Document Type : Research Paper I Open Access I Released under CC BY-NC 4.0 license


1 PhD student of exercise physiology, Islamic Azad University , Sari Branch , Iran

2 .Phd, Associate Professor Faculty of Physical Education and Sport Sciences, University of Mazandaran Babolsar, Iran


The aim of this study was to investigate the effect of 6 weeks endurance swimming and vitamin D supplementation on Klotho levels of the brain tissue. In this study, 25 rats were divided into 5 groups: 1) healthy control 2) vehicle 3) vitamin D, 4) swimming and 5) vitamin D + swimming. Swimming training program included one hour daily for 6 weeks and 5 days per week. In addition, supplementary groups were received vitamin D supplement (2ng/0.2mg sesame oil/every other day) intraperitoneally for 2 weeks. Data were analyzed using one-way analysis of variance (ANOVA) and Tukey post hoc test. Klotho levels were measured by ELISA. There was no significant difference in Klotho levels of brain tissue between control and vitamin D groups (p=0/46).The differences between swimming (P=0.03) and vitamin D +swimming (P=0.008) was significant. The results of this study showed that swimming alone and in combination with vitamin D supplementation could increase the Klotho levels of brain tissue and consequently may have neuroprotective role against detrimental factors and leads to a significant increase in resourcesand and finally neuronal protection.


1.   Mallikarjuna K, Shanmugam K, Nishanth K, Wu M-C, Hou C-W, Kuo C-H, et al. Alcohol-induced deterioration in primary antioxidant and glutathione family enzymes reversed by exercise training in the liver of old rats. Alcohol. 2010;44(6):523-9.
2.   Jin J-J, Ko I-G, Kim S-E, Shin M-S, Kim S-H, Jee Y-S. Swimming exercise ameliorates multiple sclerosis-induced impairment of short-term memory by suppressing apoptosis in the hippocampus of rats. Journal of exercise rehabilitation. 2014;10(2):69-74.
3.   NayanataraA, Nagaraja H, Anupama B. The effect of repeated swimming stress on organ weights and lipid peroxidation in rats. Thai J Pharm Sci. 2005;18(1):3-9.
4.   Suleyman H, Gumustekin K, Taysi S, Keles S, Oztasan N, Aktas O, et al. Beneficial effects of Hippophaerhamnoides L. on nicotine induced oxidative stress in rat blood compared with vitamin E. Biological and Pharmaceutical Bulletin. 2002;25(9):1133-6.
5.   Arshadi S, Peeri M, Bakhtiyari S. The effect of 6 weeks swimming training on plasma antioxidants activity in diabetic rats. European Journal of Experimental Biology. 2013;3(5):27-32.
6.   Lopes-Cararo MM, Mazucanti CHY, Scavone C, Kawamoto EM, Berwick DC. The relevance of α-KLOTHO to the central nervous system: Some key questions. Ageing Research Reviews. 2017.
7.   Bektas A, Schurman SH, Sharov AA, Carter MG, Dietz HC, Francomano CA. Klotho gene variation and expression in 20 inbred mouse strains. Mammalian genome. 2004;15(10):759-67.
8.   Maltese G, Karalliedde J. The putative role of the antiageing protein klotho in cardiovascular and renal disease. International journal of hypertension. 2011;2012.
9.   Abraham CR, Chen C, Cuny GD, Glicksman MA, Zeldich E. Small-molecule Klotho enhancers as novel treatment of neurodegeneration. Future. 2012;4(13):1671-9.
10. Duce JA, Podvin S, Hollander W, Kipling D, Rosene DL, Abraham CR. Gene profile analysis implicates Klotho as an important contributor to aging changes in brain white matter of the rhesus monkey. Glia. 2008;56(1):106-17.
11. Kokkinaki M, Abu-Asab M, Gunawardena N, Ahern G, Javidnia M, Young J, et al. Klotho regulates retinal pigment epithelial functions and protects against oxidative stress. The Journal of neuroscience. 2013;33(41):16346-59.
12. Shardell M, Semba RD, Kalyani RR, Hicks GE, Bandinelli S, Ferrucci L. Serum 25-hydroxyvitamin D, plasma klotho, and lower-extremity physical performance among older adults: findings from the InCHIANTI study. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2015:glv017.
13. Imura A, TsujiY, Murata M, Maeda R, Kubota K, Iwano A, et al. α-Klotho as a regulator of calcium homeostasis. Science. 2007;316(5831):1615-8.
14. Sherlin DG, Verma R. Vitamin D ameliorates fluoride-induced embryotoxicity in pregnant rats. Neurotoxicology and teratology. 2001;23(2):197-201.
15. Mitani H, Ishizaka N, Aizawa T, Ohno M, Usui S-i, Suzuki T, et al. In vivo klotho gene transfer ameliorates angiotensin II-induced renal damage. Hypertension. 2002;39(4):838-43.
16. Zeldich E, Chen C-D, Colvin TA, Bove-FendersonEA, Liang J, Zhou TBT, et al. The neuroprotective effect of Klotho is mediated via regulation of members of the redox system. Journal of Biological Chemistry. 2014;289(35):24700-15.
17. Saghiv M, Sherve C, Goldhammer E, Ben-Sira D, Sagiv M. Long LastingChronic Resistive Training Effects on Circulating S-Klotho and IGF-1. Archives of Clinical and Biomedical Research. 2017;1(2):69-75.
18. Schefer V, Talan MI. Oxygen consumption in adult and AGED C57BL/6J mice during acute treadmill exercise of different intensity. Experimental gerontology. 1996;31(3):387-92.
19. Devaraj S, Syed B, Chien A, Jialal I. Validation of an immunoassay for soluble Klotho protein: decreased levels in diabetes and increased levels in chronic kidney disease. American Journal of Clinical Pathology. 2012;137(3):479-85.
20. Ding Y, Li J, Yao W, Rafols J, Clark J, Ding Y. Exercise preconditioning upregulates cerebral integrins and enhances cerebrovascular integrity in ischemic rats. Acta neuropathologica. 2006;112(1):74-84.
21. Goes A, Souza L, Del Fabbro L, De Gomes M, Boeira S, Jesse C. Neuroprotective effects of swimming training in a mouse model of Parkinson’s disease induced by 6-hydroxydopamine. Neuroscience. 2014;256:61-71.
22. Bernardes D, Oliveira-Lima OC, da Silva TV, Faraco CCF, Leite HR, Juliano MA, et al. Differential brain and spinal cord cytokine and BDNF levels in experimental autoimmune encephalomyelitis are modulated by prior and regular exercise. Journal of neuroimmunology. 2013;264(1):24-34.
23. Hanafy KA, Sloane JA. Regulation of remyelination in multiple sclerosis. FEBS letters. 2011;585(23):3821-8.
24. Guardiola‐Diaz HM, Ishii A, Bansal R. Erk1/2 MAPK and mTOR signaling sequentially regulates progression through distinct stages of oligodendrocyte differentiation. Glia. 2012;60(3):476-86.
25. Medici D, Razzaque MS, DeLuca S, Rector TL, Hou B, Kang K, et al. FGF-23–Klotho signaling stimulates proliferation and prevents vitamin D–induced apoptosis. The Journal of cell biology. 2008;182(3):459-65.
26. Fancy SP, Baranzini SE, Zhao C, Yuk D-I, Irvine K-A, Kaing S, et al. Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS. Genes & development. 2009;23(13):1571-85.
27. Yamamoto M, Clark JD, Pastor JV, Gurnani P, Nandi A, Kurosu H, et al. Regulation of oxidative stress by the anti-aging hormone klotho. Journal of Biological Chemistry. 2005;280(45):38029-34.
28. Spach KM, Hayes CE. Vitamin D3 confers protection from autoimmune encephalomyelitis only in female mice. The Journal of Immunology. 2005;175(6):4119-26.
29. Forster RE, Jurutka PW, Hsieh J-C, Haussler CA, Lowmiller CL, Kaneko I, et al. Vitamin D receptor controls expression of the anti-aging klotho gene in mouse and human renal cells. Biochemical and biophysical research communications. 2011;414(3):557-62.
30. Barizzone N, Pauwels I, Luciano B, Franckaert D, Guerini FR, Cosemans L, et al. No evidence for a role of rare CYP27B1 functional variations in multiple sclerosis. Annals of neurology. 2013;73(3):433-7.
31. Kesby JP, Eyles DW, Burne TH, McGrath JJ. The effects of vitamin D on brain development and adult brain function. Molecular and cellular endocrinology. 2011;347(1):121-7.
32. Chang J-M, Kuo M-C, Kuo H-T, Hwang S-J, Tsai J-C, Chen H-C, et al. 1-α, 25-Dihydroxyvitamin D 3 regulates inducible nitric oxide synthase messenger RNA expression and nitric oxide release in macrophage-like RAW 264.7 cells. Journal of Laboratory and Clinical Medicine. 2004;143(1):14-22.