Determinants of Leukocyte Telomere Length at Birth

出生时白细胞端粒长度的决定因素

基本信息

批准号：
9022327
负责人：
ABRAHAM AVIV
金额：
$ 64.7万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-04-01 至 2019-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9022327
关键词：
Adolescence Adult Adult Children Affect Age Ancillary Study Archives Area Behavior Biological Biological Markers Biology Birth Blood specimen Cardiovascular Diseases Cell division Characteristics Childhood Cognition Collection Conceptions Constitution DNA Methylation Data Development Disease Early Intervention Elderly Ensure Epigenetic Process Ethnic Origin Evaluation Fathers Fetal Growth First Pregnancy Trimester Foundations Funding Future Genes Genetic Germ Lines Gestational Diabetes Growth Health Health behavior Hematopoietic stem cells Human Human Biology Individual Investigation Isoprostanes Length Leukocytes Life Life Cycle Stages Life Style Link Longevity Maternal Exposure Measurement Measures Mediating Mental Depression Methylation Modality Mothers Mutation National Institute of Child Health and Human Development Newborn Infant Obesity Outcome Oxidative Stress Parents Paternal Age Pathway interactions Perinatal Exposure Placenta Pre-Eclampsia Pregnancy Prenatal care Preventive Protocols documentation Race Research Research Infrastructure Risk Factors Role Sampling Science Site Smoking Socioeconomic Status Specimen Stress Therapeutic Time Toxic Environmental Substances Ultrasonography Umbilical Cord Blood Variant Weight Gain Woman Work age related cardiovascular disorder risk cohort critical period disorder risk early childhood experience father role fetal blood follow-up improved inter-individual variation novel population health pregnancy hypertension prenatal exposure prospective sex telomere

项目摘要

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.

描述（由申请人提供）：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，影响从受孕到出生的 LTL 的因素可能与影响生命历程剩余时间的 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，父亲受孕年龄较高与成年后代较长的 LTL 相关，并且由于这种效应必须来自父本种系，因此在出生时可能会很明显。然而，尚未对出生时 LTL 的决定因素进行严格的研究。这项对出生时 LTL 决定因素的前瞻性调查是一项“辅助研究”，它建立在 NICHD 资助的针对未产妇的多地点“父母研究”的基础上。辅助研究将在 1,000 名母亲、父亲和婴儿三人组中进行。它将通过多种方式添加到父研究中丰富的数据中，包括收集 1,000 名三人的父亲血液样本以及母亲、父亲和婴儿的 LTL 测量。该研究的目的是：1）检查父亲受孕年龄（PAC）与出生时LTL的关系，2）检查母亲的暴露和条件是否是出生时LTL的决定因素，3）比较不同性别的出生时LTL，种族/民族和社会经济地位，4) 探讨胎儿生长速率与出生时 LTL 的关系。这项研究将建立一个平台或进一步研究，包括遗传和表观遗传对出生时 LTL 的影响以及儿童早期 LTL 的变化。通过确定出生时 LTL 的决定因素，这项研究将为将受孕到出生的经历与健康和长寿联系起来奠定基础在以后的生活中。此外，这项研究有可能通过对子宫内经历在生物学上嵌入个人体质的途径进行新的研究，从而改变对人口健康的理解，并可能反映在儿童时期出现并随后演变的疾病的危险因素中。。

项目成果

期刊论文数量（16）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Ancestry, Telomere Length, and Atherosclerosis Risk.

祖先、端粒长度和动脉粥样硬化风险。

DOI：
发表时间：
2017
期刊：
影响因子：
0
作者：
Benetos, Athanase;Aviv, Abraham
通讯作者：
Aviv, Abraham

Telomeres and replicative cellular aging of the human placenta and chorioamniotic membranes.

人类胎盘和绒毛膜羊膜的端粒和复制细胞老化。

DOI：
发表时间：
2021
期刊：
影响因子：
4.6
作者：
Lai, Tsung;Simpson, Mark;Patel, Krunal;Verhulst, Simon;Noh, Jungsik;Roche, Natalie;Heller, Debra;Guirguis, George;Shay, Jerry W;Herbig, Utz;Aviv, Abraham
通讯作者：
Aviv, Abraham

The mitochondrial genome, paternal age and telomere length in humans.

人类线粒体基因组、父亲年龄和端粒长度。