Leukocyte Telomere Length in Newborns: Implications for the Role of Telomeres in Human Disease

被引:178
作者
Factor-Litvak, Pam [1 ]
Susser, Ezra [1 ,3 ]
Kezios, Katrina [1 ]
McKeague, Ian [2 ]
Kark, Jeremy D. [4 ]
Hoffman, Matthew [5 ]
Kimura, Masayuki [6 ]
Wapner, Ronald [7 ]
Aviv, Abraham [6 ]
机构
[1] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA
[2] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA
[3] New York State Psychiat Inst & Hosp, New York, NY 10032 USA
[4] Hebrew Univ Jerusalem, Hadassah Sch Publ Hlth & Community Med, Jerusalem, Israel
[5] Christiana Care Hlth Syst, Dept Obstet & Gynecol, Newark, DE USA
[6] Rutgers State Univ, New Jersey Med Sch, Ctr Human Dev & Aging, Newark, NJ 07103 USA
[7] Columbia Univ, Coll Phys & Surg, Dept Obstet & Gynecol, New York, NY USA
基金
美国国家卫生研究院;
关键词
PATERNAL AGE; SOUTHERN BLOTS; LUNG-CANCER; RISK; ASSOCIATION; MORTALITY; HERITABILITY; METAANALYSIS; POPULATION; HEALTH;
D O I
10.1542/peds.2015-3927
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
BACKGROUND AND OBJECTIVE: In adults, leukocyte telomere length (LTL) is variable, familial, and longer in women and in offspring conceived by older fathers. Although short LTL is associated with atherosclerotic cardiovascular disease, long LTL is associated with major cancers. The prevailing notion is that LTL is a "telomeric clock," whose movement (expressed in LTL attrition) reflects the pace of aging. Accordingly, individuals with short LTL are considered to be biologically older than their peers. Recent studies suggest that LTL is largely determined before adulthood. We examined whether factors that largely characterize LTL in adults also influence LTL in newborns. METHODS: LTL was measured in blood samples from 490 newborns and their parents. RESULTS: LTL (mean +- SD) was longer (9.50 +/- 0.70 kb) in newborns than in their mothers (7.92 +/- 0.67 kb) and fathers (7.70 +/- 0.71 kb) (both P < .0001); there was no difference in the variance of LTL among the 3 groups. Newborn LTL correlated more strongly with age-adjusted LTL in mothers (r = 0.47; P < .01) than in fathers (r = 0.36; P < .01) (P for interaction = .02). Newborn LTL was longer by 0.144 kb in girls than in boys (P = .02), and LTL was longer by 0.175 kb in mothers than in fathers (P < .0001). For each 1-year increase in father's age, newborn LTL increased by 0.016 kb (95% confidence interval: 0.04 to 0.28) (P = .0086). CONCLUSIONS: The large LTL variation across newborns challenges the telomeric clock model. Having inherently short or long LTL may be largely determined at birth, anteceding by decades disease manifestation in adults.
引用
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页数:9
相关论文
共 48 条
[1]   Telomere length in small-for-gestational-age babies [J].
Akkad, A ;
Hastings, R ;
Konje, JC ;
Bell, SC ;
Thurston, H ;
Williams, B .
BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, 2006, 113 (03) :318-323
[2]   Telomere length and risk of melanoma, squamous cell carcinoma, and basal cell carcinoma [J].
Anic, Gabriella M. ;
Sondak, Vernon K. ;
Messina, Jane L. ;
Fenske, Neil A. ;
Zager, Jonathan S. ;
Cherpelis, Basil S. ;
Lee, Ji-Hyun ;
Fulp, William J. ;
Epling-Burnette, Pearlie K. ;
Park, Jong Y. ;
Rollison, Dana E. .
CANCER EPIDEMIOLOGY, 2013, 37 (04) :434-439
[3]   Collapse of Telomere Homeostasis in Hematopoietic Cells Caused by Heterozygous Mutations in Telomerase Genes [J].
Aubert, Geraldine ;
Baerlocher, Gabriela M. ;
Vulto, Irma ;
Poon, Steven S. ;
Lansdorp, Peter M. .
PLOS GENETICS, 2012, 8 (05)
[4]   Telomeres, Atherosclerosis, and Human Longevity A Causal Hypothesis [J].
Aviv, Abraham ;
Kark, Jeremy D. ;
Susser, Ezra .
EPIDEMIOLOGY, 2015, 26 (03) :295-299
[5]   Leukocyte Telomere Length and the Father's Age Enigma: Implications for Population Health and for Life Course [J].
Aviv, Abraham ;
Susser, Ezra .
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 2013, 42 (02) :457-462
[6]   Impartial comparative analysis of measurement of leukocyte telomere length/DNA content by Southern blots and qPCR [J].
Aviv, Abraham ;
Hunt, Steven C. ;
Lin, Jue ;
Cao, Xiaojian ;
Kimura, Masayuki ;
Blackburn, Elizabeth .
NUCLEIC ACIDS RESEARCH, 2011, 39 (20)
[7]   Potential roles for estrogen regulation of telomerase activity in aging [J].
Bayne, Sharyn ;
Jones, Margaret E. E. ;
Ll, He ;
Liu, Jun-Ping .
HEALTHY AGING AND LONGEVITY, 2007, 1114 :48-55
[8]   Tracking and fixed ranking of leukocyte telomere length across the adult life course [J].
Benetos, Athanase ;
Kark, Jeremy D. ;
Susser, Ezra ;
Kimura, Masayuki ;
Sinnreich, Ronit ;
Chen, Wei ;
Steenstrup, Troels ;
Christensen, Kaare ;
Herbig, Utz ;
Hjelmborg, Jacob von Bornemann ;
Srinivasan, Sathanur R. ;
Berenson, Gerald S. ;
Labat, Carlos ;
Aviv, Abraham .
AGING CELL, 2013, 12 (04) :615-621
[9]   Meta-analysis of telomere length in 19 713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect [J].
Broer, Linda ;
Codd, Veryan ;
Nyholt, Dale R. ;
Deelen, Joris ;
Mangino, Massimo ;
Willemsen, Gonneke ;
Albrecht, Eva ;
Amin, Najaf ;
Beekman, Marian ;
de Geus, Eco J. C. ;
Henders, Anjali ;
Nelson, Christopher P. ;
Steves, Claire J. ;
Wright, Margie J. ;
de Craen, Anton J. M. ;
Isaacs, Aaron ;
Matthews, Mary ;
Moayyeri, Alireza ;
Montgomery, Grant W. ;
Oostra, Ben A. ;
Vink, Jacqueline M. ;
Spector, Tim D. ;
Slagboom, P. Eline ;
Martin, Nicholas G. ;
Samani, Nilesh J. ;
van Duijn, Cornelia M. ;
Boomsma, Dorret I. .
EUROPEAN JOURNAL OF HUMAN GENETICS, 2013, 21 (10) :1163-1168
[10]   Leukocyte Telomere Length and Risks of Incident Coronary Heart Disease and Mortality in a Racially Diverse Population of Postmenopausal Women [J].
Carty, Cara L. ;
Kooperberg, Charles ;
Liu, Jingmin ;
Herndon, Megan ;
Assimes, Themistocles ;
Hou, Lifang ;
Kroenke, Candyce H. ;
LaCroix, Andrea Z. ;
Kimura, Masayuki ;
Aviv, Abraham ;
Reiner, Alexander P. .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2015, 35 (10) :2225-2231