Effects of Human LAV-BPIFB4 Gene Therapy on the Epigenetic Clock and Health of Aged Mice
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Published:2023-03-30
Issue:7
Volume:24
Page:6464
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Giuliani Maria Elisa1ORCID, Barbi Veronica2ORCID, Bigossi Giorgia1ORCID, Marcozzi Serena1ORCID, Giacconi Robertina1ORCID, Cardelli Maurizio1, Piacenza Francesco1ORCID, Orlando Fiorenza3, Ciaglia Elena4ORCID, Cattaneo Monica5, Mongelli Alessia2ORCID, Gaetano Carlo2, Provinciali Mauro1ORCID, Puca Annibale Alessandro45ORCID, Malavolta Marco1ORCID
Affiliation:
1. Advanced Technology Center for Aging Research, IRCCS INRCA, 60121 Ancona, Italy 2. Laboratory of Epigenetics, Istituti Clinici Scientifici Maugeri IRCCS, Via Maugeri 10, 27100 Pavia, Italy 3. Experimental Animal Models for Aging Unit, Scientific Technological Area, IRCCS INRCA, 60015 Falconara Marittima, Italy 4. Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Via Salvatore Allende, 84081 Baronissi, Italy 5. Cardiovascular Research Unit, IRCCS MultiMedica, 20138 Milan, Italy
Abstract
The homozygous genotype of the Longevity-Associated Variant (LAV) in Bactericidal/Permeability-Increasing Fold-Containing Family B member 4 (BPIFB4) is enriched in long-living individuals of three independent populations and its genetic transfer in C57BL/6J mice showed a delay in frailty progression and improvement of several biomarkers of aging and multiple aspects of health. The C57BL/6J strain is a suitable model for studying therapies aimed at extending healthy aging and longevity due to its relatively short lifespan and the availability of aging biomarkers. Epigenetic clocks based on DNA methylation profiles are reliable molecular biomarkers of aging, while frailty measurement tools are used to evaluate overall health during aging. In this study, we show that the systemic gene transfer of LAV-BPIFB4 in aged C57BL/6J mice was associated with a significant reduction in the epigenetic clock-based biological age, as measured by a three CpG clock method. Furthermore, LAV-BPIFB4 gene transfer resulted in an improvement of the Vitality Score with a reduction in the Frailty Index. These findings further support the use of LAV-BPIFB4 gene therapy to induce beneficial effects on epigenetic mechanisms associated with aging and frailty in aged mice, with potential implications for future therapies to prevent frailty in humans.
Funder
Cariplo Foundation Italian Ministry of Health to IRCCS-INRCA
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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