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）中调查男性和女性代谢和心血管老化率的相关因素。 尽管可以在健康状况良好的情况下变老，但在美国人群中，渐进性体重增加（Yanovski et al 2000）和代谢综合征患病率增加是衰老的常见特征。 FLS中BMI > 25 kg/m2的成人患病率 从40岁的30%增加到60岁的70%，代谢综合征的患病率在同一年龄组的男性中从21%增加到38%，在女性中从14%增加到34%。 生长和发育的克里思速度：我们计划确定长期幼年状态的影响，即， 延缓生理发育的克里思，延缓代谢综合征、心血管疾病（CVD）和2型糖尿病（T2 DM）的发病。 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儿童生理发育的克里思联系起来。 将通过记录肥胖反弹时的年龄、青春期生长突增开始、身高峰值速度、月经初潮以及每个里程碑时的骨龄，确定每例受试者的生理发育克里思。这些里程碑的时间范围从肥胖反弹的5年到月经初潮的近8年不等，骨龄可能落后或超前实际年龄4.5年。 我们计划完成我们的目标，使用长期的连续数据收集的361名成年男性和354名成年女性在FLS从出生超过75年的时间。 青少年保护因素：我们还建议检查儿童和青少年时期测量的与代谢综合征、CVD和T2 DM延迟发作相关的生物标志物水平。 这种延迟可能是由于青少年时期的保护性因素持续到成年期，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少年时期测量的这些生物标志物中的哪一种可以延迟代谢综合征、CVD和T2 DM的发作，并且可以被认为是青少年保护因素。 对数十年来收集的系列数据的拟议分析应揭示代谢综合征、CVD和T2 DM发作的自然史与生命前20年期间生长和发育克里思的关系，以及与儿童和青春期生物标志物水平的关系，这些生物标志物可被视为青少年保护因素。我们正在研究儿童时期的特征，这些特征可以预防或延迟衰老的不健康方面的发生。

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.