Telomere length is paternally inherited and is associated with parental lifespan

Omer T. Njajou; Richard M. Cawthon; Coleen M. Damcott; Shih-Hsuan Wu; Sandy Ott; Michael J. Garant; Elizabeth H. Blackburn; Braxton D. Mitchell; Alan R. Shuldiner; Wen-Chi Hsueh

doi:10.1073/pnas.0702703104

Edited by Victor A. McKusick, Johns Hopkins University School of Medicine, Baltimore, MD, and approved June 7, 2007 (received for review March 23, 2007)

Abstract

Telomere length (TL) is emerging as a biomarker for aging and survival. To evaluate factors influencing this trait, we measured TL in a large homogeneous population, estimated the heritability (h²), and tested for parental effects on TL variation. Our sample included 356 men and 551 women, aged 18–92 years, from large Amish families. Mean TL in leukocytes was measured by quantitative PCR (mean: 6,198 ± 1,696 bp). The h² of TL was 0.44 ± 0.06 (P < 0.001), after adjusting for age, sex, and TL assay batch. As expected, TL was negatively correlated with age (r = −0.40; P < 0.001). There was no significant difference in TL between men and women, consistent with our previous findings that Amish men lived as long as Amish women. There was a stronger and positive correlation and association between TL in the offspring and paternal TL (r = 0.46, P < 0.001; β = 0.22, P = 0.006) than offspring and maternal TL (r = 0.18, P = 0.04; β = −0.02, P = 0.4). Furthermore, we observed a positive correlation and association between daughter's TL and paternal lifespan (r = 0.20, P < 0.001; β = 0.21, P = 0.04), but not between daughter's TL and maternal lifespan (r = −0.01, β = 0.04; both P = not significant). Our data, which are based on one of the largest family studies of human TL, support a link between TL and aging and lifespan and suggest a strong genetic influence, possibly via an imprinting mechanism, on TL regulation.

Footnotes

^‖To whom correspondence should be addressed. E-mail: wen-chi.hsueh{at}ucsf.edu
Author contributions: O.T.N., R.M.C., E.H.B., B.D.M., A.R.S., and W.-C.H. designed research; O.T.N., R.M.C., C.M.D., S.O., B.D.M., and W.-C.H. performed research; M.J.G. contributed new reagents/analytic tools; O.T.N., S.-H.W., A.R.S., and W.-C.H. analyzed data; and O.T.N. and W.-C.H. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Abbreviations:
TL,
telomere length;
OOA,
Old Order Amish;
h2,
heritability estimate;
Q-PCR,
quantitative PCR.
© 2007 by The National Academy of Sciences of the USA