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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2019
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.
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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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