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迈向健康长寿:从分子靶点和生物标志物到生物钟的综合见解。

Towards Healthy Longevity: Comprehensive Insights from Molecular Targets and Biomarkers to Biological Clocks.

机构信息

Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore.

Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.

出版信息

Int J Mol Sci. 2024 Jun 20;25(12):6793. doi: 10.3390/ijms25126793.

Abstract

Aging is a complex and time-dependent decline in physiological function that affects most organisms, leading to increased risk of age-related diseases. Investigating the molecular underpinnings of aging is crucial to identify geroprotectors, precisely quantify biological age, and propose healthy longevity approaches. This review explores pathways that are currently being investigated as intervention targets and aging biomarkers spanning molecular, cellular, and systemic dimensions. Interventions that target these hallmarks may ameliorate the aging process, with some progressing to clinical trials. Biomarkers of these hallmarks are used to estimate biological aging and risk of aging-associated disease. Utilizing aging biomarkers, biological aging clocks can be constructed that predict a state of abnormal aging, age-related diseases, and increased mortality. Biological age estimation can therefore provide the basis for a fine-grained risk stratification by predicting all-cause mortality well ahead of the onset of specific diseases, thus offering a window for intervention. Yet, despite technological advancements, challenges persist due to individual variability and the dynamic nature of these biomarkers. Addressing this requires longitudinal studies for robust biomarker identification. Overall, utilizing the hallmarks of aging to discover new drug targets and develop new biomarkers opens new frontiers in medicine. Prospects involve multi-omics integration, machine learning, and personalized approaches for targeted interventions, promising a healthier aging population.

摘要

衰老是一种复杂的、随时间而衰退的生理功能,影响着大多数生物体,导致与年龄相关的疾病风险增加。研究衰老的分子基础对于确定抗衰老物质、准确量化生物年龄以及提出健康长寿方法至关重要。

本综述探讨了目前作为干预靶点和衰老生物标志物研究的分子、细胞和系统层面的途径。针对这些标志的干预措施可能会改善衰老过程,其中一些已进入临床试验。这些标志的生物标志物用于估计生物年龄和与衰老相关疾病的风险。利用衰老生物标志物,可以构建预测异常衰老、与衰老相关疾病和死亡率增加的生物年龄时钟。因此,生物年龄估计可以通过提前预测全因死亡率来提供精细的风险分层基础,从而为干预提供机会。

然而,尽管技术有所进步,但由于个体差异和这些生物标志物的动态性质,仍然存在挑战。为了解决这些问题,需要进行纵向研究以稳健地识别生物标志物。

总之,利用衰老的标志来发现新的药物靶点和开发新的生物标志物为医学开辟了新的前沿。前景包括多组学整合、机器学习和针对目标干预的个性化方法,有望使人口更加健康地衰老。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afc2/11203944/780ceb127655/ijms-25-06793-g001.jpg

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