Epigenetic Age Measures to Predict COVID-19 Symptom Progression and Severity

表观遗传年龄测量可预测 COVID-19 症状进展和严重程度

• 批准号: 10158592
• 负责人: Morgan Elyse Levine
• 金额: $ 13.94万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-01 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10158592
• 关键词: Admission activity; Adult; Age; Aging; Alleles; Biological; Biological Aging; Biological Markers; COVID-19; COVID-19 pandemic; Cardiovascular Diseases; Cells; Centers for Disease Control and Prevention (U.S.); Cessation of life; Chronic Disease; Chronic Kidney Failure; Chronic Obstructive Airway Disease; Chronology; Clinic; Clinical; Communities; DNA Methylation; Data; Development; Diabetes Mellitus; Disease; Ensure; Epigenetic Process; Etiology; Future; General Population; Genome; Geroscience; Grant; Health; Heart Diseases; High Prevalence; Home environment; Hybrids; Hypertension; Immunocompetence; Incidence; Individual; Individual Differences; Infection; Lifting; Liver diseases; Lung diseases; Machine Learning; Measurement; Measures; Medical; Methods; Methylation; Molecular; Morbidity - disease rate; Nature; Organism; Pathogenicity; Patients; Pattern; Persons; Physiological; Population; Population Research; Predisposition; Process; Proxy; Risk; Risk Factors; Risk stratification; Running; Sampling; Sensitivity and Specificity; Severities; Site; Speed; Support System; Symptoms; Techniques; Technology; Testing; Time; Tissues; Triage; United States; Ventilator; Virus; Virus Diseases; Work; age related; base; bisulfite; cell type; clinical application; clinical risk; coronavirus disease; cost; cost effective; genome-wide; human very old age (85+); molecular marker; mortality; mortality risk; multidisciplinary; novel; older patient; predictive marker; preservation; resilience; response; social; transmission process; trend

PROJECT SUMMARY The risk of fatality and/or severe complications due to COVID-19 infection is strongly age dependent. Data from the CDC suggests that those ages 85 and older have predicted mortality rates that is 100-fold higher than for those under the age of 50 and currently, 8 out of 10 COVID-19 deaths in the United States were in adults age 65 or older. While the exact etiology underlying this age disparity is unknown, evidence suggests that vulnerability may be due to changes that occur as a function of the aging process. This is further evidenced by the pattern of increased vulnerability among persons with pre-existing diseases of aging—cardiovascular disease, diabetes, COPD, chronic kidney disease, liver disease—suggesting that it isn't just chronological age that determines risk, but rather, biological age. In recent years, our group has helped develop some of the most robust biomarkers available, namely the epigenetic clocks. These measures estimate biological age in a sample based on DNA methylation levels at hundreds to thousands of CpG sites across the genome. Not only do epigenetic clocks track with age in diverse tissues and cell types, but discrepancies between epigenetic age and actual age have also been shown to predict risk of mortality and incidence of major chronic disease, including those which appear to be major risk factors for COVID-19. However, in order for these measures to be informative for assessing COVID-19 risk clinically, or in the general population, 1) they need to be re-optimized to capture the aspects of biological aging specific to COVID-19 susceptibility, and 2) advances in technology need to be made to ensure lower costs and rapid turnaround. This proposal aims to build on our team's multidisciplinary strengths to develop and validate a targeted, lab-developed, readily-available test to predict COVID-19 symptomology and mortality risk. If successful, this test will have widespread applications—from informing triage and treatment decisions in the clinic, to guiding social and pollical decisions when it comes to lifting “stay-at-home” orders for certain individuals.

项目摘要 COVID-19感染导致死亡和/或严重并发症的风险与年龄密切相关。 依赖。来自疾病预防控制中心的数据表明，那些年龄在85岁及以上的人预测了死亡率， 这是50岁以下人群的100倍，目前，10个COVID-19死亡病例中有8个 在美国是65岁或以上的成年人。虽然这个年龄的确切病因 差异是未知的，有证据表明，脆弱性可能是由于发生的变化， 老化过程的功能。脆弱性增加的模式进一步证明了这一点 在原有老年疾病-心血管疾病、糖尿病、COPD、 慢性肾脏疾病，肝脏疾病-这表明它不仅仅是实际年龄决定了 风险，而是生物年龄。 近年来，我们的团队帮助开发了一些最可靠的生物标志物， 即表观遗传时钟。这些措施估计生物年龄在一个样本的基础上DNA 在整个基因组中数百至数千个CpG位点的甲基化水平。表观遗传学不仅 在不同的组织和细胞类型中，生物钟会随着年龄的增长而变化，但表观遗传年龄和 实际年龄也被证明可以预测死亡风险和主要慢性病的发病率， 包括那些似乎是COVID-19的主要风险因素。然而，为了使这些 为临床或一般人群评估COVID-19风险提供信息的措施，1） 它们需要重新优化，以捕捉COVID-19特有的生物衰老方面 敏感性，以及2）需要技术进步，以确保降低成本和快速 转机 该提案旨在利用我们团队的多学科优势，开发和验证 有针对性的，实验室开发的，现成的测试，以预测COVID-19的发病率和死亡率风险。 如果成功的话，这种测试将有广泛的应用-从通知分流和治疗 在诊所的决定，指导社会和政治决策时，解除“呆在家里” 对某些人的命令。

项目成果

Vasomotor symptoms and accelerated epigenetic aging in the Women's Health Initiative (WHI).

• DOI: 10.1210/clinem/dgaa081
• 发表时间: 2020-02
• 期刊: The Journal of clinical endocrinology and metabolism
• 作者: R. Thurston;J. Carroll;M. Levine;Yuefang Chang;C. Crandall;J. Manson;L. Pal;L. Hou;A. Shadyab-A.-Shad

Genetic associations for two biological age measures point to distinct aging phenotypes.

• DOI: 10.1111/acel.13376
• 发表时间: 2021-06
• 期刊: Aging cell
• 影响因子: 7.8
• 作者: Kuo CL;Pilling LC;Liu Z;Atkins JL;Levine ME
• 通讯作者: Levine ME

Biological Aging Predicts Vulnerability to COVID-19 Severity in UK Biobank Participants.

• DOI: 10.1093/gerona/glab060
• 发表时间: 2021-07-13
• 期刊: The journals of gerontology. Series A, Biological sciences and medical sciences
• 作者: Kuo CL;Pilling LC;Atkins JL;Masoli JAH;Delgado J;Tignanelli C;Kuchel GA;Melzer D;Beckman KB;Levine ME
• 通讯作者: Levine ME

A rat epigenetic clock recapitulates phenotypic aging and co-localizes with heterochromatin.

• DOI: 10.7554/elife.59201
• 发表时间: 2020-11-12
• 期刊: eLife
• 影响因子: 7.7
• 作者: Levine M;McDevitt RA;Meer M;Perdue K;Di Francesco A;Meade T;Farrell C;Thrush K;Wang M;Dunn C;Pellegrini M;de Cabo R;Ferrucci L
• 通讯作者: Ferrucci L

A new aging measure captures morbidity and mortality risk across diverse subpopulations from NHANES IV: A cohort study.

• DOI: 10.1371/journal.pmed.1002718
• 发表时间: 2018-12-01
• 期刊: PLoS medicine
• 影响因子: 15.8
• 作者: Liu, Zuyun;Kuo, Pei-Lun;Levine, Morgan
• 通讯作者: Levine, Morgan