ArticleAging cell2018
Male lifespan extension with 17-α estradiol is linked to a sex-specific metabolomic response modulated by gonadal hormones in mice.
Article in Aging cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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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
51 citing papers in PubMed, 63 citations in OpenAlex.
- Biliopancreatic Diversion Induces Greater Metabolic Improvement Than Roux-en-Y Gastric Bypass.Cell metabolism · 2019Trial
- 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
- Female resistance to the metabolic benefits of protein restriction is reversed by ovariectomy in mice.bioRxiv : the preprint server for biology · 2026Article
- End-of-life pathology in UM-HET3 mice treated with 16 α‑hydroxyestradiol or late‑start canagliflozin.GeroScience · 2026Article
- Remodeling of the Mouse Liver and Skeletal Muscle Metabolome in Response to Continuous Acute Exercise and Disruption of AMPK-Glycogen Interactions.Metabolites · 2026Article
- Article
- Analysis of sex difference in strychnine-intoxicated rat based on the combination of metabolic kinetics and metabolomics.Biology of sex differences · 2025Article
- Sex as a major determinant of pro-longevity drug efficacy: a review of two decades of the NIA Interventions Testing Program.The journals of gerontology. Series A, Biological sciences and medical sciences · 2025Review
- Protection against APOE4-associated phenotypes with the longevity-promoting intervention 17α-estradiol in middle-aged male mice.Communications medicine · 2025Article
- Muscle metabolic resilience and enhanced exercise adaptation by Esr1-induced remodeling of mitochondrial cristae-nucleoid architecture in males.Cell reports. Medicine · 2025Article
- Article
- Sex-dependent adaptations in heart mitochondria from transgenic mice overexpressing cytochrome bMitochondrion · 2025Article
- A pilot study evaluating dosing tolerability of 17α-estradiol in male common marmosets (Callithrix jacchus).GeroScience · 2025Article
- Systemic metabolic benefits of 17α-estradiol are not exclusively mediated by ERα in glutamatergic or GABAergic neurons.GeroScience · 2024Article
- The killifish germline regulates longevity and somatic repair in a sex-specific manner.Nature aging · 2024Article
- Repurposing Drugs for Senotherapeutic Effect: Potential Senomorphic Effects of Female Synthetic Hormones.Cells · 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
- Higher testosterone and testosterone/estradiol ratio in men are associated with decreased Pheno-/GrimAge and DNA-methylation based PAI1.GeroScience · 2024Article
- Responses to Many Anti-Aging Interventions Are Sexually Dimorphic.The world journal of men's health · 2024Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Longevity in mammals is influenced by sex, and lifespan extension in response to anti-aging interventions is often sex-specific, although the mechanisms underlying these sexual dimorphisms are largely unknown. Treatment of mice with 17-α estradiol (17aE2) results in sex-specific lifespan extension, with an increase in median survival in males of 19% and no survival effect in females. Given the links between lifespan extension and metabolism, we performed untargeted metabolomics analysis of liver, skeletal muscle and plasma from male and female mice treated with 17aE2 for eight months. We find that 17aE2 generates distinct sex-specific changes in the metabolomic profile of liver and plasma. In males, 17aE2 treatment raised the abundance of several amino acids in the liver, and this was further associated with elevations in metabolites involved in urea cycling, suggesting altered amino acid metabolism. In females, amino acids and urea cycling metabolites were unaffected by 17aE2. 17aE2 also results in male-specific elevations in a second estrogenic steroid-estriol-3-sulfate-suggesting different metabolism of this drug in males and females. To understand the underlying endocrine causes for these sexual dimorphisms, we castrated males and ovariectomized females prior to 17aE2 treatment, and found that virtually all the male-specific metabolite responses to 17aE2 are inhibited or reduced by male castration. These results suggest novel metabolic pathways linked to male-specific lifespan extension and show that the male-specific metabolomic response to 17aE2 depends on the production of testicular hormones in adult life.
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