Determinants of Leukocyte Telomere Length at Birth

描述(申请人提供)：造血干细胞储备的耗尽，表现为白细胞端粒长度(LTL)的缩短，限制了寿命并增加了心血管疾病的风险。到目前为止，几乎所有关于LTL的研究都集中在成年人身上。然而，最近的证据表明，从受孕到出生影响LTL的因素可能与那些在剩余生命过程中影响LTL的因素一样重要。出生时LTL的个体间差异如此之大，以至于可以与整个成年生命过程中LTL的平均缩短相媲美。此外，怀孕时父亲的年龄较高 在成年后代中与较长的LTL有关，由于这种影响必须来自父亲的生殖系，这种影响可能在出生时就很明显了。然而，还没有对出生时LTL的决定因素进行严格的研究。这项关于出生时LTL决定因素的前瞻性研究是一项建立在NICHD资助的对未分娩妇女的多点“父母研究”基础上的“辅助研究”。这项辅助研究将在1000名母亲、父亲和婴儿三人中进行。它将以多种方式添加到父研究中的丰富数据数组中，包括收集 1,000名三人组的父亲血液样本和母亲、父亲和婴儿的LTL测量。这项研究的目的是：1)检验父亲受孕年龄(PAC)与出生时LTL的关系；2)检验母亲的暴露和条件是否是出生时LTL的决定因素；3)比较出生时LTL的性别、种族/民族和社会经济地位；4)探讨胎儿生长速度与出生时LTL的关系。这项研究将建立一个平台或进一步的研究，包括遗传和表观遗传对出生时LTL的影响以及LTL在儿童早期的变化。通过确定出生时LTL的决定因素，这项研究将为将从受孕到分娩的经历与健康和长寿联系起来提供基础 在以后的生活中。此外，这项研究有可能改变人们对人口健康的理解，因为它开启了对宫内经历从生物学上嵌入个人体质的途径的新调查，并可能反映在儿童时期出现并随后演变的疾病风险因素中。 公共卫生相关性：关于成人端粒长度(由白细胞端粒长度或LTL测量)及其在心血管疾病和长寿中的重要作用，人们知道得很多，但对出生时的LTL知之甚少。然而，我们确实知道，个体在出生时LTL的差异很大，这项研究调查了出生前的暴露(如母亲暴露和受孕时的父亲年龄)是否解释了出生时LTL的差异。这一结果将帮助我们了解生命早期干预(甚至早在产前护理)是否可以在以后的生活中改善人群的健康。

DESCRIPTION (provided by applicant): Depletion of hematopoietic stem cell reserves, expressed as the shortening of leukocyte telomere length (LTL), sets a limit on longevity and increases the risk of cardiovascular disease. Until now, almost all research on LTL has focused on adults. Recent evidence suggests, however, that the factors which influence LTL from conception to birth could be as important as those which influence LTL over the remainder of the life course. The inter-individual variation in LTL at birth is so large that it rivals the averge shortening of LTL over the entire adult life course. In addition, higher paternal age at conception is associated with longer LTL in adult offspring, and since this effect must derive from the paternal germ line, it may be evident by the time of birth. However, no rigorous study has been done of the determinants of LTL at birth. This prospective investigation of the determinants of LTL at birth is an "ancillary study" which builds on a multisite NICHD-funded "parent study" of nulliparous women. The ancillary study will be done in 1,000 trios of mother, father, and baby. It will add to the rich array of data in the parent study in several ways, including the collection of paternal blood samples and the measurement of LTL in mothers, fathers, and babies for the 1,000 trios. The Aims of the study are to: 1) examine the relation of paternal age at conception (PAC) to LTL at birth, 2) examine whether maternal exposures and conditions are determinants of LTL at birth, 3) compare LTL at birth across sex, race/ethnicity and socioeconomic status, and 4) explore the relation of fetal growth rate to LTL at birth. This study will build a platform or further investigations including genetic and epigenetic influences on LTL at birth and changes in LTL during early childhood years. By identifying the determinants of LTL at birth, this research will provide a foundation for linking experience from conception to birth with health and longevity in later life. Moreover, this research has the potential to transform understanding of population health by opening novel investigations of the pathways through which intra-uterine experiences are biologically embedded in the individual's constitution, and might be reflected in risk factors for disease which emerge in childhood and evolve thereafter. PUBLIC HEALTH RELEVANCE: Much is known about telomere length (measured by leukocyte telomere length or LTL) in adults, and its important role in cardiovascular disease and longevity, but very little is known about LTL at birth. We do know, however, that individuals vary widely in LTL at birth, and this study examines whether exposures before birth (such as maternal exposures and paternal age at conception) explain the variation in LTL at birth. The results will help us understand whether interventions early in life (even as early as prenatal care) could improve the health of the population in later life.