ArticleThe journals of gerontology. Series A, Biological sciences and medical sciences2022
17-α-Estradiol Has Sex-Specific Effects on Neuroinflammation That Are Partly Reversed by Gonadectomy.
Article in The journals of gerontology. Series A, Biological sciences and medical sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
24 citing papers in PubMed, 26 citations in OpenAlex.
- VCD-induced estropause fails to enhance responsiveness to 17α-estradiol in adult female mice.GeroScience · 2026Article
- 17α-Estradiol: A mildly feminizing estrogen with sex-specific metabolic and lifespan benefits.Ageing research reviews · 2026Review
- The relationships between diabetic male infertility, diabetic cognitive impairment, and the neuroendocrine-immune network: A review.Medicine · 2026Review
- Canagliflozin Reprograms the Aging Hippocampus in Genetically Diverse UM-HET3 Mice and Attenuates Alzheimer's-Like Pathology.Aging cell · 2025Article
- Strategies for studying sex differences in brain aging.Trends in genetics : TIG · 2025Review
- Protection against APOE4-associated phenotypes with the longevity-promoting intervention 17α-estradiol in middle-aged male mice.Communications medicine · 2025Article
- Characterization of craniofacial tissue aging in genetically diverse HET3 male mice with longevity treatment of 17-alpha estradiol.Archives of oral biology · 2025Article
- A pilot study evaluating dosing tolerability of 17α-estradiol in male common marmosets (Callithrix jacchus).GeroScience · 2025Article
- The estrogen-brain interface in neuroinflammation: a multidimensional mechanistic insight.Frontiers in aging neuroscience · 2025Review
- Systemic metabolic benefits of 17α-estradiol are not exclusively mediated by ERα in glutamatergic or GABAergic neurons.GeroScience · 2024Article
- Hypothalamic MRI-derived microstructure is associated with neurocognitive aging in humans.Neurobiology of aging · 2024Article
- 17α-Estradiol alleviates high-fat diet-induced inflammatory and metabolic dysfunction in skeletal muscle of male and female mice.American journal of physiology. Endocrinology and metabolism · 2024Article
- Responses to Many Anti-Aging Interventions Are Sexually Dimorphic.The world journal of men's health · 2024Review
- 17α-estradiol does not adversely affect sperm parameters or fertility in male mice: implications for reproduction-longevity trade-offs.GeroScience · 2023Article
- Assessing tolerability and physiological responses to 17α-estradiol administration in male rhesus macaques.GeroScience · 2023Article
- Lifespan-extending interventions induce consistent patterns of fatty acid oxidation in mouse livers.Communications biology · 2023Article
- Metabolic benefits of 17α-estradiol in liver are partially mediated by ERβ in male mice.Scientific reports · 2023Article
- A Genetically Heterogeneous Rat Model with Divergent Mitochondrial Genomes.The journals of gerontology. Series A, Biological sciences and medical sciences · 2023Article
- Chromosomal and gonadal factors regulate microglial sex effects in the aging brain.Brain research bulletin · 2023Review
- Metabolic benefits of 17α-estradiol in liver are partially mediated by ERβ in male mice.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
17-α-Estradiol (17aE2) treatment from 4 months of age extends life span in male mice and can reduce neuroinflammatory responses in the hypothalamus of 12-month-old males. Although 17aE2 improves longevity in males, female mice are unaffected, suggesting a sexually dimorphic pattern of life-span regulation. We tested whether the sex-specific effects of 17aE2 on neuroinflammatory responses are affected by gonadal removal and whether hypothalamic changes extend to other brain regions in old age. We show that sex-specific effects of 17aE2 on age-associated gliosis are brain region specific and are partially dependent on gonadectomy. 17aE2 treatment started at 4 months of age protected 25-month-old males from hypothalamic inflammation. Castration before 17aE2 exposure reduced the effect of 17aE2 on hypothalamic astrogliosis in males. In contrast, sex-specific inhibition of microgliosis generated by 17aE2 was not significantly affected by castration. In the hippocampus, gonadectomy influenced the severity of gliosis and the responsiveness to 17aE2 in a region-dependent manner. The male-specific effects of 17aE2 correlate with increases in hypothalamic estrogen receptor alpha expression, specifically in gonadally intact males, consistent with the idea that 17aE2 might act through this receptor. Our results indicate that neuroinflammatory responses to 17aE2 are partially controlled by the presence of sex-specific gonads. Loss of gonadal function and age-associated neuroinflammation could, therefore, influence late-life health and disease onset, leading to sexual dimorphism in both aging and in response to drugs that modify the pace of aging.
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Registered trials
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