Juvenile Protective Factors and Their Effects on Aging

 描述（由申请人提供）：我们计划分析Fels纵向研究中2567名参与者在80年内产生的数据集，以确定 某些推定的青少年保护因子和青少年保护状态可以延迟年龄相关疾病（ARD）的发作，并增加在成年时保持青少年水平的这种保护因子和状态的受试者的寿命。虽然有可能在健康的年龄，肥胖， 高血压（HBP）、血脂异常和空腹血糖受损是衰老以及2型糖尿病（T2 DM）、心血管疾病（CVD）、癌症和骨质疏松症（OP）的常见伴随物。这些疾病的患病率都随着年龄的增长而增加，年龄是癌症，CVD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（IGF 1BP 3）。文献中有证据表明，这些假定的JPF与生存率提高和/或ARD发作延迟相关。JPF的一个定义属性是，理论上它可以 从外源性来源补充，以重新建立循环中的幼年水平，从而延迟ARD的发作或甚至逆转已建立的ARD。与JPF不同，JPS不能从外源来源加入到流通中。然而，JPS的显著变化可以通过生活方式和/或药理学手段来实现。因此，我们将研究FLS成人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包括高去脂质量/ht 2（FFM/ht 2）、高胰岛素敏感性、高HDL-胆固醇和低收缩压和/或舒张压（SBP/DBP）。如果我们证实这些JPF和JPS中的一些或全部与ARD延迟发作和/或延长寿命相关，则我们的研究结果可应用于JPF和JPS轨迹偏离ARD延迟发作预测的个体的临床评估。也有可能开发基于维持或恢复这些保护因子的青少年水平和成年状态的新疗法，以延迟发病。 或反向建立ARD。我们认识到，在应用这种新的预防或治疗方法之前，必须清除主要的后勤和监管障碍。

 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.