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.
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.
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| Aviv, Abraham (2018) The mitochondrial genome, paternal age and telomere length in humans. Philos Trans R Soc Lond B Biol Sci 373: |
| Benetos, Athanase; Kark, Jeremy D; Toupance, Simon et al. (2018) Response by Benetos et al to Letter Regarding Article, ""Short Leukocyte Telomere Length Precedes Clinical Expression of Atherosclerosis: The Blood-and-Muscle Model"". Circ Res 122:e73-e74 |
| Aviv, Abraham; Anderson, James J; Shay, Jerry W (2017) Mutations, Cancer and the Telomere Length Paradox. Trends Cancer 3:253-258 |
| Toupance, Simon; Labat, Carlos; Temmar, Mohamed et al. (2017) Short Telomeres, but Not Telomere Attrition Rates, Are Associated With Carotid Atherosclerosis. Hypertension 70:420-425 |
| Benetos, Athanase; Aviv, Abraham (2017) Ancestry, Telomere Length, and Atherosclerosis Risk. Circ Cardiovasc Genet 10: |
| Factor-Litvak, Pam; Susser, Ezra; Aviv, Abraham (2017) Environmental Exposures, Telomere Length at Birth, and Disease Susceptibility in Later Life. JAMA Pediatr 171:1143-1144 |
| Khan, Sadiya S; Shah, Sanjiv J; Klyachko, Ekaterina et al. (2017) A null mutation in SERPINE1 protects against biological aging in humans. Sci Adv 3:eaao1617 |
| Steenstrup, Troels; Kark, Jeremy D; Verhulst, Simon et al. (2017) Telomeres and the natural lifespan limit in humans. Aging (Albany NY) 9:1130-1142 |
| Verhulst, Simon; Susser, Ezra; Factor-Litvak, Pam R et al. (2016) Response to: Reliability and validity of telomere length measurements. Int J Epidemiol 45:1298-1301 |
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