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

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

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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 crosssectional 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.

Original languageEnglish (US)
Pages (from-to)669-677
Number of pages9
JournalAging Cell
Volume14
Issue number4
DOIs
StatePublished - 2015

Keywords

  • Aging
  • Genetics
  • Human
  • Parental effects
  • Secular trend
  • Telomerase
  • Telomere length
  • Telomeres

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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