LAV-BPIFB4 associates with reduced frailty in humans and its transfer prevents frailty progression in old mice

Marco Malavolta, Serena Dato, Francesco Villa, Francesco De Rango, Francesca Iannone, Anna Ferrario, Anna Maciag, Elena Ciaglia, Antonio D'amato, Albino Carrizzo, Andrea Basso, Fiorenza Orlando, Mauro Provinciali, Paolo Madeddu, Giuseppe Passarino, Carmine Vecchione, Giuseppina Rose, Annibale A. Puca

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)6555-6568
Number of pages14
JournalAging
Volume11
Issue number16
DOIs
Publication statusPublished - Jan 1 2019

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Haplotypes
Genes
Life Expectancy
Genetic Markers
Italy
Population

Keywords

  • Aging
  • BPIFB4
  • Frailty
  • Longevity-Associated Variant-LAV
  • Survival

ASJC Scopus subject areas

  • Ageing
  • Cell Biology

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LAV-BPIFB4 associates with reduced frailty in humans and its transfer prevents frailty progression in old mice. / Malavolta, Marco; Dato, Serena; Villa, Francesco; De Rango, Francesco; 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.

In: Aging, Vol. 11, No. 16, 01.01.2019, p. 6555-6568.

Research output: Contribution to journalArticle

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abstract = "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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T1 - LAV-BPIFB4 associates with reduced frailty in humans and its transfer prevents frailty progression in old mice

AU - Malavolta, Marco

AU - Dato, Serena

AU - Villa, Francesco

AU - De Rango, Francesco

AU - Iannone, Francesca

AU - Ferrario, Anna

AU - Maciag, Anna

AU - Ciaglia, Elena

AU - D'amato, Antonio

AU - Carrizzo, Albino

AU - Basso, Andrea

AU - Orlando, Fiorenza

AU - Provinciali, Mauro

AU - Madeddu, Paolo

AU - Passarino, Giuseppe

AU - Vecchione, Carmine

AU - Rose, Giuseppina

AU - Puca, Annibale A.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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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