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遗传心血管风险和生活方式(包括红肉类摄入)对寿命的影响。

Impact on Longevity of Genetic Cardiovascular Risk and Lifestyle including Red Meat Consumption.

机构信息

Ecogenetics and Human Health Unit, Genetics Laboratory, Environmental Health Institute-ISAMB, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, Piso 1C 1649-028 Lisboa, Portugal.

Instituto de Investigação Bento da Rocha Cabral, Calçada Bento da Rocha Cabral 14, 1250-012 Lisboa, Portugal.

出版信息

Oxid Med Cell Longev. 2020 Jun 30;2020:1305413. doi: 10.1155/2020/1305413. eCollection 2020.

Abstract

BACKGROUND

Cardiovascular risk (CVR) underlies aging process and longevity. Previous work points to genetic and environmental factors associated with this risk.

OBJECTIVES

The aim of this research is to look for any CVR gene-gene and gene-multifactorial/lifestyle interactions that may impact health and disease and underlie exceptional longevity.

METHODS

A case-control study involving 521 both gender individuals, 253 centenarians (100.26 ± 1.98 years), and 268 controls (67.51 ± 3.25 years), low (LCR, = 107) and high (HCR, = 161) CVR. Hypertension, diabetes, obesity (BMI, kg·m), and impaired kidney function were defined according to standard criteria. CVR was calculated using Q risk®. DNA was genotyping (-rs4646994, -rs4762, -rs5182, -rs2960306, -rs1024323, 1799983, and -rs13306673) through iPlex-MassARRAY®, read by MALDI-TOF mass spectrometry, and analyzed by EARTDECODE®.

RESULTS

Antilongevity factors consisted (OR 95% CI, < 0.05) BMI 1.558 (1.445-1.680), hypertension 2.358 (1.565-3.553), smoking habits 4.528 (2.579-7.949), diabetes 5.553 (2.889-10.675), hypercholesterolemia 1.016 (1.010-1.022), and regular consumption of red meat 22.363 (13.987-35.755). Genetic aspects particularly for HCR individuals II (OR: 3.96 (1.83-8.56), < 0.0001) and TT (OR: 3.11 (1.70-5.70), < 0.0001) genotypes were also risk associate. Obesity, smoking, hypercholesterolemia, and frequent consumption of red meat have an additive action to hypertension in the longevity process. There was a synergistic interaction between the endothelial genotypes and the severity of arterial hypertension. An epistatic interaction between functional genetic variants of and angiotensinogen was also observed.

CONCLUSIONS

Cardiovascular risk-related genetic and multifactorial or predominantly lifestyle aspects and its interactions might influence the aging process and contribute to exceptional longevity in Portuguese centenarians. Besides lifestyle, the activity of nitrite oxide synthase may be one of the main physiologic regulators of cardiovascular protection in the path of longevity.

摘要

背景

心血管风险(CVR)是衰老过程和长寿的基础。先前的研究指出了与这种风险相关的遗传和环境因素。

目的

本研究旨在寻找可能影响健康和疾病并构成异常长寿基础的任何 CVR 基因-基因和基因-多因素/生活方式相互作用。

方法

这是一项涉及 521 名男女的病例对照研究,其中 253 名为百岁老人(100.26 ± 1.98 岁),268 名为对照(67.51 ± 3.25 岁),低(LCR,n = 107)和高(HCR,n = 161)CVR。根据标准标准定义高血压、糖尿病、肥胖症(BMI,kg·m)和肾功能受损。使用 Q 风险®计算 CVR。通过 iPlex-MassARRAY®进行 DNA 基因分型(-rs4646994、-rs4762、-rs5182、-rs2960306、-rs1024323、1799983 和 -rs13306673),通过 MALDI-TOF 质谱仪读取,并通过 EARTDECODE®进行分析。

结果

长寿的不利因素包括 BMI 1.558(1.445-1.680)、高血压 2.358(1.565-3.553)、吸烟习惯 4.528(2.579-7.949)、糖尿病 5.553(2.889-10.675)、高胆固醇血症 1.016(1.010-1.022)和经常食用红肉 22.363(13.987-35.755)。遗传方面,特别是对于 HCR 个体的 II(OR:3.96(1.83-8.56),<0.0001)和 TT(OR:3.11(1.70-5.70),<0.0001)基因型也与风险相关。肥胖、吸烟、高胆固醇血症和经常食用红肉在长寿过程中与高血压具有相加作用。内皮基因型与严重动脉高血压之间存在协同作用。还观察到血管紧张素原功能性遗传变异之间的上位性相互作用。

结论

与心血管风险相关的遗传和多因素或主要生活方式因素及其相互作用可能会影响衰老过程,并为葡萄牙百岁老人的长寿做出贡献。除了生活方式外,亚硝酸盐氧化酶的活性可能是心血管保护的主要生理调节剂之一。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2d4/7354649/162d4b4306d2/OMCL2020-1305413.001.jpg

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