ArticleNeurobiology of aging2019
Neuroendocrine aging precedes perimenopause and is regulated by DNA methylation.
Article in Neurobiology of aging, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Genetic Variation and Hot Flashes: A Systematic Review.The Journal of clinical endocrinology and metabolism · 2020Pooled it
- Blood proteomics of menopause map to brain aging and dementia risk.Nature medicine · 2026Article
- Plasma proteomics link menopause timing to brain aging and dementia risk.Research square · 2026Article
- Plasma proteomics link menopause timing to brain aging and dementia risk.medRxiv : the preprint server for health sciences · 2026Article
- APOE4 Accelerates Menopause-Associated Brain Metabolic Shift and Disrupts Bioenergetic Adaptation.bioRxiv : the preprint server for biology · 2026Article
- APOE4 accelerates menopause-associated brain metabolic shift and disrupts bioenergetic adaptation.Frontiers in aging neuroscience · 2026Article
- Epigenomic alterations in psychiatric disorders and glioblastoma.Epigenomics · 2026Review
- Multifaceted dynamics of circadian timing system influence aging and longevity.Biogerontology · 2025Review
- Impact of the natural female reproductive aging on the rat serum lipidome.Clinical science (London, England : 1979) · 2025Article
- Progesterone-induced activation of progesterone receptor alleviates alveolar bone resorption and inflammatory response in periodontitis.Clinical oral investigations · 2025Article
- Accelerated midlife endocrine and bioenergetic brain aging in APOE4 females.Frontiers in aging neuroscience · 2025Article
- Therapeutic effects and mechanism analysis of Paeonia lactiflora extract (PLE) in menopausal rats with hot flashes.Frontiers in pharmacology · 2025Article
- The effect of stellate ganglion block on postoperative recovery quality in peri-menopausal women undergoing gynecological laparoscopic surgery.Frontiers in medicine · 2025Article
- Editorial: Genetics and epigenetics in ovarian aging.Frontiers in endocrinology · 2025Article
- Progesterone affects periodontitis in perimenopausal women and in an experimental rat model.Journal of dental sciences · 2025Article
- Epigenetic developmental mechanisms underlying sex differences in cancer.The Journal of clinical investigation · 2024Review
- The Heterogeneity of Post-Menopausal Disease Risk: Could the Basis for Why Only Subsets of Females Are Affected Be Due to a Reversible Epigenetic Modification System Associated with Puberty, Menstrual Cycles, Pregnancy and Lactation, and, Ultimately, Menopause?International journal of molecular sciences · 2024Review
- Melatonin Induces Analgesic Effects through MTResearch (Washington, D.C.) · 2024Article
- Mitochondria: the epigenetic regulators of ovarian aging and longevity.Frontiers in endocrinology · 2024Review
- Exploring the causal association between epigenetic clocks and menopause age: insights from a bidirectional Mendelian randomization study.Frontiers in endocrinology · 2024Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Perimenopause marks initiation of female reproductive senescence. Age of onset is only 47% heritable suggesting that additional factors other than inheritance regulate this endocrine aging transition. To elucidate these factors, we characterized transcriptional and epigenomic changes across endocrine aging using a rat model that recapitulates characteristics of the human perimenopause. RNA-seq analysis revealed that hypothalamic aging precedes onset of perimenopause. In the hypothalamus, global DNA methylation declined with both age and reproductive senescence. Genome-wide epigentic analysis revealed changes in DNA methylation in genes required for hormone signaling, glutamate signaling, and melatonin and circadian pathways. Specific epignetic changes in these signaling pathways provide insight into the origin of perimenopause-associated neurological symptoms such as insomnia. Treatment with 5-aza-2'-deoxycytidine, a DNA-methyltransferase-1 inhibitor, accelerated transition to reproductive senescence/ whereas supplementation with methionine, a S-adenosylmethionine precursor, delayed onset of perimenopause and endocrine aging. Collectively, these data provide evidence for a critical period of female neuroendocrine aging in brain that precedes ovarian failure and that DNA methylation regulates the transition duration of perimenopause to menopause.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.