Exploring multi-omics and clinical characteristics linked to accelerated biological aging in Asian women of reproductive age: insights from the S-PRESTO study.

IF 10.4 1区 生物学 Q1 GENETICS & HEREDITY
Li Chen, Karen Mei-Ling Tan, Jia Xu, Priti Mishra, Sartaj Ahmad Mir, Min Gong, Kothandaraman Narasimhan, Bryan Ng, Jun Shi Lai, Mya Thway Tint, Shirong Cai, Suresh Anand Sadananthan, Navin Michael, Jadegoud Yaligar, Sambasivam Sendhil Velan, Melvin Khee Shing Leow, Kok Hian Tan, Jerry Chan, Michael J Meaney, Shiao-Yng Chan, Yap Seng Chong, Johan G Eriksson
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引用次数: 0

Abstract

Background: Phenotypic age (PhenoAge), a widely used marker of biological aging, has been shown to be a robust predictor of all-cause mortality and morbidity in different populations. Existing studies on biological aging have primarily focused on individual domains, resulting in a lack of a comprehensive understanding of the multi-systemic dysregulation that occurs in aging.

Methods: PhenoAge was evaluated based on a linear combination of chronological age (CA) and 9 clinical biomarkers in 952 multi-ethnic Asian women of reproductive age. Phenotypic age acceleration (PhenoAgeAccel), an aging biomarker, represents PhenoAge after adjusting for CA. This study conducts an in-depth association analysis of PhenoAgeAccel with clinical, nutritional, lipidomic, gut microbiome, and genetic factors.

Results: Higher adiposity, glycaemia, plasma saturated fatty acids, kynurenine pathway metabolites, GlycA, riboflavin, nicotinamide, and insulin-like growth factor binding proteins were positively associated with PhenoAgeAccel. Conversely, a healthier diet and higher levels of pyridoxal phosphate, all-trans retinol, betaine, tryptophan, glutamine, histidine, apolipoprotein B, and insulin-like growth factors were inversely associated with PhenoAgeAccel. Lipidomic analysis found 132 lipid species linked to PhenoAgeAccel, with PC(O-36:0) showing the strongest positive association and CE(24:5) demonstrating the strongest inverse association. A genome-wide association study identified rs9864994 as the top genetic variant (P = 5.69E-07) from the ZDHHC19 gene. Gut microbiome analysis revealed that Erysipelotrichaceae UCG-003 and Bacteroides vulgatus were inversely associated with PhenoAgeAccel. Integrative network analysis of aging-related factors underscored the intricate links among clinical, nutritional and lipidomic variables, such as positive associations between kynurenine pathway metabolites, amino acids, adiposity, and insulin resistance. Furthermore, potential mediation effects of blood biomarkers related to inflammation, immune response, and nutritional and energy metabolism were observed in the associations of diet, adiposity, genetic variants, and gut microbial species with PhenoAgeAccel.

Conclusions: Our findings provide a comprehensive analysis of aging-related factors across multiple platforms, delineating their complex interconnections. This study is the first to report novel signatures in lipidomics, gut microbiome and blood biomarkers specifically associated with PhenoAgeAccel. These insights are invaluable in understanding the molecular and metabolic mechanisms underlying biological aging and shed light on potential interventions to mitigate accelerated biological aging by targeting modifiable factors.

探索与亚洲育龄妇女生物老化加速有关的多组学和临床特征:S-PRESTO 研究的启示。
背景:表型年龄(PhenoAge)是一种广泛使用的生物老化标志物,已被证明是不同人群全因死亡率和发病率的可靠预测指标。现有的生物衰老研究主要集中在单个领域,导致对衰老过程中出现的多系统失调缺乏全面了解:方法:对 952 名多种族亚洲育龄妇女的表型年龄(PhenoAge)进行了评估,该评估基于计时年龄(CA)和 9 种临床生物标志物的线性组合。表型年龄加速度(PhenoAgeAccel)是一种衰老生物标志物,代表了调整 CA 后的 PhenoAge。本研究对 PhenoAgeAccel 与临床、营养、脂质组、肠道微生物组和遗传因素进行了深入的关联分析:结果:较高的脂肪率、糖血症、血浆饱和脂肪酸、犬尿氨酸途径代谢物、GlycA、核黄素、烟酰胺和胰岛素样生长因子结合蛋白与 PhenoAgeAccel 呈正相关。相反,更健康的饮食和更高水平的磷酸吡哆醛、全反式视黄醇、甜菜碱、色氨酸、谷氨酰胺、组氨酸、脂蛋白 B 和胰岛素样生长因子与 PhenoAgeAccel 呈反比。脂质体分析发现,132 种脂质与 PhenoAgeAccel 有关,其中 PC(O-36:0) 的正相关性最强,CE(24:5) 的反相关性最强。一项全基因组关联研究发现,rs9864994 是 ZDHHC19 基因的最大遗传变异(P = 5.69E-07)。肠道微生物组分析表明,Erysipelotrichaceae UCG-003 和 Bacteroides vulgatus 与 PhenoAgeAccel 呈反相关。对衰老相关因素的整合网络分析强调了临床、营养和脂质体变量之间错综复杂的联系,例如犬尿氨酸途径代谢物、氨基酸、脂肪和胰岛素抵抗之间的正相关。此外,在饮食、脂肪、遗传变异和肠道微生物物种与 PhenoAgeAccel 的关联中,还观察到了与炎症、免疫反应、营养和能量代谢有关的血液生物标志物的潜在中介效应:我们的研究结果通过多个平台对衰老相关因素进行了全面分析,并勾勒出它们之间复杂的相互联系。本研究首次报告了与 PhenoAgeAccel 特别相关的脂质组学、肠道微生物组和血液生物标志物的新特征。这些见解对于了解生物衰老的分子和代谢机制非常有价值,并揭示了通过针对可改变的因素来缓解生物加速衰老的潜在干预措施。
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来源期刊
Genome Medicine
Genome Medicine GENETICS & HEREDITY-
CiteScore
20.80
自引率
0.80%
发文量
128
审稿时长
6-12 weeks
期刊介绍: Genome Medicine is an open access journal that publishes outstanding research applying genetics, genomics, and multi-omics to understand, diagnose, and treat disease. Bridging basic science and clinical research, it covers areas such as cancer genomics, immuno-oncology, immunogenomics, infectious disease, microbiome, neurogenomics, systems medicine, clinical genomics, gene therapies, precision medicine, and clinical trials. The journal publishes original research, methods, software, and reviews to serve authors and promote broad interest and importance in the field.
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