Less Soluble Klotho, Greater Inflammation in Osteoarthritis
Klotho is a longevity-associated protein. Studies in mice show that upregulation lengthens life, while downregulation shortens life. In humans, levels of the soluble circulating form of α-klotho correlate with many aspects of aging. More of it is better, less of it is worse. Here, researchers show this to be the case for inflammation related to osteoarthritis. Identification of the full panoply of mechanisms by which klotho acts to improve health remains a work in progress. It is predominantly active in the kidney, and is clearly protective of kidney health and function in later life. Kidney function is important to the rest of the body, and this may be enough to explain much of the effect on health, inflammation, life span, and so forth. Circulating α-klotho appears to have effects on the brain, however, improving cognitive function even in younger animals. It may be that it has meaningful effects on other organs as well.
The systemic immune-inflammation index (SII) is an indicator of neutrophil, lymphocyte, and platelet counts that is used to evaluate inflammation, and it can more objectively reflect changes in the level of inflammation in the body. The SII can be calculated through routine blood examination, which has the advantages of speed, efficiency, simplicity, and low cost. Previous studies have confirmed that the SII has good clinical value in diagnosing chronic diseases such as tumours, osteoporosis, kidney stones, and rheumatoid arthritis.
The Klotho gene (also known as the longevity gene) is related to ageing and is believed to exert antiaging effects through various biological mechanisms. With the increase in academic research on the Klotho gene, the function of the Klotho gene has gradually been elucidated. Previous studies have shown that the Klotho gene plays a key biological role in antioxidant, anti-inflammatory, and antiapoptotic mechanisms; kidney protection; and the improvement of calcium metabolism and phosphorus metabolism.
The association between the SII and serum Klotho has not yet been revealed. To fill this gap, we used data from the National Health and Nutrition Examination Survey (NHANES) database in the United States to explore the relationship between the SII and serum Klotho concentrations in osteoarthritis (OA) patients. This study revealed a significant negative linear relationship between the SII and serum Klotho concentration in OA patients, indicating that a higher SII is associated with lower Klotho concentration. The SII can serve as a predictive indicator of serum Klotho concentrations in OA patients, and Klotho may serve as a potential anti-inflammatory drug for OA treatment. The causal relationship between the SII and serum Klotho concentration still needs further prospective cohort studies or Mendelian randomised studies for verification.
"Several drugs enhance circulating Klotho levels, and some cross the blood-brain barrier to potentially act in the brain. In clinical trials, increased Klotho was noted with renin-angiotensin system inhibitors (losartan, valsartan), a statin (fluvastatin), mTOR inhibitors (rapamycin, everolimus), vitamin D and pentoxifylline. In preclinical work, antidiabetic drugs (metformin, GLP-1-based, GABA, PPAR-γ agonists) also enhanced Klotho. Several traditional medicines and/or nutraceuticals increased Klotho in rodents, including astaxanthin, curcumin, ginseng, ligustilide and resveratrol. Notably, exercise and sport activity increased Klotho."
https://pubmed.ncbi.nlm.nih.gov/35903083/
Strange that I can not find more sources of Klotho or information on human dosing. I suspect it is being filtered out of my search results. The only source I can find, and I only found that indirectly, is buckylabs. And their Klotho is $8 per microgram. Assuming a dose comparable to those used in the monkey study that would be $5,000/dose for a human.
Hah! JohnD, I did the exact same thing when I read this post... I went online and tried to find ways to increase my Klotho levels. Seems to be roughly in line with the diet I currently eat, but I wonder about protein intake.
I would love to get the fightAging.org take on recommended protein intake levels. Blue-zone diets tend to lean more on the lighter protein intake side (.8g per kg of bodyweight). But I've read that increasing to 1 or 1.2g per kg of bodyweight is recommended as you get older. I've also read that protein intake was fairly associated with the signaling for caloric restriction, meaning you could obtain a lot of the CR benefits by simply reducing protein intake down to .8g/kgBW
anyways.... what do you all think? What are your protein intake recommendations? Or does it really matter?
A hugely cheaper approach might be to take sulphoraphane (broccoli), polyphenol ( eg aronia), vitamin D and regular moderate exercise, all of which are known to increase Klotho levels.
The literature mentions resveratrol also, so take pterostilbene instead.
Klotho expression is increased by PPAR-γ activation. " We found that pioglitazone treatment in aging also increased renal klotho expression by more than 60%"
from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2799181/