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LAV-BPIFB4 associates with reduced frailty in humans and its transfer prevents frailty progression in old mice
Background: There is an increasing concern about age-related frailty because of the growing number of elderly people in the general population. The Longevity-Associated Variant (LAV) of the human BPIFB4 gene was found to correct endothelial dysfunction, one of the mechanisms underlying frailty, in a...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738439/ https://www.ncbi.nlm.nih.gov/pubmed/31461407 http://dx.doi.org/10.18632/aging.102209 |
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author | Malavolta, Marco Dato, Serena Villa, Francesco Rango, Francesco De Iannone, Francesca Ferrario, Anna Maciag, Anna Ciaglia, Elena D'amato, Antonio Carrizzo, Albino Basso, Andrea Orlando, Fiorenza Provinciali, Mauro Madeddu, Paolo Passarino, Giuseppe Vecchione, Carmine Rose, Giuseppina Puca, Annibale A. |
author_facet | Malavolta, Marco Dato, Serena Villa, Francesco Rango, Francesco De Iannone, Francesca Ferrario, Anna Maciag, Anna Ciaglia, Elena D'amato, Antonio Carrizzo, Albino Basso, Andrea Orlando, Fiorenza Provinciali, Mauro Madeddu, Paolo Passarino, Giuseppe Vecchione, Carmine Rose, Giuseppina Puca, Annibale A. |
author_sort | Malavolta, Marco |
collection | PubMed |
description | Background: There is an increasing concern about age-related frailty because of the growing number of elderly people in the general population. The Longevity-Associated Variant (LAV) of the human BPIFB4 gene was found to correct endothelial dysfunction, one of the mechanisms underlying frailty, in aging mice whereas the RV-BPIFB4 variant induced opposite effects. Thus, we newly hypothesize that, besides being associated with life expectancy, BPIFB4 polymorphisms can predict frailty. Aim and Results: Here we investigated if the BPIFB4 haplotypes, LAV, wild-type (WT) and RV, differentially associate with frailty in a cohort of 237 elderly subjects from Calabria region in Southern Italy. Moreover, we studied the effect of systemic adeno-associated viral vector-mediated LAV-BPIFB4 gene transfer on the progression of frailty in aging mice. We found an inverse correlation of the homozygous LAV-BPIFB4 haplotype with frailty in elderly subjects. Conversely, carriers of the RV-BPIFB4 haplotype showed an increase in the frailty status and risk of death. Moreover, in old mice, LAV-BPIFB4 gene transfer delayed frailty progression. Conclusions: These data indicate that specific BPIFB4 haplotypes could represent useful genetic markers of frailty. In addition, horizontal transfer of a healthy gene variant can attenuate frailty in aging organisms. |
format | Online Article Text |
id | pubmed-6738439 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-67384392019-09-16 LAV-BPIFB4 associates with reduced frailty in humans and its transfer prevents frailty progression in old mice Malavolta, Marco Dato, Serena Villa, Francesco Rango, Francesco De Iannone, Francesca Ferrario, Anna Maciag, Anna Ciaglia, Elena D'amato, Antonio Carrizzo, Albino Basso, Andrea Orlando, Fiorenza Provinciali, Mauro Madeddu, Paolo Passarino, Giuseppe Vecchione, Carmine Rose, Giuseppina Puca, Annibale A. Aging (Albany NY) Research Paper Background: There is an increasing concern about age-related frailty because of the growing number of elderly people in the general population. The Longevity-Associated Variant (LAV) of the human BPIFB4 gene was found to correct endothelial dysfunction, one of the mechanisms underlying frailty, in aging mice whereas the RV-BPIFB4 variant induced opposite effects. Thus, we newly hypothesize that, besides being associated with life expectancy, BPIFB4 polymorphisms can predict frailty. Aim and Results: Here we investigated if the BPIFB4 haplotypes, LAV, wild-type (WT) and RV, differentially associate with frailty in a cohort of 237 elderly subjects from Calabria region in Southern Italy. Moreover, we studied the effect of systemic adeno-associated viral vector-mediated LAV-BPIFB4 gene transfer on the progression of frailty in aging mice. We found an inverse correlation of the homozygous LAV-BPIFB4 haplotype with frailty in elderly subjects. Conversely, carriers of the RV-BPIFB4 haplotype showed an increase in the frailty status and risk of death. Moreover, in old mice, LAV-BPIFB4 gene transfer delayed frailty progression. Conclusions: These data indicate that specific BPIFB4 haplotypes could represent useful genetic markers of frailty. In addition, horizontal transfer of a healthy gene variant can attenuate frailty in aging organisms. Impact Journals 2019-08-28 /pmc/articles/PMC6738439/ /pubmed/31461407 http://dx.doi.org/10.18632/aging.102209 Text en Copyright © 2019 Malavolta et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY 3.0) License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Malavolta, Marco Dato, Serena Villa, Francesco Rango, Francesco De Iannone, Francesca Ferrario, Anna Maciag, Anna Ciaglia, Elena D'amato, Antonio Carrizzo, Albino Basso, Andrea Orlando, Fiorenza Provinciali, Mauro Madeddu, Paolo Passarino, Giuseppe Vecchione, Carmine Rose, Giuseppina Puca, Annibale A. LAV-BPIFB4 associates with reduced frailty in humans and its transfer prevents frailty progression in old mice |
title | LAV-BPIFB4 associates with reduced frailty in humans and its transfer prevents frailty progression in old mice |
title_full | LAV-BPIFB4 associates with reduced frailty in humans and its transfer prevents frailty progression in old mice |
title_fullStr | LAV-BPIFB4 associates with reduced frailty in humans and its transfer prevents frailty progression in old mice |
title_full_unstemmed | LAV-BPIFB4 associates with reduced frailty in humans and its transfer prevents frailty progression in old mice |
title_short | LAV-BPIFB4 associates with reduced frailty in humans and its transfer prevents frailty progression in old mice |
title_sort | lav-bpifb4 associates with reduced frailty in humans and its transfer prevents frailty progression in old mice |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738439/ https://www.ncbi.nlm.nih.gov/pubmed/31461407 http://dx.doi.org/10.18632/aging.102209 |
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