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代谢和心血管衰老率相关的因素。虽然在健康状态下衰老是可能的，但在美国人口中，体重的逐渐增加（Yanovski et al . 2000）和代谢综合征的日益流行是衰老的共同特征。BMI为0 ~ 25kg/m2的FLS成人患病率从第4个10岁的30%增加到第6个10岁的70%，同一年龄组男性代谢综合征患病率从21%增加到38%，女性从14%增加到34%。生长和发育的节奏：我们计划确定延长的青少年状态，即生理发育的迟缓节奏，对延迟代谢综合征、心血管疾病（CVD）和2型糖尿病（T2DM）发病的影响。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儿童时期的生理发育速度联系起来。每个受试者的生理发育速度将通过记录其肥胖反弹时的年龄来确定；青春期：青春期生长突增的开始；峰高速度；月经初潮;以及他或她在每个里程碑的骨骼年龄。这些里程碑的时间范围各不相同，从肥胖反弹的5年到月经初潮的近8年，骨龄可能在任何方向上都比实足年龄滞后或提前4.5年。我们计划利用从FLS的361名成年男性和354名成年女性长达75年的出生中收集的长期序列数据来实现我们的目标。青少年保护因素：我们还建议检查儿童和青少年时期测量的与代谢综合征、CVD和T2DM延迟发病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因素持续到成年，或者是由于这些因素在童年时期所产生的影响持续到成年。我们将研究的生物标志物包括身体成分、脂质谱、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，哪些可以延迟代谢综合征、CVD和T2DM的发病，并被认为是青少年保护因素。对几十年来收集的系列数据的分析应该揭示代谢综合征、CVD和T2DM发病的自然历史与生命最初20年的生长发育速度以及与儿童和青少年时期可被认为是青少年保护因素的生物标志物水平的关系。我们正在研究儿童的特征，以防止或延缓衰老的不健康方面的发作。

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.