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

EMBO Molecular Medicine
Bruno Bernardes de JesusMaria A Blasco

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 longevi...Continue Reading

Associated Clinical Trials

References

Mar 1, 1989·Journal of Gerontology·H ShimokataR Andres
Jan 1, 1986·Experimental Aging Research·D K Ingram, M A Reynolds
Mar 1, 1982·Metabolism: Clinical and Experimental·C J Bailey, P R Flatt
Jan 1, 1997·International Review of Neurobiology·J Doyon
May 24, 2001·Proceedings of the National Academy of Sciences of the United States of America·K FlurkeyD E Harrison
May 17, 2002·Current Opinion in Neurobiology·Okihide HikosakaHiroyuki Nakahara
May 30, 2002·Proceedings of the National Academy of Sciences of the United States of America·Steven E ArtandiRonald A DePinho
Aug 23, 2002·Proceedings of the National Academy of Sciences of the United States of America·Guang-Ping GaoJames M Wilson
Sep 21, 2002·Molecular and Cellular Biology·Eva González-SuárezMaría A Blasco
Dec 17, 2002·Nature·Martin HolzenbergerYves Le Bouc
Jan 25, 2003·Science·Matthias BlüherC Ronald Kahn
Sep 19, 2003·Bone·Virginia L FergusonSteven J Simske
Apr 9, 2005·The New England Journal of Medicine·Hiroki YamaguchiNeal S Young
Apr 15, 2005·Nature·Tannishtha Reya, Hans Clevers
Jul 23, 2005·Science·Ignacio FloresMaría A Blasco
Apr 4, 2006·EMBO Reports·Isabel García-CaoManuel Serrano
May 23, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Katsuya InagakiHiroyuki Nakai
Aug 2, 2006·Molecular and Cellular Biology·Ignacio FloresMaría A Blasco
Sep 8, 2006·Nature·Janakiraman KrishnamurthyNorman E Sharpless
Dec 15, 2006·Nature·Leonard Guarente
Mar 30, 2007·The New England Journal of Medicine·Mary Y ArmaniosJames E Loyd
Apr 27, 2007·Proceedings of the National Academy of Sciences of the United States of America·Kalliopi D TsakiriChristine Kim Garcia
Jul 20, 2007·Nature·Ander MatheuManuel Serrano
Jul 31, 2007·Cell·Manuel ColladoManuel Serrano
Feb 12, 2008·Current Protocols in Molecular Biology·Sami HeikkinenJohan Auwerx
Feb 20, 2008·Genes & Development·Ignacio FloresMaría A Blasco
Apr 17, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Carmela ZincarelliJoseph E Rabinowitz

❮ Previous
Next ❯

Citations

Oct 2, 2012·Cell Reports·Elsa VeraMaria A Blasco
Jul 24, 2013·Trends in Genetics : TIG·Bruno Bernardes de Jesus, Maria A Blasco
Aug 11, 2012·Rejuvenation Research·Andrew R Mendelsohn, James W Larrick
Dec 6, 2012·Current Opinion in Oncology·Branca Pereira, Miguel G Ferreira
Oct 12, 2012·Biology Letters·Annaliese K BeeryElissa S Epel
Nov 16, 2013·Biochemistry. Biokhimii︠a︡·J J Mitteldorf
Nov 16, 2013·Biochemistry. Biokhimii︠a︡·J J Mitteldorf
Jan 29, 2014·Molekuliarnaia biologiia·N A KovalenkoT F Kovalenko
Jun 8, 2013·Disease Models & Mechanisms·Monique AnchelinMaría L Cayuela
Jan 26, 2013·PLoS Genetics·Catarina M HenriquesMiguel Godinho Ferreira
May 7, 2013·PloS One·Virginia BoccardiGiuseppe Paolisso
Oct 16, 2012·Current Pharmaceutical Design·Jennifer P Chou, Rita B Effros
Sep 26, 2013·Epigenomics·Maria A Blasco
May 16, 2012·EMBO Molecular Medicine·Virginia Boccardi, Utz Herbig
Jan 5, 2014·Molecular Neurobiology·Deepak ChhanganiAmit Mishra
Feb 25, 2014·Ageing Research Reviews·Virginia Boccardi, Giuseppe Paolisso
Feb 5, 2014·Ageing Research Reviews·Shashi Kumar GuptaThomas Thum
Oct 8, 2013·The Journal of Nutrition, Health & Aging·S M Gasser, J le Coutre
Jan 1, 2012·Longevity & Healthspan·Elisabeth Schraml, Johannes Grillari
Oct 30, 2015·International Journal of Molecular Sciences·Maximina H Yun
Feb 13, 2016·Mutation Research·Peter Lenart, Lumir Krejci
Dec 15, 2015·Ageing Research Reviews·Sukhleen Kour, Pramod C Rath
Sep 14, 2014·Science China. Life Sciences·LiNa LiuQingPeng Kong
Feb 3, 2015·Journal of Molecular and Cellular Cardiology·Simona GrecoFabio Martelli
Oct 31, 2012·Aging Cell·Antonia Tomás-LobaMaria A Blasco
Nov 20, 2012·Social and Personality Psychology Compass·Eli Puterman, Elissa Epel
Jun 12, 2013·Cell·Carlos López-OtínGuido Kroemer
Feb 6, 2014·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Pierre J Marie
Aug 26, 2015·Ageing Research Reviews·Mirre J P Simons
Sep 11, 2012·Current Opinion in Cell Biology·José M P Freije, Carlos López-Otín
Sep 27, 2012·Brain, Behavior, and Immunity·Janice K Kiecolt-GlaserElizabeth Blackburn
Jan 4, 2013·Experimental Gerontology·Sylvia WeilnerJohannes Grillari
Apr 22, 2015·Ageing Research Reviews·Virginia BoccardiPatrizia Mecocci

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
chromosomal aberrations
transfection
PCR
X-ray
ELISA

Software Mentioned

Image J
Definiens Developer Cell
GraphPad Prism

Related Concepts

Related Feeds

Cell-Type-Specific Viral Vectors (ASM)

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Cell-Type Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Cell-Type-Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.