ArticleNature communications2024
Targeting the hypothalamus for modeling age-related DNA methylation and developing OXT-GnRH combinational therapy against Alzheimer's disease-like pathologies in male mouse model.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Sex differences in neuromodulatory subcortical systems and their implications for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Control of aging-associated neurodegeneration via hypothalamic extracellular vesicles containing parathymosin.Cell reports · 2025Article
- Oxytocin Enhances Demethylation Through TET Enzyme Expression in Neurons of Aged Mice: Oxytocin as a Potential Antiaging Peptide.Aging cell · 2025Article
- A unique polygenic mouse model of obesity exhibits a distinct immunological profile that may offer protection against systemic inflammation, diabetes, and behavioral impairments.Frontiers in immunology · 2025Article
- Deep learning-based classification of peptide analytes from single-channel nanopore translocation events.PloS one · 2025Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
The hypothalamus plays an important role in aging, but it remains unclear regarding the underlying epigenetics and whether this hypothalamic basis can help address aging-related diseases. Here, by comparing mouse hypothalamus with two other limbic system components, we show that the hypothalamus is characterized by distinctively high-level DNA methylation during young age and by the distinct dynamics of DNA methylation and demethylation when approaching middle age. On the other hand, age-related DNA methylation in these limbic system components commonly and sensitively applies to genes in hypothalamic regulatory pathways, notably oxytocin (OXT) and gonadotropin-releasing hormone (GnRH) pathways. Middle age is associated with transcriptional declines of genes which encode OXT, GnRH and signaling components, which similarly occur in an Alzheimer's disease (AD)-like model. Therapeutically, OXT-GnRH combination is substantially more effective than individual peptides in treating AD-like disorders in male 5×FAD model. In conclusion, the hypothalamus is important for modeling age-related DNA methylation and developing hypothalamic strategies to combat AD.
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Registered trials
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