Dataset Information

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.

SUBMITTER: Malavolta M

PROVIDER: S-EPMC6738439 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

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

Malavolta Marco M Dato Serena S Villa Francesco F Rango Francesco De F Iannone Francesca F Ferrario Anna A Maciag Anna A Ciaglia Elena E D'amato Antonio A Carrizzo Albino A Basso Andrea A Orlando Fiorenza F Provinciali Mauro M Madeddu Paolo P Passarino Giuseppe G Vecchione Carmine C Rose Giuseppina G Puca Annibale A AA

Aging 20190828 16

<h4>Background</h4>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 <i>BPIFB4</i> gene was found to correct endothelial dysfunction, one of the mechanisms underlying frailty, in aging mice whereas the <i>RV-BPIFB4</i> variant induced opposite effects. Thus, we newly hypothesize that, besides being associated with life expectancy, <i>BPIFB4</i> polymorphisms can p ...[more]

PMID: 31461407

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Project description:BackgroundThe binary diagnosis of Metabolic Syndrome(MetS) fails to accurately evaluate its severity, and the association between MetS severity and frailty progression remains inadequately elucidated. This study aims to clarify the relationship between the severity of MetS and the progression of frailty among the middle-aged and elderly population in China.MethodParticipants from the 2011-2018 China Health and Retirement Longitudinal Study(CHARLS) were included for a longitudinal analysis. The study employs a frailty index(FI) based on 32 health deficits to diagnose frailty and to assess FI trajectories. An age-sex-ethnicity-specific MetS scoring model (MetS score) was used to assess metabolic syndrome severity in Chinese adults. The Cumulative MetS score from 2012 to 2015 was calculated using the formula: (MetS score in wave 1 + MetS score in wave 3) / 2 × time(2015 - 2012). The association between MetS score, Cumulative MetS score, and the risk and trajectory of frailty were evaluated using Cox regression/logistic regression, and linear mixed models. Restricted Cubic Splines(RCS) models were utilized to detect potential non-linear associations.ResultsA higher MetS score was significantly associated with an increased risk of frailty(HR per 1 SD increase = 1.205; 95%CI: 1.14 to 1.273) and an accelerated FI trajectory(β per 1 SD increase = 0.113 per year; 95%CI: 0.075 to 0.15 per year). Evaluating changes in MetS score using a Cumulative MetS score indicated that each 1 SD increase in the Cumulative MetS score increased the risk of frailty by 22.2%(OR = 1.222; 95%CI: 1.133 to 1.319) and accelerated the rate of increase in FI(β = 0.098 per year; 95%CI: 0.058 to 0.138 per year). RCS model results demonstrated a dose-response curve relationship between MetS score and Cumulative MetS score with frailty risk. Stratified analysis showed consistency across subgroups. The interaction results indicate that in males and individuals under aged 60, MetS score may accelerate the increase in FI, a finding consistent across both models.ConclusionsOur findings underscore the positive correlation between the severity of MetS and frailty progression in the middle-aged and elderly, highlighting the urgent need for early identification of MetS and targeted interventions to reduce the risk of frailty.

Project description:Introduction:Frailty has been studied among the old population due to its association with negative outcomes. Presently there is no gold standard for measuring frailty, but several studies have used the frailty phenotype of Fried consisting of five components (weakness, slowness, unintentional weight loss, exhaustion, and low physical activity) that classify individuals as robust, pre-frail, or frail, depending on the number of components affected, respectively, zero, one or two, and three or more. This study aims to explore the specific contribution of each of these components to the frailty phenotype in a sample of oldest old community-dwelling individuals. Materials and Methods:Individuals aged 80+ years old living in the community (N = 142) participated in this study. Sociodemographic data (age, sex, educational level, and marital status) and Fried's frailty phenotype were collected. Descriptive analysis summarized sociodemographic information and the frailty components. Multiple correspondence analysis (MCA) was performed to detect and explore relationships between frailty's five components. Results:Participants had a mean age of 88.07 years (SD = 5.30 years) and were mainly women (73.9%). The majority of the sample were considered frail (71.8%) and pre-frail (24.7%), and the most recurrent component for both groups was slowness. From the MCA analysis, a two-dimension solution was considered the most adequate, with 53.47% of variance explained. Dimension 1 (32.21% of variance explained) showed weakness as the most discriminant component; dimension 2 (21.26% of variance explained) showed unintentional weight loss as the most discriminant component. Discussion:Results revealed a high number of pre-frail and frail participants. MCA proved to add an important understanding in examining the frailty phenotype; it revealed weakness as the most discriminant component for dimension 1, suggesting a high association with the frailty phenotype. MCA also identified two main features of frailty: one related with physical features (motor behavioral and grip strength) including weakness, low physical activity, and slowness; and the second related with intrinsic conditions (unintentional weight loss and exhaustion). Conclusion:This study corroborates the need of a differentiated approach to the frailty phenotype among very old individuals, bringing for consideration the specific influence of its components.

Dataset Information

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

Background

Conclusions

Publications

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

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