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确定中国女性队列中的多模态衰老时钟。

Determining a multimodal aging clock in a cohort of Chinese women.

机构信息

CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China.

Center for Reproductive Medicine, Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, China; Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, China.

出版信息

Med. 2023 Nov 10;4(11):825-848.e13. doi: 10.1016/j.medj.2023.06.010. Epub 2023 Jul 28.

Abstract

BACKGROUND

Translating aging rejuvenation strategies into clinical practice has the potential to address the unmet needs of the global aging population. However, to successfully do so requires precise quantification of aging and its reversal in a way that encompasses the complexity and variation of aging.

METHODS

Here, in a cohort of 113 healthy women, tiled in age from young to old, we identified a repertoire of known and previously unknown markers associated with age based on multimodal measurements, including transcripts, proteins, metabolites, microbes, and clinical laboratory values, based on which an integrative aging clock and a suite of customized aging clocks were developed.

FINDINGS

A unified analysis of aging-associated traits defined four aging modalities with distinct biological functions (chronic inflammation, lipid metabolism, hormone regulation, and tissue fitness), and depicted waves of changes in distinct biological pathways peak around the third and fifth decades of life. We also demonstrated that the developed aging clocks could measure biological age and assess partial aging deceleration by hormone replacement therapy, a prevalent treatment designed to correct hormonal imbalances.

CONCLUSIONS

We established aging metrics that capture systemic physiological dysregulation, a valuable framework for monitoring the aging process and informing clinical development of aging rejuvenation strategies.

FUNDING

This work was supported by the National Natural Science Foundation of China (32121001), the National Key Research and Development Program of China (2022YFA1103700 and 2020YFA0804000), the National Natural Science Foundation of China (81502304), and the Quzhou Technology Projects (2022K46).

摘要

背景

将衰老干预策略转化为临床实践,有可能满足全球老龄化人口的未满足需求。然而,要成功实现这一目标,需要以一种涵盖衰老复杂性和变异性的方式,精确量化衰老及其逆转。

方法

在这里,在一个由 113 名健康女性组成的队列中,年龄从年轻到年老,我们根据多模态测量,包括转录本、蛋白质、代谢物、微生物和临床实验室值,确定了与年龄相关的已知和未知标志物谱,在此基础上开发了一个综合衰老时钟和一系列定制的衰老时钟。

发现

对与衰老相关特征的统一分析定义了具有不同生物学功能的四种衰老模式(慢性炎症、脂质代谢、激素调节和组织适应性),并描绘了不同生物学途径的变化波在生命的第三和第五个十年达到峰值。我们还证明,所开发的衰老时钟可以测量生物年龄,并通过激素替代疗法评估部分衰老减速,这是一种旨在纠正激素失衡的常见治疗方法。

结论

我们建立了衰老指标,这些指标可以捕捉系统性生理失调,为监测衰老过程和为衰老干预策略的临床开发提供了有价值的框架。

资助

本工作得到了国家自然科学基金(32121001)、国家重点研发计划(2022YFA1103700 和 2020YFA0804000)、国家自然科学基金(81502304)和衢州市科技项目(2022K46)的支持。

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