Applications of Klotho Protein

Diseases of Aging

Natural human Klotho is associated with improved cognitive performance in humans. In fact, 25% of the population naturally produces higher levels of Klotho. In these people, executive thinking is measurably better and parts of the brain measurably bigger than the normal population. That is, an 85 year old who has higher levels of Klotho has similar brain size and thinking ability to someone over 10 years younger1. Lifespan is affected too. In animal studies, overexpression of Klotho leads to 20-30% longer lives2 than those with normal Klotho levels.

1. Yokoyama JS et al., (Jan 2015).“Variation in longevity gene klotho is associated with greater cortical volumes”. Annals Clin. Trans. Neurology.

2. Kurosu H et al., (Sep 2005). “Suppression of aging in mice by the hormone Klotho”. Science.

Kidney Disease

Klotho plays a major role in kidney disease as much of the Klotho protein circulating in the blood is produced in the kidneys. Klotho levels are known to decline in chronic kidney disease (CKD) and may be an early marker of this disease1. Klotho deficiency may be one of the causes for CKD progression and resulting complications including cardiovascular disease. Klotho has also been shown to play a role in acute kidney injury. In animal studies, Klotho reduced the size of the kidney injury and promoted healing2.

1. Nehra JA and Hu MC., (Apr 2017). “Potential application of klotho in human chronic kidney disease”. Bone.

2. Hu MC, et al., (Sept 2010). “Klotho deficiency is an early biomarker of renal ischemia-reperfusion injury and its replacement is protective”. Kidney Int.


Klotho also plays a role in cancer, a disease that kills more than 500,000 Americans every year. Several studies show that Klotho levels are decreased in certain types of human tumor cells/tissues and reduced Klotho expression in liver cancer patients was associated with decreased survival1. In addition, multiple animal studies have shown that Klotho can improve survival rates2, reduce metastasis and reduce cancer cell resistance to chemotherapeutic agents3.

1. Tang, X., et al., ( Feb 2016). “ Klotho: a tumor suppressor and modulator of the Wnt/β-catenin pathway in human hepatocellular carcinoma”. Laboratory Investigation; a Journal of Technical Methods and Pathology

2. Ligumsky, H., et al., (Oct 2015). “Tumor Suppressor Activity of Klotho in Breast Cancer Is Revealed by Structure–Function Analysis”. Molecular Cancer Research

3. Wang, Y., et al., (Feb 2013). “Klotho Sensitizes Human Lung Cancer Cell Line to Cisplatin via PI3k/Akt Pathway”. PLOS One.


Klotho levels are associated with insulin production in human and animal studies. The Centers for Disease Control indicate that >29 million Americans are living with diabetes1, and 86 million are living with prediabetes, which significantly increases their risk of type 2 diabetes and other chronic diseases. Human and animal research2 show that Klotho levels are decreased in the pancreatic islets in diabetics and lack of Klotho is associated with decreased insulin production. When diabetic mice were treated with Klotho for 2 weeks, blood glucose levels declined significantly, accompanied by significant increases in insulin levels3.

1. CDC, (2016):

2. Lin y and Sun Z., (Apr 2015). “In Vivo Pancreatic β-Cell–Specific Expression of Antiaging Gene Klotho: A Novel Approach for Preserving β-Cells in Type 2 Diabetes”. Diabetes

3. Forsberg, E.A., et al., (Mar 2016). “Effect of systemically increasing human full-length Klotho on glucose metabolism in db/db mice”. Diabetes Research and Clinical Practice