Prolonged Juvenile State and Juvenile Protective Factors Affect Chronic Diseases

描述(由申请人提供)：我们将在FELS纵向研究(FLS)中调查与男性和女性的代谢和心血管衰老速度有关的因素。虽然健康地变老是可能的，但在美国人口中，逐渐增加的体重(Yanovski等人，2000年)和日益普遍的代谢综合征是衰老的共同特征。在FLS中，BMI和GT；25 kg/m2的成年人的患病率从生命的第四个十年的30%上升到第六个十年的70%，代谢综合征的患病率在男性从21%增加到38%，在相同年龄组的女性从14%增加到34%。生长发育速度：我们计划确定长期的青少年状态，即生理发育速度减慢，对于延缓代谢综合征、心血管疾病(CVD)和2型糖尿病(T2 DM)的发病有何影响。为了实现这一目标，我们建议将这些常见但不健康的衰老特征的风险因素与童年生理发展的节奏联系起来。每个受试者的生理发育速度将通过记录他或她在肥胖反弹时的年龄、青春期生长激增的开始时间、身高峰值速度、月经初潮以及他或她在每个里程碑时的骨龄来确定。这些里程碑的时间范围从肥胖症反弹的5年到月经初潮的近8年不等，骨龄可能在两个方向上落后或超前实际年龄长达4.5年。我们计划使用FLS中361名成年男性和354名成年女性从出生开始收集的长达75年的长期系列数据来实现我们的目标。青少年保护因素：我们还建议检查在儿童和青春期测量的生物标志物水平，这些生物标志物与代谢综合征、心血管疾病和T2 DM的延迟发病有关。造成这种延迟的原因可能是青少年将保护性因素的水平持续到成年，或者是由于这些因素在童年时期引发的影响持续到成年期。我们将研究的生物标志物包括身体成分、血脂谱、脂肪因子、炎症标志物、胰岛素抵抗、胰岛素样生长因子-1(IGF-1)和肾上腺雄激素。我们计划确定在儿童和青春期测量的这些生物标记物中的哪些可以延缓代谢综合征、心血管疾病和T2 DM的发生，并可被视为青少年保护因素。拟议的对几十年来收集的系列数据的分析应该揭示代谢综合征、心血管疾病和T2 DM发病的自然历史，与生命头20年的生长和发展节奏以及儿童和青少年时期可被视为青少年保护因素的生物标记物水平有关。我们正在研究儿童时期的特征，这些特征可以预防或延缓衰老的不健康方面的出现。

DESCRIPTION (provided by applicant): We will investigate factors involved in the rate of metabolic and cardiovascular aging in men and women in the Fels Longitudinal Study (FLS). Although it is possible to age in good health, in the U.S. population progressive weight gain (Yanovski et al 2000) and an increasing prevalence of the metabolic syndrome are common attributes of aging. The prevalence of adults in the FLS with BMI > 25kg/m2 increases from 30% in the fourth decade of life to 70% in the sixth decade, and the prevalence of the metabolic syndrome increase from 21% to 38% in men and from 14% to 34% in women the same age groups. Tempo of growth and development: We plan to ascertain the influence of a prolonged juvenile state, i.e., a retarded tempo of physiological development, on delaying the onset of the metabolic syndrome, cardiovascular disease (CVD), and type 2 diabetes mellitus (T2DM) later in life. To achieve this goal, we propose to link risk factors for these common but unhealthy features of aging to childhood tempo of physiological development. The tempo of physiological development will be determined in each subject by documenting his or her age at the time of the adiposity rebound; the onset of the pubertal growth spurt; the peak height velocity; menarche; and his or her bone age at each of these milestones. The temporal range of these milestones varies from 5 years for the adiposity rebound to nearly 8 years for menarche, and bone age may lag behind or jump ahead of chronological age by as much as 4.5 years in either direction. We plan to accomplish our objectives using long-term serial data collected from birth over periods as long as 75 years in 361 adult males and 354 adult females in the FLS. Juvenile protective factors: We also propose to examine levels of biomarkers measured in childhood and adolescence that are associated with a delayed onset of the metabolic syndrome, CVD, and T2DM. Such delays may be caused by the persistence of juvenile levels of protective factors into adulthood, or else by the persistence into adulthood of effects initiated by such factors in childhood. The biomarkers we will study include body composition, lipid profiles, adipokines, inflammatory markers, insulin resistance, insulin-like growth factor-1 (IGF-1), and adrenal androgens. We plan to identify which of these biomarkers measured during childhood and adolescence act to delay the onset of the metabolic syndrome, CVD, and T2DM and could be considered as juvenile protective factors. The proposed analysis of serial data collected over decades should reveal the natural history of the onset of the metabolic syndrome, CVD, and T2DM in relation to the tempo of growth and development during the first two decades of life and in relation to levels of biomarkers during childhood and adolescence that could be considered to be juvenile protective factors. We are examining features of childhood that prevent or delay the onset of unhealthy aspects of aging.