ArticlePloS one2024
Aerobic exercise up-regulates Klotho to improve renal fibrosis associated with aging and its mechanism.
Article in PloS one, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Multi-omics profiling reveals systemic rejuvenation of the aged kidney through senolytic therapy.NPJ Regenerative medicine · 2026Article
- Rehabilitation for Cardiorenal Multimorbidity: Epidemiology, Functional Phenotypes, and Effects on Physical Function, Renal Trajectory, and Prognosis.Journal of clinical medicine · 2026Review
- The preventive effects of exercise on renal dysfunction in D-galactose treated rats: the role of miR-296-5p and SGLT2.European journal of applied physiology · 2026Article
- Exercise and tissue fibrosis: recent advances in therapeutic potential and molecular mechanisms.Frontiers in endocrinology · 2025Review
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Authors and funding
5 authors.
Funding
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Abstract
Renal fibrosis is a major cause of renal dysfunction and is a common pathological event in almost all forms of chronic kidney disease (CKD). Currently, the pathomechanisms of renal fibrosis are not well understood. However, researchers have demonstrated that aerobic exercise can improve renal fibrosis. Klotho is considered to be a negative regulator of renal fibrosis. In this study, we aimed to investigate the role and mechanism of Klotho in the improvement of renal fibrosis through aerobic exercise. We performed a 12-week aerobic exercise intervention in 19-month-old male C57BL/6J mice. Physiological and biochemical indexes were performed to assess renal function and renal fibrosis. The roles of Klotho were further confirmed through knockdown of Klotho by small interfering RNA (siRNA) in C57BL/6J mice.Q-PCR and Western blot were performed to quantify determine the expression of relevant genes and proteins in the kidney. Results: Aging decreased Klotho expression via activated the upstream TGF-β1/p53/miR34a signaling pathway and affected its downstream signaling pathways, ultimately leading to renal fibrosis. Exposure to aerobic exercise for 12 weeks significantly improved renal fibrosis and alleviated the intrarenal genetic alterations induced by aging. Conclusion: Our results showed that aerobic exercise increased Klotho expression by inhibiting the TGF-β1/p53/miR34a signaling pathway and further inhibited its downstream TGF-β1/smad3 and β-linker protein signaling pathways. These results provide a theoretical basis supporting the feasibility of exercise in the prevention and treatment of CKD.
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