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与无重大慢性疾病相关的衰老生物标志物特征:基于人群的 EPIC-Potsdam 队列研究结果。

Biomarker signatures associated with ageing free of major chronic diseases: results from a population-based sample of the EPIC-Potsdam cohort.

机构信息

Department of Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany.

Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.

出版信息

Age Ageing. 2024 May 11;53(Suppl 2):ii60-ii69. doi: 10.1093/ageing/afae041.

Abstract

BACKGROUND

A number of biomarkers denoting various pathophysiological pathways have been implicated in the aetiology and risk of age-related diseases. Hence, the combined impact of multiple biomarkers in relation to ageing free of major chronic diseases, such as cancer, cardiovascular disease and type 2 diabetes, has not been sufficiently explored.

METHODS

We measured concentrations of 13 biomarkers in a random subcohort of 2,500 participants in the European Prospective Investigation into Cancer and Nutrition Potsdam study. Chronic disease-free ageing was defined as reaching the age of 70 years within study follow-up without major chronic diseases, including cardiovascular disease, type 2 diabetes or cancer. Using a novel machine-learning technique, we aimed to identify biomarker clusters and explore their association with chronic disease-free ageing in multivariable-adjusted logistic regression analysis taking socio-demographic, lifestyle and anthropometric factors into account.

RESULTS

Of the participants who reached the age of 70 years, 321 met our criteria for chronic-disease free ageing. Machine learning analysis identified three distinct biomarker clusters, among which a signature characterised by high concentrations of high-density lipoprotein cholesterol, adiponectin and insulin-like growth factor-binding protein 2 and low concentrations of triglycerides was associated with highest odds for ageing free of major chronic diseases. After multivariable adjustment, the association was attenuated by socio-demographic, lifestyle and adiposity indicators, pointing to the relative importance of these factors as determinants of healthy ageing.

CONCLUSION

These data underline the importance of exploring combinations of biomarkers rather than single molecules in understanding complex biological pathways underpinning healthy ageing.

摘要

背景

许多生物标志物表示各种病理生理途径,与年龄相关疾病的病因和风险有关。因此,尚未充分探讨与无重大慢性疾病(如癌症、心血管疾病和 2 型糖尿病)相关的衰老有关的多种生物标志物的综合影响。

方法

我们在欧洲癌症前瞻性调查和营养波茨坦研究的 2500 名随机亚组参与者中测量了 13 种生物标志物的浓度。无重大慢性疾病的衰老定义为在研究随访中达到 70 岁而无重大慢性疾病,包括心血管疾病、2 型糖尿病或癌症。使用一种新的机器学习技术,我们旨在确定生物标志物簇,并在多变量调整的逻辑回归分析中探索它们与无重大慢性疾病的衰老之间的关联,同时考虑社会人口统计学、生活方式和人体测量因素。

结果

在达到 70 岁的参与者中,有 321 人符合我们无慢性疾病衰老的标准。机器学习分析确定了三个不同的生物标志物簇,其中一个特征是高密度脂蛋白胆固醇、脂联素和胰岛素样生长因子结合蛋白 2浓度高,甘油三酯浓度低,与无重大慢性疾病衰老的几率最高。在多变量调整后,社会人口统计学、生活方式和肥胖指标减弱了这种关联,表明这些因素作为健康衰老决定因素的相对重要性。

结论

这些数据强调了探索生物标志物组合而不是单个分子在理解健康衰老背后复杂生物学途径的重要性。

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