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Aging Cell - 2020 - Potabattula - Increasing methylation of sperm rDNA and other repetitive elements in the aging male.pdf (1.47 MB)

Increasing methylation of sperm rDNA and other repetitive elements in the aging male mammalian germline

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submitted on 2024-06-26, 10:37 and posted on 2024-06-27, 06:18 authored by Ramya Potabattula, Federica Zacchini, Grazyna Ewa Ptak, Marcus Dittrich, Tobias Müller, Nady El Hajj, Thomas Hahn, Charis Drummer, Rüdiger Behr, Andrea Lucas‐Hahn, Heiner Niemann, Martin Schorsch, Thomas Haaf

In somatic cells/tissues, methylation of ribosomal DNA (rDNA) increases with age and age‐related pathologies, which has a direct impact on the regulation of nucleolar activity and cellular metabolism. Here, we used bisulfite pyrosequencing and show that methylation of the rDNA transcription unit including upstream control element (UCE), core promoter, 18S rDNA, and 28S rDNA in human sperm also significantly increases with donor's age. This positive correlation between sperm rDNA methylation and biological age is evolutionarily conserved among mammals with widely different life spans such as humans, marmoset, bovine, and mouse. Similar to the tandemly repeated rDNA, methylation of human α‐satellite and interspersed LINE1 repeats, marmoset α‐satellite, bovine alpha‐ and testis satellite I, mouse minor and major satellite, and LINE1‐T repeats increases in the aging male germline, probably related to their sperm histone packaging. Deep bisulfite sequencing of single rDNA molecules in human sperm revealed that methylation does not only depend on donor's age, but also depend on the region and sequence context (A vs. G alleles). Both average rDNA methylation of all analyzed DNA molecules and the number of fully (>50%) methylated alleles, which are thought to be epigenetically silenced, increase with donor's age. All analyzed CpGs in the sperm rDNA transcription unit show comparable age‐related methylation changes. Unlike other epigenetic aging markers, the rDNA clock appears to operate in similar ways in germline and soma in different mammalian species. We propose that sperm rDNA methylation, directly or indirectly, influences nucleolar formation and developmental potential in the early embryo.

Other Information

Published in: Aging Cell
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National Science Centre of Poland (NZ4 03696).

Deutsche Forschungsgemeinschaft (HA1374191).

Horizon2020 Framework Programme (692185).



  • English



Publication Year

  • 2020

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Bin Khalifa University
  • College of Health and Life Sciences - HBKU