ArticleFrontiers in endocrinology2023
Involvement of p38 MAPK in Leydig cell aging and age-related decline in testosterone.
Article in Frontiers in endocrinology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Pooled it
- Testicular ageing as a central hallmark of male senescence: characteristics, molecular mechanisms and emerging therapeutic strategies.Annals of medicine · 2026Review
- Estradiol mitigates lipid accumulation, oxidative stress, apoptosis, and MAPKs activation in NASH rat model with bilateral orchidectomy.PNAS nexus · 2026Article
- Lycopene Alleviates T-2 Toxin-Induced Testosterone Synthesis Disorder by Inhibiting ROS/p38/TORC2/CREB Axis.Antioxidants (Basel, Switzerland) · 2026Article
- The 24/7 lifestyle and male hormonal health: how sleep deprivation and ultra-processed foods impact testosterone and reproduction.Reviews in endocrine & metabolic disorders · 2026Review
- Dietary patterns and testosterone balance: a review of clinical data and perspectives.Journal of advanced research · 2026Review
- Single-cell analysis of fetal testis reveals dysfunction of human Leydig cells in Klinefelter syndrome.The Journal of clinical investigation · 2026Article
- Male testosterone synthesis disorders: oxidative stress pathways, regulatory mechanisms, potential of antioxidant therapy, and botanical medicine prospects.Asian journal of andrology · 2026Review
- Review
- METTL3 regulates Leydig cell proliferation via miR-145-PCK1 mediated gluconeogenesis in goats.Journal of animal science and biotechnology · 2026Article
- The EV-mitochondrial outsourcing network as a therapeutic target for age-related testosterone deficiency: from network collapse to clinical intervention.Frontiers in endocrinology · 2026Review
- PINK1 overexpression suppresses p38 MAPK/NF‑κB signaling to attenuate chondrocyte senescence in osteoarthritis.International journal of molecular medicine · 2025Article
- The effects of testicular aging on Leydig cells and the application of stem cells in restoring Leydig cells function.Reproductive biology and endocrinology : RB&E · 2025Review
- Effects of Aging on Mammalian Spermatogenesis From a Cellular Perspective.Molecular reproduction and development · 2025Review
- Prepubertal Diabetes Stagnates Testicular Development by Skewing Autophagy Homeostasis in Leydig Cells.Cells · 2025Article
- Mechanisms of Leydig Cell Aging and Obesity-Related Hypogonadism in Men: A Review.Medical science monitor : international medical journal of experimental and clinical research · 2025Review
- The Role of Environmental Endocrine Disruptors on Leydig Cell Death and Senescen.The world journal of men's health · 2025Review
- Review
- Exploring the Mechanisms of Testicular Aging: Advances in Biomarker Research.Aging and disease · 2025Review
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Introduction: Age-related decline in testosterone is associated with Leydig cell aging with impaired testosterone synthesis in aging. Obesity accelerates the age-related decline in testosterone. However, the mechanisms underlying the Leydig cell aging and the effects of obesity on Leydig cell aging remain unclear. Method: Natural aging mice and diet-induced obese mice were used to assess the process of testicular Leydig cell senescence with age or obesity. Bioinformatic analysis of the young and aged human testes was used to explore key genes related Leydig cell aging. Leydig cell-specific p38 MAPK knockout (p38LCKO) mice were used to further analyze the roles of p38 MAPK in Leydig cell aging. The levels of testosterone and steroidogenic enzymes, activity of p38 MAPK, aging status of Leydig cells, and oxidative stress and inflammation of testes or Leydig cells were detected by ELISA, immunoblotting, immunofluorescence, and senescence-associated β-galactosidase (SA-β-Gal) staining analysis, respectively. Result: The serum testosterone level was significantly reduced in aged mice compared with young mice. In the testis of aged mice, the reduced mRNA and protein levels of LHCGR, SRB1, StAR, CYP11A1, and CYP17A1 and the elevated oxidative stress and inflammation were observed. KEGG analysis showed that MAPK pathway was changed in aged Leydig cells, and immunoblotting displayed that p38 MAPK was activated in aged Leydig cells. The intensity of SA-β-Gal staining on Leydig cells and the number of p21-postive Leydig cells in aged mice were more than those of young mice. Similar to aged mice, the testosterone-related indexes decreased, and the age-related indexes increased in the testicular Leydig cells of high fat diet (HFD) mice. Aged p38LCKO mice had higher levels of testosterone and steroidogenic enzymes than those of age-matched wild-type (WT) littermates, with reduced the intensity of SA-β-Gal staining and the expression of p21 protein. Conclusion: Our study suggested that obesity was an important risk factor for Leydig cell aging. p38 MAPK was involved in Leydig cell aging induced by age and obesity. The inhibition of p38 MAPK could delay Leydig cell aging and alleviate decline in testosterone.
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