Heritability of telomere length in a study of long-lived families

Lawrence S. Honig, Min Suk Kang, Rong Cheng, John H. Eckfeldt, Bharat Thyagarajan, Catherine Leiendecker-Foster, Michael A. Province, Jason L. Sanders, Thomas Perls, Kaare Christensen, Joseph H. Lee, Richard Mayeux, Nicole Schupf

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


Chromosomal telomere length shortens with repeated cell divisions. Human leukocyte DNA telomere length (LTL) has been shown to shorten during aging. LTL shortening has correlated with decreased longevity, dementia, and other age-associated processes. Because LTL varies widely between individuals in a given age group, it has been hypothesized to be a marker of biological aging. However, the principal basis for the variation of human LTL has not been established, although various studies have reported heritability. Here, we use a family-based study of longevity to study heritability of LTL in 3037 individuals. We show that LTL is shorter in older individuals, and in males, and has a high heritability (overall h2 = 0.54). In the offspring generation, who are in middle-life, we find an ordinal relationship: persons more-closely-related to elderly probands have longer LTL than persons less-closely-related, who nonetheless have longer LTL than unrelated spouses of the offspring generation. These results support a prominent genetic underpinning of LTL. Elucidation of such genetic bases may provide avenues for intervening in the aging process.

Original languageEnglish (US)
Pages (from-to)2785-2790
Number of pages6
JournalNeurobiology of Aging
Issue number10
StatePublished - Oct 1 2015

Bibliographical note

Funding Information:
The LLFS study is funded by the National Institute on Aging and involves collaboration with the Center for Medicare and Medicaid Services via an Interagency Agreement, a Data Management and Coordinating Center at Washington University St. Louis, a laboratory coordinating site at the University of Minnesota, and 4 clinical centers: Boston University, Columbia University, the University of Pittsburgh, and the University of Southern Denmark. Long-lived individuals, their siblings, and their offspring were recruited, and a referent group consisting of the spouses, primarily of the offspring generation, was also recruited and examined. In the United States, recruitment involved mailings to elderly people (at least 79 year olds in the initial phase, then in later phase, people at least 89 years old) who on January 1, 2005 had neither end-stage renal disease nor were in a hospice program but did live within 3 hours driving distance of 1 of the 3 United States study centers. There was also community recruitment using Web-based media, newspaper advertisements, and community presentations. In Denmark, the Danish National Register was used to identify individuals aged 90 years and above during the study recruitment period ( Pedersen et al., 2006 ), and then archives were searched to locate the parents of the elderly individuals to identify potentially eligible sibships, who were then contacted regarding participation in the LLFS using criteria parallel to those used in the United States. Overall, 32.9% of the offspring generation was Danish. The Institutional Review Boards at each of the institutions in the United States and the regional ethical committee in Denmark reviewed and approved this project.

Funding Information:
The LLFS study is sponsored by the US National Institute on Aging / National Institutes of Health : NIA/NIH cooperative agreements U01AG023712 , U01AG23744 , U01AG023746 , U01AG023749 , and U01AG023755 . The Danish Aging Research Center is funded by the VELUX Foundation . The authors acknowledge the contributions of the NIA Geriatrics and Clinical Gerontology Program including Drs. Evan C. Hadley, Winifred Rossi, and Nalini Raghavachari. The authors also acknowledge the support of NIA/NIH grant P50AG008702 (to Scott Small), the Henry Panasci Fund , and the Taub Institute for Research on Alzheimer's disease and the Aging Brain.

Publisher Copyright:
© 2015 Elsevier Inc.


  • Aging
  • Heritability
  • Longevity
  • Telomere


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