Delayed paternal age of reproduction in humans is associated with longer telomeres across two generations of descendants

Delayed paternal age of reproduction in humans is associated with longer telomeres across two generations of descendants

1. Dan T. A. Eisenberg^a,^b,^c,¹,
2. M. Geoffrey Hayes^a,^d,^e,², and
3. Christopher W. Kuzawa^a,^b,²

+ Author Affiliations

1. ^aDepartment of Anthropology, Northwestern University, Evanston, IL 60208;
2. ^bCells to Society, The Center on Social Disparities and Health, Institute for Policy Research, Northwestern University, Evanston, IL 60208;
3. ^cDepartment of Anthropology, University of Washington, Seattle, WA 98195;
4. ^dDivision of Endocrinology, Metabolism, and Molecular Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611; and
5. ^eCenter for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611

1. Edited* by Peter T. Ellison, Harvard University, Cambridge, MA, and approved May 11, 2012 (received for review February 7, 2012)

Abstract

Telomeres are repeating DNA sequences at the ends of chromosomes that protect and buffer genes from nucleotide loss as cells divide. Telomere length (TL) shortens with age in most proliferating tissues, limiting cell division and thereby contributing to senescence. However, TL increases with age in sperm, and, correspondingly, offspring of older fathers inherit longer telomeres. Using data and samples from a longitudinal study from the Philippines, we first replicate the finding that paternal age at birth is associated with longer TL in offspring (n = 2,023, P = 1.84 × 10⁻⁶). We then show that this association of paternal age with offspring TL is cumulative across multiple generations: in this sample, grandchildren of older paternal grandfathers at the birth of fathers have longer telomeres (n = 234, P = 0.038), independent of, and additive to, the association of their father’s age at birth with TL. The lengthening of telomeres predicted by each year that the father’s or grandfather’s reproduction are delayed is equal to the yearly shortening of TL seen in middle-age to elderly women in this sample, pointing to potentially important impacts on health and the pace of senescent decline in tissues and systems that are cell-replication dependent. This finding suggests a mechanism by which humans could extend late-life function as average age at reproduction is delayed within a lineage.

• adaptation
• epigenetics
• evolution
• parental effects
• transgenerational plasticity

Footnotes

• ↵¹To whom correspondence should be addressed. E-mail: dtae@dtae.net.
• ↵²M.G.H. and C.W.K. contributed equally to this work.

• Author contributions: D.T.A.E., M.G.H., and C.W.K. designed research; D.T.A.E. performed research; D.T.A.E. analyzed data; and D.T.A.E., M.G.H., and C.W.K. wrote the paper.
• The authors declare no conflict of interest.
• ↵*This Direct Submission article had a prearranged editor.