Decreasing initial telomere length in humans intergenerationally understates age‐associated telomere shortening |
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| Authors: | Brody Holohan Tim De Meyer Kimberly Batten Massimo Mangino Steven C Hunt Sofie Bekaert Marc L De Buyzere Ernst R Rietzschel Tim D Spector Woodring E Wright Jerry W Shay |
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| Institution: | 1. Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX, USA;2. Department of Mathematical Modeling, Statistics and Bioinformatics, University of Ghent, Ghent, Belgium;3. Department of Twin Research and Genetic Epidemiology, King's College London, London, London, UK;4. NIHR Biomedical Research Centre at Guy's and St. Thomas’ Foundation Trust, London, London, UK;5. Cardiovascular Genetics Division, Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA;6. Bimetra, Clinical Research Center Ghent, Ghent University Hospital, Ghent, Belgium;7. Department of Cardiovascular Diseases, Ghent University Hospital, Ghent University, Ghent, Belgium;8. Center for Excellence in Genomics Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia |
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| Abstract: | 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. |
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| Keywords: | aging genetics human parental effects secular trend telomeres telomerase telomere length |
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