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
- 1 Advanced Technology Center for Aging Research, Scientific Technological Area, IRCCS INRCA, Ancona, Italy
- 2 Department of Biology, Ecology and Earth Sciences, University of Calabria, Rende, Italy
- 3 IRCCS Multimedica, Cardiovascular Department, Milan, Italy
- 4 Department of Medicine, University of Salerno, Baronissi, Italy
- 5 IRCCS Neuromed, Department of Vascular Physiopathology, Pozzilli, Italy
- 6 Experimental Animal Models for Aging Unit, Scientific Technological Area, IRCCS INRCA, Ancona, Italy
- 7 Bristol Medical School (Translational Health Sciences), Bristol Heart Institute, University of Bristol, Bristol, UK
Received: June 27, 2019 Accepted: August 12, 2019 Published: August 28, 2019
https://doi.org/10.18632/aging.102209How to Cite
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.