Paternal age and telomere length in twins: the germ stem cell selection paradigm

Telomere length, a highly heritable trait, is longer in offspring of older fathers. This perplexing feature has been attributed to the longer telomeres in sperm of older men and it might be an ‘epigenetic’ mechanism through which paternal age plays a role in telomere length regulation in humans. Based on two independent (discovery and replication) twin studies, comprising 889 twin pairs, we show an increase in the resemblance of leukocyte telomere length between dizygotic twins of older fathers, which is not seen in monozygotic twins. This phenomenon might result from a paternal age‐dependent germ stem cell selection process, whereby the selected stem cells have longer telomeres, are more homogenous with respect to telomere length, and share resistance to aging.

[1]  B. MacArthur Collective dynamics of stem cell populations , 2014, Proceedings of the National Academy of Sciences.

[2]  T. Spector,et al.  Meta-analysis of telomere length in 19 713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect , 2013, European Journal of Human Genetics.

[3]  C. Walter,et al.  The Paternal Age Effect: A Multifaceted Phenomenon , 2013, Biology of reproduction.

[4]  E. Susser,et al.  Telomeres shorten at equivalent rates in somatic tissues of adults , 2013, Nature Communications.

[5]  S. Steinberg,et al.  Rate of de novo mutations and the importance of father’s age to disease risk , 2012, Nature.

[6]  E. Susser,et al.  Divergence of sperm and leukocyte age-dependent telomere dynamics: implications for male-driven evolution of telomere length in humans , 2012, Molecular human reproduction.

[7]  P. Lansdorp,et al.  Collapse of Telomere Homeostasis in Hematopoietic Cells Caused by Heterozygous Mutations in Telomerase Genes , 2012, PLoS genetics.

[8]  C. Harley,et al.  Measurement of telomere length by the Southern blot analysis of terminal restriction fragment lengths , 2010, Nature Protocols.

[9]  T. Spector,et al.  Offspring's Leukocyte Telomere Length, Paternal Age, and Telomere Elongation in Sperm , 2008, PLoS genetics.

[10]  G. De Backer,et al.  Paternal age at birth is an important determinant of offspring telomere length. , 2007, Human molecular genetics.

[11]  Renuka R. Nayak,et al.  Dynamics of the male germline stem cell population during aging of Drosophila melanogaster , 2006, Aging cell.

[12]  G. Thomas,et al.  Allele-specific relative telomere lengths are inherited , 2006, Human Genetics.

[13]  N. Amso,et al.  Telomere instability in the male germline. , 2006, Human molecular genetics.

[14]  D. Wynford‐Thomas,et al.  Extensive allelic variation and ultrashort telomeres in senescent human cells , 2003, Nature Genetics.

[15]  J. Shay,et al.  Telomerase activity in human germline and embryonic tissues and cells. , 1996, Developmental genetics.

[16]  D I Boomsma,et al.  Genetic determination of telomere size in humans: a twin study of three age groups. , 1994, American journal of human genetics.

[17]  Wen-Hsiung Li,et al.  Male-driven evolution of DNA sequences , 1993, Nature.

[18]  C B Harley,et al.  Telomere length predicts replicative capacity of human fibroblasts. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[19]  J. B. S. Haldane,et al.  The Effect of Variation of Fitness , 1937, The American Naturalist.