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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD071180-03
Application #
8632834
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Reddy, Uma M
Project Start
2012-04-01
Project End
2017-02-28
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
3
Fiscal Year
2014
Total Cost
$644,295
Indirect Cost
$148,500
Name
Columbia University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Ding, Zhihao; Mangino, Massimo; Aviv, Abraham et al. (2014) Estimating telomere length from whole genome sequence data. Nucleic Acids Res 42:e75
Subramanian, Subha; Liu, Chunyu; Aviv, Abraham et al. (2014) Stromal cell-derived factor 1 as a biomarker of heart failure and mortality risk. Arterioscler Thromb Vasc Biol 34:2100-5
Elbers, Clara C; Garcia, Melissa E; Kimura, Masayuki et al. (2014) Comparison between southern blots and qPCR analysis of leukocyte telomere length in the health ABC study. J Gerontol A Biol Sci Med Sci 69:527-31
Daniali, Lily; Benetos, Athanase; Susser, Ezra et al. (2013) Telomeres shorten at equivalent rates in somatic tissues of adults. Nat Commun 4:1597
Aviv, Abraham; Susser, Ezra (2013) Leukocyte telomere length and the father's age enigma: implications for population health and for life course. Int J Epidemiol 42:457-62