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

Research output: Contribution to journalArticle

  • 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 R Madeddu
  • Giuseppe Passarino
  • Carmine Vecchione
  • Giuseppina Rose
  • Annibale A. Puca
Original languageEnglish
Pages (from-to)6555-6568
Number of pages14
JournalAging
Volume11
Issue number16
DOIs
DateAccepted/In press - 12 Aug 2019
DatePublished (current) - 28 Aug 2019

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.

    Research areas

  • BPIFB4, frailty, aging, Longevity-Associated Variant-LAV, survival

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via Impact Journals at https://www.aging-us.com/article/102209/text . Please refer to any applicable terms of use of the publisher.

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