Abstract
BackgroundBrain-derived neurotrophic factor (BDNF) has been implicated in cognitive performance and the modulation of several metabolic parameters in some disease models, but its potential roles in successful aging remain unclear. We herein sought to define the putative correlation between BDNF Val66Met and several metabolic risk factors including BMI, blood pressure, fasting plasma glucose (FPG) and lipid levels in a long-lived population inhabiting Hongshui River Basin in Guangxi.MethodsBDNF Val66Met was typed by ARMS-PCR for 487 Zhuang long-lived individuals (age ≥ 90, long-lived group, LG), 593 of their offspring (age 60–77, offspring group, OG) and 582 ethnic-matched healthy controls (aged 60–75, control group, CG) from Hongshui River Basin. The correlations of genotypes with metabolic risks were then determined.ResultsAs a result, no statistical difference was observed on the distribution of allelic and genotypic frequencies of BDNF Val66Met among the three groups (all P > 0.05) except that AA genotype was dramatically higher in females than in males of CG. The HDL-C level of A allele (GA/AA genotype) carriers was profoundly lower than was non-A (GG genotype) carriers in the total population and the CG (P = 0.009 and 0.006, respectively), which maintained in females, hyperglycemic and normolipidemic subgroup of CG after stratification by gender, BMI, glucose and lipid status. Furthermore, allele A carriers, with a higher systolic blood pressure, exhibited 1.63 folds higher risk than non-A carriers to be overweight in CG (OR = 1.63, 95% CI: 1.05 - 2.55, P = 0.012). Multiple regression analysis displayed that the TC level of LG reversely associated with BDNF Val66Met genotype.ConclusionsThese data suggested that BDNF 66Met may play unfavorable roles in blood pressure and lipid profiles in the general population in Hongshui River area which might in part underscore their poorer survivorship versus the successful aging individuals and their offspring.
Highlights
Brain-derived neurotrophic factor (BDNF) has been implicated in cognitive performance and the modulation of several metabolic parameters in some disease models, but its potential roles in successful aging remain unclear
After adjustment for age and sex, diastolic blood pressure (DBP), Total cholesterol (TC), and low density lipoprotein cholesterol (LDL-C) were found to be higher while fasting plasma glucose (FPG) was lower in lived group (LG) as compared with offspring group (OG) and/or control group (CG)
Instead of finding salutary genotypes of BDNF gene which may account in part for better preservation of health in the oldest olds and their offspring, we noted unexpectedly an overrepresentation of BDNF 66 Met and its adverse correlation with several metabolic parameters in the general population living in the same area as the long-lived families, which can explain why local residents have higher morbidity and mortality as compared to individuals with exceptional longevity
Summary
Brain-derived neurotrophic factor (BDNF) has been implicated in cognitive performance and the modulation of several metabolic parameters in some disease models, but its potential roles in successful aging remain unclear. Multiple lines of evidence have implicated that BDNF is stimulating for nerve growth and survival, and exert nonneurotrophic effects over blood pressure, glucose, lipid and energy homeostasis in humans and model animals via central pathways involved in appetite regulation and energy expenditure [7,8,9,10] It suppresses food intake, facilitates glucose uptake in the brain, reduces hepatic glucose production and converts white fat into brown fat in adipose tissue, leading to energy dissipation, lowered blood glucose and a lean phenotype; its downregulation in BDNF knockout mice and diabetic patients is associated with hyperphagic behavior, elevated blood glucose and cholesterol, and obese phenotype [10]. It is reasonable to assume that long-lived individuals with better cognition might harbor beneficial BDNF genotypes and corresponding advantage profiles of metabolic parameters
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