The Metabolic, Neuroprotective Cardioprotective And Antitumor Effects Of The Klotho Protein

Mito

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Abstract
Klotho is a transmembrane protein with a wide spectrum of activity. The human Klotho gene shows 86% amino acid identity with the mouse protein. Many important pleiotropic functions of the Klotho protein have been revealed. Amongst them, there is a regulation of nitric oxide production, suppression of oxidative stress and inflammation, influence on the insulin-like growth factors and fibroblast growth factors signaling, modulation of calcium and phosphate metabolism, synthesis of vitamin D and other. Two forms of the Klotho protein are known. The secreted form strongly inhibits the oxidative stress, and, in humans, is more dominant than the membrane form. Studies on a mouse model resulted in the finding of the anti-aging effect of the Klotho protein. This activity is mainly associated with the suppression of oxidative stress, as well as it could be related to neuroprotective, cardioprotective, and metabolic functions.It might be speculated that Klotho, regarded as a neuroprotective factor, may have therapeutical applications in the future in the treatment of demyelinating and neurodegenerative disorders, especially multiple sclerosis (MS) and Alzheimer's disease (AD). The Klotho through inhibition of oxidative stress possesses cardioprotective properties. Of note, one functional variant of Klotho is a risk factor for coronary disease as well as some nucleotide polymorphisms are associated with carotid arteriosclerosis. Moreover, the Klotho protein can inhibit Angiotensin II-induced cardiomyocyte hypertrophy. All those effects indicate that the Klotho protein may be useful in the therapy of heart failure and hypertension. Undoubtedly, metabolic disturbances play an important role in the pathogenesis of many neurodegenerative and cardiovascular diseases. The metabolic effects of the Klotho protein are strongly connected with its neuroprotective and cardioprotective activity. This protein affects adipogenesis, metabolism of glucose and lipids as well as calcium-phosphate system by influence on the activity of fibroblast growth factors (FGF19, FGF23, FGF21). Finally, it has been revealed that the Klotho protein has antitumor activity. Besides, the FGF-Klotho system may have a role in longevity and aging-related disorders.
The metabolic, neuroprotective cardioprotective and antitumor effects of the Klotho protein - PubMed
 

Doludolu

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Abstract
Klotho is a transmembrane protein with a wide spectrum of activity. The human Klotho gene shows 86% amino acid identity with the mouse protein. Many important pleiotropic functions of the Klotho protein have been revealed. Amongst them, there is a regulation of nitric oxide production, suppression of oxidative stress and inflammation, influence on the insulin-like growth factors and fibroblast growth factors signaling, modulation of calcium and phosphate metabolism, synthesis of vitamin D and other. Two forms of the Klotho protein are known. The secreted form strongly inhibits the oxidative stress, and, in humans, is more dominant than the membrane form. Studies on a mouse model resulted in the finding of the anti-aging effect of the Klotho protein. This activity is mainly associated with the suppression of oxidative stress, as well as it could be related to neuroprotective, cardioprotective, and metabolic functions.It might be speculated that Klotho, regarded as a neuroprotective factor, may have therapeutical applications in the future in the treatment of demyelinating and neurodegenerative disorders, especially multiple sclerosis (MS) and Alzheimer's disease (AD). The Klotho through inhibition of oxidative stress possesses cardioprotective properties. Of note, one functional variant of Klotho is a risk factor for coronary disease as well as some nucleotide polymorphisms are associated with carotid arteriosclerosis. Moreover, the Klotho protein can inhibit Angiotensin II-induced cardiomyocyte hypertrophy. All those effects indicate that the Klotho protein may be useful in the therapy of heart failure and hypertension. Undoubtedly, metabolic disturbances play an important role in the pathogenesis of many neurodegenerative and cardiovascular diseases. The metabolic effects of the Klotho protein are strongly connected with its neuroprotective and cardioprotective activity. This protein affects adipogenesis, metabolism of glucose and lipids as well as calcium-phosphate system by influence on the activity of fibroblast growth factors (FGF19, FGF23, FGF21). Finally, it has been revealed that the Klotho protein has antitumor activity. Besides, the FGF-Klotho system may have a role in longevity and aging-related disorders.
The metabolic, neuroprotective cardioprotective and antitumor effects of the Klotho protein - PubMed
Very interesting. Have the researchers mentioned any ways (or you found yourself) to upregulate Klotho protein systems?
 

Mauritio

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Very interesting. Have the researchers mentioned any ways (or you found yourself) to upregulate Klotho protein systems?
Klotho is a very fascinating molecule!
Haidut posted studies about policosanol boosting klotho, I think androgens per se also boost klotho ,but policosanol from vitamin E , certain rum , or just as a supplement does for sure .
 

Doludolu

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Klotho is a very fascinating molecule!
Haidut posted studies about policosanol boosting klotho, I think androgens per se also boost klotho ,but policosanol from vitamin E , certain rum , or just as a supplement does for sure .
thank you. androgens you mean perhaps boost the klotho protein expression? Will look into policosanol. Rum - well that's interesting haha
thank you, brother !
 
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Mito

Mito

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Abstract
During the evolution of skeletons, vertebrates acquired the bone made of calcium phosphate. By keeping the extracellular fluid in a supersaturated condition regarding calcium and phosphate, vertebrates create the bone when and where they want simply by providing a cue for precipitation. To secure this strategy, a new endocrine system has evolved that strictly controls the extracellular phosphate concentration. In response to phosphate intake, fibroblast growth factor-23 (FGF23) is secreted from the bone and acts on the kidney through binding to its receptor Klotho to increase urinary phosphate excretion and maintain phosphate homeostasis. The FGF23-Klotho endocrine system, when disrupted, results in hyperphosphatemia and ectopic precipitation of calcium phosphate in mice and humans. In addition to disturbed phosphate homeostasis, mice lacking Klotho suffer from premature aging. They exhibit multiple organ atrophy, arteriosclerosis characterized by vascular calcification, cardiac hypertrophy, sarcopenia, cognition impairment, frailty, and a shortened life span associated with chronic non-infectious inflammation. Restoration of the phosphate balance by placing Klotho- or FGF23-deficient mice on low phosphate diet rescued them from the aging-like phenotypes, indicating that phosphate was responsible for the accelerated aging. The similar pathophysiology is universally observed in patients with chronic kidney disease (CKD), rendering advanced CKD a clinical model of accelerated aging. CKD patients bear colloidal nanoparticles containing calcium phosphate in the blood, which are termed calciprotein particles (CPPs). CPPs have the ability to induce cell damage and inflammation, potentially contributing to accelerated aging. Terrestrial vertebrates with the bone made of calcium phosphate may be destined to age due to ectopic calcium phosphate.


 
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Mito

Mito

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Triiodothyronine (T3) enhances lifespan and protects against oxidative stress via activation of Klotho in Caenorhabditis elegans​

Abstract​

Age predisposes individuals to significant diseases, and the biological processes contributing to aging are currently under intense investigation. Klotho is an anti-aging protein with multifaceted roles and is an essential component of the endocrine fibroblast growth factor. In Caenorhabditis elegans (C. elegans), there are two prospective orthologs of α-Klotho, C50F7.10, and E02H9.5, identified. The two orthologs' products are homologous to the highly conserved KL1 domain of human and mouse Klotho protein. Considering the endocrine system's major involvement in an organism's homeostasis and that thyroid disorders increase with advancing age, the molecular mechanisms underlying its impact on different endocrine components during the aging process remain poorly characterized. In this study, we sought to determine the regulatory role of Triiodothyronine (T3) on homologs genes of klotho and its impact on different parameters of aging in the C. elegans model organism. We showed that T3 could increase the mRNA expressions of the klotho homologous genes in C. elegans. Moreover, T3 could also extend a worm lifespan and modulate oxidative stress resistance and aging biomarkers significantly and positively. Further investigations employing different mutant and transgenic strains reveal that these observed effects are mediated through the EGL-17/EGL-15 pathway via Klotho activation along with the involvement of transcription factor DAF-16. In conclusion, these findings have revealed an unexpected link between T3 and Klotho and how this link can modulate the aging process in C. elegans via activation of klotho. This study will help understand the crosstalk and regulations of different endocrine components and their consequences on the aging process in multiple species.

 

Mauritio

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Klotho is an interesting Protein!

 

Mauritio

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