期刊
AGING CELL
卷 14, 期 4, 页码 669-677出版社
WILEY
DOI: 10.1111/acel.12347
关键词
aging; genetics; human; parental effects; secular trend; telomeres; telomerase; telomere length
资金
- Wellcome Trust
- European Community
- National Institute for Health Research (NIHR) BioResource Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London
- National Heart, Lung, and Blood Institute [U01 HL56563, U01 HL56564, U01 HL56565, U01 HL56566, U01 HL56567, U01 HL56568, U01 HL56569]
- FWO-Flanders research grants [G.0427.03, G.0838.10N]
- Simmons Cancer Center Support Grant [5P30 CA142543]
- Southland Financial Corporation Distinguished Chair in Geriatric Research
- National Institute of Health [C06 RR30414]
- National Institute for Health Research [NF-SI-0514-10027] Funding Source: researchfish
- NATIONAL CANCER INSTITUTE [P50CA070907, P30CA142543, R13CA113094] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [C06RR030414] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [U01HL056569, U01HL056568, U01HL056567, U01HL056563, U01HL056564, U01HL056566, U01HL056565] Funding Source: NIH RePORTER
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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