Research Paper|Volume 11, Issue 16|pp 6555—6568

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

Marco Malavolta¹, Serena Dato², Francesco Villa³, Francesco De Rango², Francesca Iannone², Anna Ferrario³, Anna Maciag³, Elena Ciaglia⁴, Antonio D'amato⁵, Albino Carrizzo⁵, Andrea Basso¹, Fiorenza Orlando⁶, Mauro Provinciali^1,⁶, Paolo Madeddu⁷, Giuseppe Passarino², Carmine Vecchione^4,⁵, Giuseppina Rose², Annibale A Puca^3,⁴

¹Advanced Technology Center for Aging Research, Scientific Technological Area, IRCCS INRCA, Ancona, Italy
²Department of Biology, Ecology and Earth Sciences, University of Calabria, Rende, Italy
³IRCCS Multimedica, Cardiovascular Department, Milan, Italy
⁴Department of Medicine, University of Salerno, Baronissi, Italy
⁵IRCCS Neuromed, Department of Vascular Physiopathology, Pozzilli, Italy
⁶Experimental Animal Models for Aging Unit, Scientific Technological Area, IRCCS INRCA, Ancona, Italy
⁷Bristol Medical School (Translational Health Sciences), Bristol Heart Institute, University of Bristol, Bristol, UK

* Equal contribution

Received: June 27, 2019Accepted: August 12, 2019Published: August 28, 2019

https://doi.org/10.18632/aging.102209

Copyright © 2019 Malavolta et al. 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.

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.