ArticlePloS one2012
Testosterone deficiency accelerates neuronal and vascular aging of SAMP8 mice: protective role of eNOS and SIRT1.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 83 citations in OpenAlex.
- Cognitive effects of testosterone and finasteride administration in older hypogonadal men.Clinical interventions in aging · 2014Trial
- Ginsenoside Rb1 attenuates age-associated cognitive impairment by modulating oxidative stress and the SIRT1/eNOS/NO axis.Journal of ginseng research · 2025Article
- Hormonal and Sex-Specific Regulation of Key Players in Fibro-Calcific Aortic Valve Disease.International journal of molecular sciences · 2025Article
- Sex-specific behavioral changes in middle-aged mice.Scientific reports · 2025Article
- Enhanced Acute Muscle Activation in ALS Patients Following Liposomal Curcumin, Resveratrol, and Dutasteride Administration.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Female sex is linked to a stronger association between sTREM2 and CSF p-tau in Alzheimer's disease.EMBO molecular medicine · 2025Article
- Unveiling the molecular and cellular links between obstructive sleep apnea-hypopnea syndrome and vascular aging.Chinese medical journal · 2025Review
- Local synthesis and function of neuro-estrogen and neuro-androgen: impact on the hippocampus-related cognition and neuronal plasticity.Frontiers in cellular neuroscience · 2025Review
- Melatonin attenuates scopolamine-induced cognitive dysfunction through SIRT1/IRE1α/XBP1 pathway.CNS neuroscience & therapeutics · 2024Article
- Advanced Progress of Histone Deacetylases in Rheumatic Diseases.Journal of inflammation research · 2024Review
- Causal effects of serum testosterone levels on brain volume: a sex-stratified Mendelian randomization study.Journal of endocrinological investigation · 2023Article
- Secreted Cytokines within the Urine of AKI Patients Modulate TP53 and SIRT1 Levels in a Human Podocyte Cell Model.International journal of molecular sciences · 2023Article
- Is Dutasteride a Therapeutic Alternative for Amyotrophic Lateral Sclerosis?Biomedicines · 2022Review
- [Testosterone and Alzheimer's disease].Problemy endokrinologii · 2022Article
- Induction of Accelerated Aging in a Mouse Model.Cells · 2022Review
- Impact of Testosterone on Alzheimer's Disease.The world journal of men's health · 2022Review
- Alzheimer's Amyloid-β Accelerates Human Neuronal Cell Senescence Which Could Be Rescued by Sirtuin-1 and Aspirin.Frontiers in cellular neuroscience · 2022Article
- Androgen Therapy in Neurodegenerative Diseases.Journal of the Endocrine Society · 2020Review
- Androgens' effects on cerebrovascular function in health and disease.Biology of sex differences · 2020Review
- Sex differences in Alzheimer's-related Tau biomarkers and a mediating effect of testosterone.Biology of sex differences · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxidative stress and atherosclerosis-related vascular disorders are risk factors for cognitive decline with aging. In a small clinical study in men, testosterone improved cognitive function; however, it is unknown how testosterone ameliorates the pathogenesis of cognitive decline with aging. Here, we investigated whether the cognitive decline in senescence-accelerated mouse prone 8 (SAMP8), which exhibits cognitive impairment and hypogonadism, could be reversed by testosterone, and the mechanism by which testosterone inhibits cognitive decline. We found that treatment with testosterone ameliorated cognitive function and inhibited senescence of hippocampal vascular endothelial cells of SAMP8. Notably, SAMP8 showed enhancement of oxidative stress in the hippocampus. We observed that an NAD(+)-dependent deacetylase, SIRT1, played an important role in the protective effect of testosterone against oxidative stress-induced endothelial senescence. Testosterone increased eNOS activity and subsequently induced SIRT1 expression. SIRT1 inhibited endothelial senescence via up-regulation of eNOS. Finally, we showed, using co-culture system, that senescent endothelial cells promoted neuronal senescence through humoral factors. Our results suggest a critical role of testosterone and SIRT1 in the prevention of vascular and neuronal aging.
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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.