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Genetic determination of telomere size in humans: A twin study of three age groups

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Author: Slagboom, P.E. · Droog, S. · Boomsma, D.I.
Type:article
Date:1994
Institution: TNO Preventie en Gezondheid
Source:American Journal of Human Genetics, 5, 55, 876-882
Identifier: 232706
Keywords: Health · agar gel electrophoresis · autoradiography · blood sampling · cohort analysis · dna determination · genetic model · genetic variability · heritability · image analysis · major clinical study · maximum likelihood method · priority journal · restriction fragment · southern blotting · tandem repeat · twin zygosity · twins · Adolescent · Adult · Aged · Aged, 80 and over · Aging · Blotting, Southern · Child · Child, Preschool · Human · Middle Age · Repetitive Sequences, Nucleic Acid · Telomere

Abstract

Reduction of telomere length has been postulated to be a causal factor in cellular aging. Human telomeres terminate in tandemly arranged repeat arrays consisting of the (TTAGGG) motif. The length of these arrays in cells from human mitotic tissues is inversely related to the age of the donor, indicating telomere reduction with age. In addition to telomere length differences between different age cohorts, considerable variation is present among individuals of the same age. To investigate whether this variation can be ascribed to genetic influences, we have measured the size of terminal restriction fragments (TRFs) in HaeIII-digested genomic DNA from 123 human MZ and DZ twin pairs 2-95 years of age. The average rate of telomere shortening was 31 bp/year, which is similar to that observed by others. Statistical analysis in 115 pairs 2-63 years of age indicates a 78% heritability for mean TRF length in this age cohort. The individual differences in mean TRF length in blood, therefore, seem to a large extent to be genetically determined.