Kuo Chia-Ling, Liu Peiran, Drouard Gabin, Vuoksimaa Eero, Kaprio Jaakko, Ollikainen Miina, Chen Zhiduo, Pilling Luke C, Atkins Janice L, Fortinsky Richard H, Kuchel George A, Diniz Breno S
Department of Public Health Sciences, University of Connecticut Health Center, Farmington Connecticut, USA.
The Cato T. Laurencin Institute for Regenerative Engineering, University of Connecticut Health Center, Farmington, Connecticut, USA.
medRxiv. 2025 Mar 28:2024.06.26.24309530. doi: 10.1101/2024.06.26.24309530.
The focus of aging research has shifted from increasing lifespan to enhancing healthspan to reduce the time spent living with disability. Despite significant efforts to develop biomarkers of aging, few studies have focused on biomarkers of healthspan. We developed a proteomics-based signature of healthspan (healthspan proteomic score (HPS)) using proteomic data from the Olink Explore 3072 assay in the UK Biobank Pharma Proteomics Project (53,018 individuals and 2920 proteins). A lower HPS was associated with higher mortality risk and several age-related conditions, such as COPD, diabetes, heart failure, cancer, myocardial infarction, dementia, and stroke. HPS showed superior predictive accuracy for these outcomes compared to other biological age measures. Proteins associated with HPS were enriched in hallmark pathways such as immune response, inflammation, cellular signaling, and metabolic regulation. The external validity was evaluated using the Essential Hypertension Epigenetics study with proteomic data also from the Olink Explore 3072 and complementary epigenetic data, making it a valuable tool for assessing healthspan and as a potential surrogate marker to complement existing proteomic and epigenetic biological age measures in geroscience-guided studies.
衰老研究的重点已从延长寿命转向提高健康寿命，以减少与残疾相伴的时间。尽管在开发衰老生物标志物方面付出了巨大努力，但很少有研究关注健康寿命的生物标志物。我们利用英国生物银行药物蛋白质组学项目中Olink Explore 3072检测的蛋白质组数据（53018名个体和2920种蛋白质），开发了一种基于蛋白质组学的健康寿命特征（健康寿命蛋白质组评分（HPS））。较低的HPS与较高的死亡风险以及几种与年龄相关的疾病相关，如慢性阻塞性肺疾病、糖尿病、心力衰竭、癌症、心肌梗死、痴呆和中风。与其他生物学年龄指标相比，HPS对这些结果显示出更高的预测准确性。与HPS相关的蛋白质在免疫反应、炎症、细胞信号传导和代谢调节等标志性通路中富集。使用原发性高血压表观遗传学研究评估了外部有效性，该研究也使用了来自Olink Explore 3072的蛋白质组数据和补充的表观遗传学数据，使其成为评估健康寿命的有价值工具，并且作为一种潜在的替代标志物，可在老年科学指导的研究中补充现有的蛋白质组学和表观遗传学生物学年龄指标。
