ArticleGenome biology2019
Screening for genes that accelerate the epigenetic aging clock in humans reveals a role for the H3K36 methyltransferase NSD1.
Article in Genome biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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59 citing papers in PubMed, 121 citations in OpenAlex.
- Disease-associated mutations directionally modulate epigenetic age in iPSC-derived tissues.bioRxiv : the preprint server for biology · 2026Article
- NSD1 governs H3K36me2-mediated DNA methylation and drives endo-mesodermal differentiation of human iPSCs.Clinical epigenetics · 2026Article
- Multi-tissue transcriptomic aging atlas reveals predictive aging biomarkers in the killifish.Nature aging · 2026Article
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- Identification of genetic and non-genetic modifiers of genomic imprinting through screening of imprinted DMR methylation in humans.Epigenetics & chromatin · 2025Article
- Epigenetic ageing clocks: statistical methods and emerging computational challenges.Nature reviews. Genetics · 2025Review
- A novel framework to build saliva-based DNA methylation biomarkers: Quantifying systemic chronic inflammation as a case study.Aging cell · 2025Article
- DNA methylation biomarkers of intellectual/developmental disability across the lifespan.Journal of neurodevelopmental disorders · 2025Review
- An exploratory analysis of bezisterim treatment associated with decreased biological age acceleration, and improved clinical measure and biomarker changes in mild-to-moderate probable Alzheimer's disease.Frontiers in neuroscience · 2025Article
- Higher order interaction analysis quantifies coordination in the epigenome revealing novel biological relationships in Kabuki syndrome.Briefings in bioinformatics · 2024Article
- Pan-cancer analysis of m1A writer gene RRP8: implications for immune infiltration and prognosis in human cancers.Discover oncology · 2024Article
- A comprehensive map of the aging blood methylome in humans.Genome biology · 2024Article
- HDAC4 influences the DNA damage response and counteracts senescence by assembling with HDAC1/HDAC2 to control H2BK120 acetylation and homology-directed repair.Nucleic acids research · 2024Article
- Spatiotemporal transcriptomic profiling and modeling of mouse brain at single-cell resolution reveals cell proximity effects of aging and rejuvenation.bioRxiv : the preprint server for biology · 2024Article
- Quantifying the stochastic component of epigenetic aging.Nature aging · 2024Article
- Identification of Novel NSD1 variations in four Pediatric cases with sotos Syndrome.BMC medical genomics · 2024Article
- Integrative multi-omics analysis reveals the critical role of the PBXIP1 gene in Alzheimer's disease.Aging cell · 2024Article
- Article
- An Updated Review on the Significance of DNA and Protein Methyltransferases and De-methylases in Human Diseases: From Molecular Mechanism to Novel Therapeutic Approaches.Current medicinal chemistry · 2024Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundEpigenetic clocks are mathematical models that predict the biological age of an individual using DNA methylation data and have emerged in the last few years as the most accurate biomarkers of the aging process. However, little is known about the molecular mechanisms that control the rate of such clocks. Here, we have examined the human epigenetic clock in patients with a variety of developmental disorders, harboring mutations in proteins of the epigenetic machinery.
resultsUsing the Horvath epigenetic clock, we perform an unbiased screen for epigenetic age acceleration in the blood of these patients. We demonstrate that loss-of-function mutations in the H3K36 histone methyltransferase NSD1, which cause Sotos syndrome, substantially accelerate epigenetic aging. Furthermore, we show that the normal aging process and Sotos syndrome share methylation changes and the genomic context in which they occur. Finally, we found that the Horvath clock CpG sites are characterized by a higher Shannon methylation entropy when compared with the rest of the genome, which is dramatically decreased in Sotos syndrome patients.
conclusionsThese results suggest that the H3K36 methylation machinery is a key component of the epigenetic maintenance system in humans, which controls the rate of epigenetic aging, and this role seems to be conserved in model organisms. Our observations provide novel insights into the mechanisms behind the epigenetic aging clock and we expect will shed light on the different processes that erode the human epigenetic landscape during aging.
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