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Klotho deficiency is linked to several diseases and conditions.

Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations


"Klotho deficiency associates with multiple age-related diseases...depressed Klotho levels are linked to hyperphosphatemia, chronic kidney diseases, multiple cardiovascular conditions, neurodegenerative diseases, several types of cancer, pulmonary fibrosis, COPD, bone disease and diabetes (reduced β-cell mass in the pancreas)". https://doi.org/10.3389/fragi.2022.931331 

High Klotho levels promotes increased lifespan.

Klotho is an independent predictor of all-cause mortality. 


  • Klotho concentrations fall with age; people with higher Klotho tend to experience less age‑related disease and longer survival


  • Klotho is associated with protection across cardiovascular, renal, metabolic, and some cancer outcomes


  • High Klotho: have a decreased risk of death during study periods 


  • Low Klotho: reduced lifespan, accelerated aging, increased risk of age related disease, associated with all-cause mortality


Semba, Richard D., Anne R. Cappola, Kai Sun, Stefania Bandinelli, Mansi Dalal, Candace L Crasto, Jack M. Guralnik and Luigi Ferrucci. “Plasma klotho and mortality risk in older community-dwelling adults.” The journals of gerontology. Series A, Biological sciences and medical sciences 66 7 (2011): 794-800 .


Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations  Prud’homme GJ, Kurt M and Wang Q (2022) Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations. Front. Aging 3:931331. https://doi.org/10.3389/fragi.2022.931331 


Kresovich, Jacob K., and Catherine M. Bulka. "Low serum klotho associated with all-cause mortality among a nationally representative sample of American adults." The Journals of Gerontology: Series A 77.3 (2022): 452-456.

 

Cognition & brain health.

  • Individuals with high klotho levels have a lower incidence of stroke and are less likely to develop Alzheimer's disease and dementia.


  • Klotho supports brain health and memory, exerts neuroprotective effects directly by enhancing synaptic function, reducing oxidative damage, and modulating signalling pathways in the brain.


  • Klotho accounted for approximately 3% of the variation in intelligence between individuals, corresponding to a difference of 6 IQ points between those with high and low klotho levels. 


  • In a 2019 study, people with high klotho levels had significantly more brain mass in the areas associated with focus, planning, and working memory (rDLPFC). They also had more neural connections in the area of the brain associated with memory retrieval, thinking ahead, and taking the perspectives of others (rTEMP) 


  • Klotho administration or increased expression enhances synaptic plasticity and cognitive function in aging models. Notably, a study in aged rhesus monkeys showed that a single Klotho treatment improved working memory and spatial cognition for an extended period, supporting translational potential for human cognitive aging



Klotho overexpression protects human cortical neurons from β-amyloid induced neuronal toxicity

Shaker, M.R., Salloum-Asfar, S., Taha, R.Z. et al. Klotho overexpression protects human cortical neurons from β-amyloid induced neuronal toxicity. Mol Brain 18, 27 (2025). https://doi.org/10.1186/s13041-025-01199-6&nbsp


A further summary paper: Klotho: a potential therapeutic target in aging and neurodegeneration beyond chronic kidney disease—a comprehensive review from the ERA CKD-MBD working group 

Mehmet Kanbay, et al. Clinical Kidney Journal, Volume 17, Issue 1, January 2024, sfad276, https://doi.org/10.1093/ckj/sfad276&nbsp


Longevity factor klotho enhances cognition in aged nonhuman primates.

Castner, S.A., Gupta, S., Wang, D. et al. Longevity factor klotho enhances cognition in aged nonhuman primates. Nat Aging 3, 931–937 (2023). https://doi.org/10.1038/s43587-023-00441-x  

Cardiovascular Health.


  • Higher klotho levels are linked to improved endothelial and vascular function, augments nitric oxide signaling (improving circulation), promotes autophagy, reduces inflammation, and protects against heart disease, hypertension, and stroke.


  • Low klotho levels are linked to accelerated atherosclerosis and increased arterial stiffness and vascular calcification.


Klotho Protein and Health and Disease  

https://pubmed.ncbi.nlm.nih.gov/30455427/


Implications of Klotho on Cardiovascular Disease and Health

https://pmc.ncbi.nlm.nih.gov/articles/PMC4278161/


Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations  Prud’homme GJ, Kurt M and Wang Q (2022) Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations. Front. Aging 3:931331. https://doi.org/10.3389/fragi.2022.931331 

 

In Depth Summaries of Klotho

Below are 2 informative blog posts with references to further research on klotho

Wonderous Roots: https://www.wondrousroots.org/klotho 

Live Journal: https://healthtechinfo.livejournal.com/451.html   

Videos on Klotho