Decreasing initial telomere length in humans intergenerationally understates age‐associated telomere shortening

Aging Cell

Brody Holohan⁴  Tim De Meyer²  Kimberly Batten⁴  Massimo Mangino³  Steven C. Hunt⁵  Sofie Bekaert⁶  Marc L. De Buyzere¹  Ernst R. Rietzschel¹  Tim D. Spector³  Woodring E. Wright⁴ 

[1] Department of Cardiovascular Diseases, Ghent University Hospital, Ghent University, Ghent, Belgium;Department of Mathematical Modeling, Statistics and Bioinformatics, University of Ghent, Ghent, Belgium;Department of Twin Research and Genetic Epidemiology, King's College London, London, London, UK;Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX, USA;Cardiovascular Genetics Division, Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA;Bimetra, Clinical Research Center Ghent, Ghent University Hospital, Ghent, Belgium

关键词: aging;    genetics;    human;    parental effects;    secular trend;    telomeres;    telomerase;    telomere length;   

DOI  :  10.1111/acel.12347

来源: Wiley

【 摘 要 】

Summary

Telomere length shortens with aging, and short telomeres have been linked to a wide variety of pathologies. Previous studies suggested a discrepancy in age-associated telomere shortening rate estimated by cross-sectional studies versus the rate measured in longitudinal studies, indicating a potential bias in cross-sectional estimates. Intergenerational changes in initial telomere length, such as that predicted by the previously described effect of a father's age at birth of his offspring (FAB), could explain the discrepancy in shortening rate measurements. We evaluated whether changes occur in initial telomere length over multiple generations in three large datasets and identified paternal birth year (PBY) as a variable that reconciles the difference between longitudinal and cross-sectional measurements. We also clarify the association between FAB and offspring telomere length, demonstrating that this effect is substantially larger than reported in the past. These results indicate the presence of a downward secular trend in telomere length at birth over generational time with potential public health implications.

【 授权许可】

CC BY   
© 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.