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 R Madeddu; Giuseppe Passarino; Carmine Vecchione; Giuseppina Rose; Annibale A. Puca

doi:10.18632/aging.102209

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 R Madeddu, Giuseppe Passarino, Carmine Vecchione, Giuseppina Rose, Annibale A. Puca

Bristol Medical School (THS)

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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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.

Original language	English
Pages (from-to)	6555-6568
Number of pages	14
Journal	Aging
Volume	11
Issue number	16
DOIs	https://doi.org/10.18632/aging.102209
Publication status	Published - 28 Aug 2019

Keywords

BPIFB4
frailty
aging
Longevity-Associated Variant-LAV
survival

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10.18632/aging.102209

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Malavolta, M., Dato, S., Villa, F., De Rango, F., Iannone, F., Ferrario, A., Maciag, A., Ciaglia, E., D'amato, A., Carrizzo, A., Basso, A., Orlando, F., Provinciali, M., Madeddu, P. R., Passarino, G., Vecchione, C., Rose, G., & Puca, A. A. (2019). LAV-BPIFB4 associates with reduced frailty in humans and its transfer prevents frailty progression in old mice. Aging, 11(16), 6555-6568. https://doi.org/10.18632/aging.102209

@article{49d4c9e9e84048a19c26a8e2178f0b7a,

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

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.",

keywords = "BPIFB4, frailty, aging, Longevity-Associated Variant-LAV, survival",

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

year = "2019",

month = aug,

day = "28",

doi = "10.18632/aging.102209",

language = "English",

volume = "11",

pages = "6555--6568",

journal = "Aging",

issn = "1945-4589",

publisher = "Impact Journals",

number = "16",

}

Malavolta, M, Dato, S, Villa, F, De Rango, F, Iannone, F, Ferrario, A, Maciag, A, Ciaglia, E, D'amato, A, Carrizzo, A, Basso, A, Orlando, F, Provinciali, M, Madeddu, PR, Passarino, G, Vecchione, C, Rose, G & Puca, AA 2019, 'LAV-BPIFB4 associates with reduced frailty in humans and its transfer prevents frailty progression in old mice.', Aging, vol. 11, no. 16, pp. 6555-6568. https://doi.org/10.18632/aging.102209

TY - JOUR

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 R

AU - Passarino, Giuseppe

AU - Vecchione, Carmine

AU - Rose, Giuseppina

AU - Puca, Annibale A.

PY - 2019/8/28

Y1 - 2019/8/28

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.

KW - BPIFB4

KW - frailty

KW - aging

KW - Longevity-Associated Variant-LAV

KW - survival

U2 - 10.18632/aging.102209

DO - 10.18632/aging.102209

M3 - Article (Academic Journal)

C2 - 31461407

VL - 11

SP - 6555

EP - 6568

JO - Aging

JF - Aging

SN - 1945-4589

IS - 16

ER -

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

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Keywords

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