Juvenile Protective Factors and Their Effects on Aging

青少年保护因素及其对衰老的影响

• 批准号: 9026730
• 负责人: SHUMEI S SUN
• 金额: $ 38.02万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-15 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9026730
• 关键词: Address; Adolescence; Adolescent; Adult; Affect; Age; Aging; Binding Proteins; Birth; Blood Circulation; Cardiovascular Diseases; Caring; Child; Childhood; Clinical assessments; Data Set; Databases; Diastolic blood pressure; Disease; Dyslipidemias; Fasting; Fatty acid glycerol esters; Female; Future; Goals; Health; High Density Lipoprotein Cholesterol; High Density Lipoproteins; Hypertension; Impaired fasting glycaemia; Incidence; Individual; Insulin-Like Growth Factor I; Insulin-Like Growth-Factor Binding Protein 1; Intervention; Lead; Life Style; Literature; Logistics; Longevity; Longitudinal Studies; Malignant Neoplasms; Measurement; Mediating; Mediation; Medical; Metabolic syndrome; Modeling; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Osteocalcin; Osteoporosis; Participant; Plasma; Prevalence; Prevention; Preventive; Public Health; Research; Risk; Risk Factors; Sampling; Source; Therapeutic; Time; adiponectin; age related; base; cationic antimicrobial protein CAP 37; cost; delay sexual debut; early onset; healthy aging; human capital; human very old age (85+); insulin sensitivity; male; novel; novel therapeutics; osteoporosis with pathological fracture; public health relevance; sex; sexual dimorphism

 DESCRIPTION (provided by applicant): We plan to analyze the data set generated by 2567 participants in the Fels Longitudinal Study over a period of eight decades in order to ascertain if certain putative juvenile protective factors and juvenile protective states can delay the onset of age related disease (ARD) and increase longevity in subjects who retain juvenile levels of such protective factors and states in adulthood. Although it is possible to age in good health, obesity, hypertension (HBP), dyslipidemia, and impaired fasting glucose are frequent concomitants of aging, as well as type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), cancer, and osteoporosis (OP). These conditions all increase in prevalence with age, and age is the primary risk factor for cancer, CVD, and osteoporotic fractures. The putative JPF we plan to study are adiponectin, osteocalcin, and insulin-like growth factor-1 binding protein 3 (IGF1BP3). There is evidence in the literature that these putative JPF are associated with either enhanced survival and/or a delay in the onset of ARD. A defining attribute of a JPF is that it could theoretically be replenished from exogenous sources to re-establish juvenile levels in the circulation in order to engender a delay in the onset of ARD or even to reverse established ARD. Unlike JPF, JPS could not be added to the circulation from exogenous sources. However, significant changes in JPS can be attained by life-style and/or pharmacologic means. Therefore, we will examine the effects of persistence of juvenile levels of these protective states in FLS adult participants on te onset of ARD. The putative JPS we plan to study include high fat-free mass/ht2 (FFM/ht2), high insulin sensitivity high HDL- cholesterol, and low systolic and/or diastolic blood pressure (SBP/DBP. Should we confirm that some or all of these JPF and JPS are associated with a delayed onset of ARD and/or with an extended life span, our findings may be applied in clinical assessments of individuals whose JPF and JPS trajectories diverge from those that predict delayed onset of ARD. It may also be possible to develop novel therapies based on maintaining or restoring juvenile levels of these protective factors and states in adulthood to delay the onset of ARD or reverse established ARD. We recognize that major logistic and regulatory hurdles must be cleared before such novel preventive or therapeutic approaches can be applied.

 描述（由申请人提供）：我们计划分析 2567 名 Fels 纵向研究参与者在 80 年间生成的数据集，以确定是否 某些假定的青少年保护因素和青少年保护状态可以延迟年龄相关疾病（ARD）的发作，并延长成年后保留青少年水平的此类保护因素和状态的受试者的寿命。虽然身体健康有可能变老，但肥胖， 高血压 (HBP)、血脂异常和空腹血糖受损是衰老的常见伴随因素，此外还有 2 型糖尿病 (T2DM)、心血管疾病 (CVD)、癌症和骨质疏松症 (OP)。这些疾病的患病率都随着年龄的增长而增加，而年龄是癌症、心血管疾病和骨质疏松性骨折的主要危险因素。我们计划研究的假定 JPF 是脂联素、骨钙素和胰岛素样生长因子 1 结合蛋白 3 (IGF1BP3)。文献中有证据表明，这些假定的 JPF 与提高生存率和/或延迟 ARD 发病有关。 JPF 的一个定义属性是，理论上它可以是 从外源补充，以重建循环中的幼体水平，从而延迟 ARD 的发作，甚至逆转已建立的 ARD。与 JPF 不同，JPS 无法从外源添加到流通中。然而，JPS 的显着改变可以通过生活方式和/或药物手段实现。因此，我们将研究 FLS 成年参与者中这些保护状态的青少年水平的持续性对 ARD 发作的影响。我们计划研究的假定 JPS 包括高无脂体重/ht2 (FFM/ht2)、高胰岛素敏感性、高 HDL- 胆固醇和低收缩压和/或舒张压 (SBP/DBP)。如果我们确认这些 JPF 和 JPS 中的部分或全部与 ARD 延迟发作和/或延长寿命有关，我们的研究结果可能会应用于个人的临床评估 其 JPF 和 JPS 轨迹与预测 ARD 延迟发作的轨迹不同。也有可能开发出基于维持或恢复这些保护因素的青少年水平和成年状态的新疗法，以延缓发病 ARD 或反向建立的 ARD。我们认识到，在应用这种新颖的预防或治疗方法之前，必须清除主要的后勤和监管障碍。