Klotho

 

  • Klotho is a blood factor and tumour suppressor across human malignancies (colorectral, gastric, pancreatic, breast, lung, kidney, ovarian, thyroid, melanoma, cervical). (See the 2020 summary paper)

  • Soluble, as well as tissue, Klotho levels progressively reduced in patients with advanced ccRCC. #kidney

  • Klotho suppresses IGF-1-stimulated cell proliferation and migration by inhibiting PI3K/Akt pathway. Klotho acts on IGF-1R signaling functions as tumor suppressor in ccRCC and suggest that Klotho is a potential carcinostatis substance for ccRCC. #kidney

  • Klotho expression blunts RCC cellular migration and invasion in vitro. #kidney

  • Klotho is an antagonist of the Wnt signaling pathway, and chronic Wnt stimulation can lead to stem cell depletion and aging. (wikipedia)

  • Anti-aging effects: Klotho over-expression in mice extended their average life span between 19% and 31% compared to normal mice. In addition, variations in the Klotho gene (SNP Rs9536314) are associated with both life extension and increased cognition in human populations. (wikipedia)

  • Anti-aging: α-klotho can suppress oxidative stress and inflammation, thereby reducing endothelial dysfunction and atherosclerosis. Blood plasma α-klotho is increased by aerobic exercise, thereby reducing endothelial dysfunction. (wikipedia)


Klotho and the Treatment of Human Malignancies, 2020


Klotho suppresses tumor progression via inhibiting PI3K/Akt/GSK3β/Snail signaling in renal cell carcinoma, 2013


Klotho plays a critical role in clear cell renal cell carcinoma progression and clinical outcome, 2016


Soluble Serum αKlotho Is a Potential Predictive Marker of Disease Progression in Clear Cell Renal Cell Carcinoma, 2015


Klotho (wikipedia link)


Klotho is an enzyme that in humans is encoded by the KL gene. There are three subfamilies of klotho: α-klotho, β-klotho, and γ-klotho. α-klotho activates FGF23, and β-klotho activates FGF19 and FGF21. When the subfamily is not specified, the word "klotho" generally means the α-klotho subfamily.


Klotho as a Potential Target

Klotho is a co-factor of fibroblast growth factor 23, which forms a hetero-dimer whose function is to up-regulate the expression of FGF receptors, notably at the site of renal tubules, which increases phosphate expression. Animal models invalidated for Klotho have been described as models of accelerated aging because of the occurrence of early osteoporosis together with extensive vascular calcifications, arteriosclerosis, and genital and skin atrophy [87]. Klotho pathway abnormalities are associated with numerous clinical conditions, and genetic variants of the Klotho gene have been associated with osteoporosis [88]; early coronary artery disease [89]; stroke and vascular dementia [90]; and renal failure [91]. Saito et al. [92] have shown that a rat model with increased risk factors (Otsuka Long Evans Tokushima Fatty) was protected against atherosclerosis and endothelial dysfunction when Klotho was over-expressed. At the present time, we are not aware of any pharmacological compound able to modulate Klotho expression.


Suppression of Aging in Mice by the Hormone Klotho, 2005


A defect in Klotho gene expression in mice accelerates the degeneration of multiple age-sensitive traits. Here, we show that overexpression of Klotho in mice extends life span. Klotho protein functions as a circulating hormone that binds to a cell-surface receptor and represses intracellular signals of insulin and insulin-like growth factor 1 (IGF1), an evolutionarily conserved mechanism for extending life span. Alleviation of aging-like phenotypes in Klotho-deficient mice was observed by perturbing insulin and IGF1 signaling, suggesting that Klotho-mediated inhibition of insulin and IGF1 signaling contributes to its anti-aging properties. Klotho protein may function as an anti-aging hormone in mammals.


Alpha-, Beta-, And Gamma-Klotho's Role In Longevity, Intelligence, Muscle Strength, And Cancer (link)

A great summary of Klotho research (VEGF etc): 


Keith E.

Klotho is amazing. ​​I inject it. Half a trillionth of a gram per day


It has made a huge difference in my strength and workouts, more than Testosterone, growth hormone, gdf11 etc. I must have been deficient or something. it also wakes up your brain, so it acts as a nootropic. Also my skin got super soft and youthful, the effects are all over the place and kind of strange how they are connected. skin, muscles, brain.

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