Aerobic exercise‑stimulated Klotho upregulation extends life span by attenuating the excess production of reactive oxygen species in the brain and kidney

Ji, Naichun; Luan, Jing; Hu, Fu-Gang; Zhao, Yirong; Lv, Bosen; Wang, Wen; Xia, Meng; Zhao, Xuebo; Lao, Kejing

doi:10.3892/etm.2018.6597

Cited by 31 publications

(26 citation statements)

References 40 publications

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“…Oxidative damage to the brain caused by excessive reactive oxygen species has been implicated in the psychopathology of cognitive impairments in schizophrenia (Wang et al, 2018;Xie et al, 2019). Klotho protein has an ability to protect organ against oxidative stress damage (Nagai et al, 2003;Ji et al, 2018;Zhou et al, 2018). Perhaps, accumulated reactive oxygen species might stimulate the body to produce more klotho protein to alleviate the oxidative damage.…”

Section: Discussionmentioning

confidence: 99%

Increased Plasma Level of Longevity Protein Klotho as a Potential Indicator of Cognitive Function Preservation in Patients With Schizophrenia

et al. 2020

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Cognitive impairments are a core feature of schizophrenia. Klotho is an anti-aging protein with demonstrated cognitive-enhancing effects on the brain. The purpose of this study was to investigate the differences in levels of plasma klotho between patients with schizophrenia and healthy controls, as well as the relationship between klotho level and cognitive function in patients. Forty patients with schizophrenia and 40 gender-and age-matched healthy individuals were recruited. Positive and Negative Syndrome Scale (PANSS) was used to assess the psychopathology of patients. A neuropsychological battery was performed to evaluate the cognitive function of participants. Plasma klotho was measured using enzyme-linked immunosorbent assay. We show that patients with schizophrenia performed worse in the neurocognitive tests than the healthy controls. The levels of plasma klotho were significantly higher in schizophrenia patients than in healthy controls (p < 0.001). In patients, plasma klotho levels were positively correlated with cognitive function with regard to attention (p = 0.010), working memory (p < 0.001), verbal memory (p = 0.044), executive function (p < 0.001), and composite cognitive score (p < 0.001). Stepwise linear regression analysis shows that executive function had the highest correlation with plasma klotho levels (β = 0.896, t = 8.290, p < 0.001). Collectively, these results indicate that anti-aging protein klotho may be implicated in the pathogenesis of schizophrenia, and increased klotho may act as a compensatory factor for the preservation of cognitive function in schizophrenia. Further studies are needed to investigate the dynamic changes of klotho and the mechanisms by which klotho modulates cognition in schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Increased Plasma Level of Longevity Protein Klotho as a Potential Indicator of Cognitive Function Preservation in Patients With Schizophrenia

et al. 2020

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“…The expression of α-klotho is regulated by many factors. Exercise (both acute and chronic) was reported to affect the expression of α-klotho in the brain and kidneys (Ji et al, 2018), as well as the level of soluble α-klotho in the serum (Matsubara et al, 2014;Santos-Dias et al, 2016;Dalise et al, 2017;Amaro-Gahete et al, 2019). But the physiological mechanism is unclear.…”

Section: Discussionmentioning

confidence: 99%

α-Klotho Expression in Mouse Tissues Following Acute Exhaustive Exercise

Rao

Zheng

et al. 2019

Front. Physiol.

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α-Klotho, a multifunctional protein, has been demonstrated to protect tissues from injury via anti-oxidation and anti-inflammatory effects. The expression of α-klotho is regulated by several physiological and pathological factors, including acute inflammatory stress, oxidative stress, hypertension, and chronic renal failure. Exhaustive exercise has been reported to result in tissue damage, which is induced by inflammation, oxidative stress, and energy metabolism disturbance. However, little is known about the effects of exhaustive exercise on the expression of α-klotho in various tissues. To determine the effects, the treadmill exhaustion test in mice was performed and the mice were sacrificed at different time points following exhaustive exercise. Our results confirmed that the full-length (130 kDa) and shorter-form (65 kDa) α-klotho were primarily expressed in the kidneys. Moreover, we found that, except for the kidneys and brain, other tissues primarily expressed the shorter-form α-klotho, including liver, which was in contrast to previous reports. Furthermore, the shorter-form α-klotho was decreased immediately following the acute exhaustive exercise and was then restored to the pre-exercise level or even higher levels in the next few days. Our results indicate that α-klotho may play a key role in the body exhaustion and recovery following exhaustive exercise.

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“…The running speed was constant and set at 30 cm/s. The training protocol was based on previous experimental studies [26][27][28][29]. The animals that did not exercise throughout the entire study period were used as sedentary controls.…”

Section: Experimental Design and Treatmentmentioning

confidence: 99%

The effects of long-term moderate exercise and Western-type diet on oxidative/nitrosative stress, serum lipids and cytokines in female Sprague Dawley rats

et al. 2021

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Purpose Regular exercise reduces obesity and the risk of cardiovascular disease. However, health-promoting benefits of physical activity are commonly associated with increased inflammation and oxidative stress. Here, we tested whether constant moderate exercise is able to prevent or attenuate the oxidative/nitrosative stress, inflammation, and serum lipids in lean and obese rats. Methods Four-month-old female Sprague Dawley rats received standard or a high-fat diet. Animals were subjected to a physical activity protocol, consisting of 30 min forced treadmill exercise for 5 consecutive days per week during 10 months. Baseline and sedentary (non-exercised) rats were used as controls. Lipids, oxidized low-density lipoprotein cholesterol, nitric oxide metabolites, and pro- and anti-inflammatory markers were measured in blood collected upon euthanasia. Results At variance to young baseline control rats, 14-month-old animals fed normal diet had increased plasma lipid levels, including total cholesterol and triglycerides, which were further elevated in rats that consumed a high-fat diet. While treadmill exercise did not lower the amount of serum lipids in standard diet group, forced physical activity reduced non-high-density lipoprotein cholesterol in response to high-fat diet feeding. Exercised rats fed standard diet or high-fat diet had lower abundancy of nitric oxide metabolites, which coincided with increased levels of oxidized low-density lipoprotein cholesterol. Accordingly, the amount of nitric oxide metabolites correlated inversely with oxidized low-density lipoprotein cholesterol and homo-arginine. Exercise significantly reduced inflammatory cytokines in high-fat diet fed rats only. Conclusion Our study suggests that regular exercise alters the equilibrium between oxidative and anti-oxidative compounds and reduces pro-inflammatory cytokines.

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Aerobic exercise‑stimulated Klotho upregulation extends life span by attenuating the excess production of reactive oxygen species in the brain and kidney

Cited by 31 publications

References 40 publications

Increased Plasma Level of Longevity Protein Klotho as a Potential Indicator of Cognitive Function Preservation in Patients With Schizophrenia

Increased Plasma Level of Longevity Protein Klotho as a Potential Indicator of Cognitive Function Preservation in Patients With Schizophrenia

α-Klotho Expression in Mouse Tissues Following Acute Exhaustive Exercise

The effects of long-term moderate exercise and Western-type diet on oxidative/nitrosative stress, serum lipids and cytokines in female Sprague Dawley rats

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