ArticleAging cell2020
Increasing methylation of sperm rDNA and other repetitive elements in the aging male mammalian germline.
Article in Aging cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Relationship between degree of methylation of sperm long interspersed nuclear element-1 (LINE-1) gene and alteration of sperm parameters and age: a meta-regression analysis.Journal of assisted reproduction and genetics · 2024Pooled it
- Grtp1 Safeguards Against Paternal Reproductive Aging and Intergenerational Behavioral Deficits by Preserving Redox Homeostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Pathogenic germline variants in BRCA1/2 are associated with a decreased number of hypomethylated rDNA copies.Breast cancer research : BCR · 2026Article
- Generation of marmoset monkeys with a non-mosaic disruption of the OTOF gene as a model of human deafness.Nature communications · 2026Article
- Sperm rDNA Copy Number and Methylation Are Associated with Male-Factor Infertility.International journal of molecular sciences · 2025Article
- Article
- rDNA Copy Number Variation and Methylation in Human and Mouse Sperm.International journal of molecular sciences · 2025Article
- Article
- Age-related and species-specific methylation changes in the protein-coding marmoset sperm epigenome.Aging cell · 2024Article
- The role of ribosomal DNA methylation in embryonic development, aging and diseases.Epigenetics & chromatin · 2024Review
- Future in the past: paternal reprogramming of offspring phenotype and the epigenetic mechanisms.Archives of toxicology · 2024Review
- Important role of DNA methylation hints at significant potential in tuberculosis.Archives of microbiology · 2024Review
- Ribosomal DNA Copy Number Variation is Coupled with DNA Methylation Changes at the 45S rDNA Locus.Epigenetics · 2023Article
- Effects of paternal and chronological age onAging · 2023Article
- Epigenetic age acceleration in surviving versus deceased COVID-19 patients with acute respiratory distress syndrome following hospitalization.Clinical epigenetics · 2023Article
- Global effects of identity and aging on the human sperm methylome.Clinical epigenetics · 2023Article
- CpG DNA methylation changes during epididymal sperm maturation in bulls.Epigenetics & chromatin · 2023Article
- Biomarkers of aging.Science China. Life sciences · 2023Review
- Does advanced paternal age affect global DNA methylation of human spermatozoa and intracytoplasmic sperm injection outcome?Journal of the Turkish German Gynecological Association · 2023Article
- Article
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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