Circulating Plasma Metabolites, Lifestyle Factors, and Mortality Risk

循环血浆代谢物、生活方式因素和死亡风险

• 批准号: 10461914
• 负责人: Marta Guasch-Ferre
• 金额: $ 19.94万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10461914
• 关键词: Adherence; Adult; Age; Aging; Amino Acids; Animal Model; Biological; Biology of Aging; Body mass index; Cardiovascular system; Clinical; Clinical Data; Cohort Studies; Data; Data Set; Diet; Follow-Up Studies; Fostering; Future; Genomics; Goals; Health; Health Professional; Health Promotion; Healthy Eating; Human; Individual; Intervention; Investigation; Knowledge; Life Expectancy; Life Style; Lipids; Longevity; Mediating; Metabolic; Metabolism; Molecular; National Institute on Aging; Nurses' Health Study; Oxidation-Reduction; Participant; Pathway Analysis; Pathway interactions; Personal Satisfaction; Plasma; Population; Prevention strategy; Process; Research; Resources; Risk; Sample Size; Spain; Supervision; Techniques; Women' s Health; Work; cardiovascular risk factor; cohort; design; effective intervention; follow-up; genetic risk factor; healthy aging; healthy lifestyle; improved; indexing; insight; interest; lifestyle data; lifestyle factors; lifestyle intervention; machine learning model; metabolomics; middle age; moderate-to-vigorous physical activity; mortality; mortality risk; multidisciplinary; never smoking; novel; potential biomarker; prospective; response; secondary analysis; small molecule; transcriptomics; Adherence; Adult; Age; Aging; Amino Acids; Animal Model; Biological; Biology of Aging; Body mass index; Cardiovascular system; Clinical; Clinical Data; Cohort Studies; Data; Data Set; Diet; Follow-Up Studies; Fostering; Future; Genomics; Goals; Health; Health Professional; Health Promotion; Healthy Eating; Human; Individual; Intervention; Investigation; Knowledge; Life Expectancy; Life Style; Lipids; Longevity; Mediating; Metabolic; Metabolism; Molecular; National Institute on Aging; Nurses' Health Study; Oxidation-Reduction; Participant; Pathway Analysis; Pathway interactions; Personal Satisfaction; Plasma; Population; Prevention strategy; Process; Research; Resources; Risk; Sample Size; Spain; Supervision; Techniques; Women' s Health; Work; cardiovascular risk factor; cohort; design; effective intervention; follow-up; genetic risk factor; healthy aging; healthy lifestyle; improved; indexing; insight; interest; lifestyle data; lifestyle factors; lifestyle intervention; machine learning model; metabolomics; middle age; moderate-to-vigorous physical activity; mortality; mortality risk; multidisciplinary; never smoking; novel; potential biomarker; prospective; response; secondary analysis; small molecule; transcriptomics

PROJECT SUMMARY/ABSTRACT Recent advances in high-throughput metabolomic studies have shown promise in elucidating potential pathways underpinning aging processes and longevity. However, data in human populations are still constrained by small sample sizes and a limited number of metabolites profiled. Existing studies have also not integrated data on diet and lifestyle to evaluate the associations of interest in a comprehensive manner. A better understanding of aging- related metabolic alterations and whether metabolite profiles are modulated by lifestyle factors is crucial to develop effective strategies to promote health and well-being. The main goal is to identify novel metabolite profiles associated with mortality and prolonged longevity, and investigate whether the metabolomic signatures of lifestyle factors are associated with mortality and longevity. We propose to leverage unique resources from two large U.S. cohorts with long follow-up and extended lifespan data: the Nurses’ Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS) (n~8,100). The results will be replicated in two independent populations: the Women’s Health Initiative (WHI) (n~2,300), and the Prevención con Dieta Mediterránea (PREDIMED) Study (n~3,000), a population at high cardiovascular risk in Spain. This research application is aimed at: (1) identifying plasma metabolomic profiles and networks associated with mortality and longevity; and, (2) identifying the metabolomic signatures of a healthy lifestyle score and examining its prospective association with mortality and longevity. The proposed project is built on the numerous strengths of existing cohort studies in U.S. and Mediterranean populations, and supporting results from the preliminary work conducted by our multi- disciplinary team. Findings from this study will provide insights into the underlying mechanisms of longevity and advance our understanding of how plasma metabolomics may mediate the associations between lifestyle factors and mortality risk. The proposed research will generate new knowledge that can directly inform specific lifestyle interventions applicable in clinical settings to improve the health and well-being of adults as they age. The proposed research will provide a wealth of preliminary data to stimulate further research on longevity and healthy aging.

项目摘要/摘要 高通量代谢组学研究的最新进展已显示出阐明潜在途径的希望 支撑老化过程和寿命。但是，人口中的数据仍然受到小的限制 样本量和有限数量的代谢产物进行了剖析。现有研究也没有整合饮食的数据 和生活方式，以全面的方式评估感兴趣的关联。更好地了解衰老 - 相关的代谢改变以及代谢产物轮廓是否受到生活方式因素的调节，对 制定有效的策略来促进健康和福祉。主要目标是识别新型代谢物 与死亡率和延长寿命相关的概况，并研究代谢组签名是否存在 生活方式因素与死亡率和寿命有关。我们建议利用独特的资源 两个大型美国队列，具有长时间的随访和延长的寿命数据：护士健康研究（NHS）和 卫生专业人员后续研究（HPFS）（N〜8,100）。结果将在两个独立 人群：妇女健康计划（WHI）（n〜2,300）和PrevenciónConDietaMediterránea （PREDIMED）研究（N〜3,000），西班牙高心血管风险的人群。该研究申请是 针对：（1）识别与死亡率和寿命相关的血浆代谢概况和网络；和， （2）确定健康生活方式评分的代谢组学特征并检查其潜在的关联 具有死亡率和寿命。拟议的项目建立在现有队列研究的众多优势基础上 在美国和地中海人口中 纪律团队。这项研究的结果将提供有关寿命和寿命基本机制的见解 促进我们对血浆代谢组学如何介导生活方式因素之间的关联的理解 和死亡风险。拟议的研究将产生可以直接告知特定生活方式的新知识 适用于临床环境的干预措施，以改善成年人的健康和福祉。 拟议的研究将提供大量的初步数据，以刺激对寿命和健康的进一步研究 老化。