title: Heritability of telomere length in a study of long-lived families.
abstract: 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 h(2) = 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.
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY, USA; Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY, USA; Department of Neurology, Columbia University Medical Center, New York, NY, USA. Electronic address: LH456@CUMC.COLUMBIA.EDU.
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Honig
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY, USA.
authors.forename: Min Suk
authors.initials: MS
authors.lastname: Kang
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Cheng
authors.affiliation: Department Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Eckfeldt
authors.affiliation: Department Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Bharat
authors.initials: B
authors.lastname: Thyagarajan
authors.affiliation: Department Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Leiendecker-Foster
authors.affiliation: Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Province
authors.affiliation: Department of Epidemiology, Center for Aging and Population Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Jason L
authors.initials: JL
authors.lastname: Sanders
authors.affiliation: Section of Geriatrics, Department of Medicine, Boston Medical Center, Boston, MA, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Perls
authors.affiliation: The Danish Aging Research Center, University of Southern Denmark, Odense, Denmark.
authors.forename: Kaare
authors.initials: K
authors.lastname: Christensen
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY, USA; Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY, USA; Department of Epidemiology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY, USA; Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY, USA; Department of Neurology, Columbia University Medical Center, New York, NY, USA; Department of Epidemiology, Columbia University Medical Center, New York, NY, USA; Department of Psychiatry, Columbia University Medical Center, New York, NY, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Mayeux
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY, USA; Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY, USA; Department of Psychiatry, Columbia University Medical Center, New York, NY, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Schupf
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics; D004247:DNA / Q000235:genetics*; D005260:Female; D006801:Humans; D007962:Leukocytes; D008136:Longevity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D059505:Telomere Homeostasis / Q000235:genetics*
chemical_list: D004247:DNA
keywords: Aging; Heritability; Longevity; Telomere