMBO Mol Med. 2012;4: ©2012 by European Molecular Biology Organization

Delayed aging in AAV9 ‐ mTERT treated mice.A.Femur bone mineral density (BMD femur) at the indicated times post ‐ treatment with the indicated vectors. Bruno Bernardes de Jesus et al. EMBO Mol Med. 2012;4: ©2012 by European Molecular Biology Organization

Increased median and maximum longevity of AAV9 ‐ mTERT treated mice.A.Kaplan–Meier survival curves of the indicated mouse cohorts (50% males and 50% females). Bruno Bernardes de Jesus et al. EMBO Mol Med. 2012;4: ©2012 by European Molecular Biology Organization

AAV9 ‐ mTERT treatment decreases the abundance of short telomeres and increases active β ‐ catenin and cyclinD1 ‐ positive cells in AAV9 ‐ mTERT treated mice.A.Percentage of short telomeres (percentage of telomeres presenting an intensity below 50% of the mean inte... Bruno Bernardes de Jesus et al. EMBO Mol Med. 2012;4: ©2012 by European Molecular Biology Organization

Catalytic activity of mTERT is needed for increased healthspan and life ‐ span extension in AAV9 ‐ mTERT treated mice.A.Scheme of mTERT ‐ wt and mTERT ‐ DN, a catalytically inactive form of telomerase previously generated and described by us (see Materials and Meth... Bruno Bernardes de Jesus et al. EMBO Mol Med. 2012;4: ©2012 by European Molecular Biology Organization