title: Decreasing initial telomere length in humans intergenerationally understates age-associated telomere shortening.
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.
authors.affiliation: Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Brody
authors.initials: B
authors.lastname: Holohan
authors.affiliation: Department of Mathematical Modeling, Statistics and Bioinformatics, University of Ghent, Ghent, 9000, Belgium.
authors.forename: Tim
authors.initials: T
authors.lastname: De Meyer
authors.affiliation: Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Batten
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, King's College London St. Thomas' Hospital Campus South Wing, Block D, 3rd Floor Westminster Bridge Road, London, SE1 7EH, London, UK.|NIHR Biomedical Research Centre at Guy's and St. Thomas' Foundation Trust, King's College London St. Thomas' Hospital Campus South Wing, Block D, 3rd Floor Westminster Bridge Road, London, SE1 7EH, London, UK.
authors.forename: Massimo
authors.initials: M
authors.lastname: Mangino
authors.affiliation: Cardiovascular Genetics Division, Department of Internal Medicine, University of Utah, Salt Lake City, UT, 84108, USA.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Hunt
authors.affiliation: Bimetra, Clinical Research Center Ghent, Ghent University Hospital, Ghent, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: Bekaert
authors.affiliation: Department of Cardiovascular Diseases, Ghent University Hospital, Ghent University, Ghent, Belgium.
authors.forename: Marc L
authors.initials: ML
authors.lastname: De Buyzere
authors.affiliation: Department of Cardiovascular Diseases, Ghent University Hospital, Ghent University, Ghent, Belgium.
authors.forename: Ernst R
authors.initials: ER
authors.lastname: Rietzschel
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, King's College London St. Thomas' Hospital Campus South Wing, Block D, 3rd Floor Westminster Bridge Road, London, SE1 7EH, London, UK.
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
authors.affiliation: Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Woodring E
authors.initials: WE
authors.lastname: Wright
authors.affiliation: Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.|Center for Excellence in Genomics Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Jerry W
authors.initials: JW
authors.lastname: Shay
mesh_terms: D000375:Aging / Q000235:genetics*; D003430:Cross-Sectional Studies; D066264:Datasets as Topic; D005260:Female; D015870:Gene Expression; D006801:Humans; D040582:Inheritance Patterns; D008137:Longitudinal Studies; D008297:Male; D010331:Paternal Age; D019098:Telomerase / Q000235:genetics*; D016615:Telomere / Q000737:chemistry / Q000235:genetics*; D059505:Telomere Homeostasis; D059506:Telomere Shortening
chemical_list: C509186:TERT protein, human; D019098:Telomerase
keywords: aging; genetics; human; parental effects; secular trend; telomerase; telomere length; telomeres