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

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• 作者：Lawrence S. Honig^a ; ^b ; ^c ; ^{LH456@CUMC.COLUMBIA.EDU" class="auth_mail" title="E-mail the corresponding author} ; Min Suk Kang^a ; Rong Cheng^a ; John H. Eckfeldt^d ; Bharat Thyagarajan^d ; Catherine Leiendecker-Foster^d ; Michael A. Province^e ; Jason L. Sanders^f ; Thomas Perls^g ; Kaare Christensen^h ; Joseph H. Lee^a ; ^b ; ⁱ ; Richard Mayeux^a ; ^b ; ^c ; ⁱ ; ^j ; Nicole Schupf^a ; ^b ; ^j
• 关键词：Telomere ; Heritability ; Longevity ; Aging
• 刊名：Neurobiology of Aging
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：36
• 期：10
• 页码：2785-2790
• 全文大小：454 K

文摘

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.