Dementia: Klotho Injection Improves Cognition in Monkey 

Researchers have found that memory in aged monkey improved following a single administration of low-dose Klotho protein. It is the first time that restoring levels of klotho has been shown to improve cognition in a non-human primate. This paves the way for clinical trials in future to test if klotho treatment may prove therapeutic in aging humans with dementia due to Alzheimer disease (AD).  

Klotho is a naturally occurring protein. It is mainly produced in the kidney and exists in three forms. Membrane Klotho is involved in aging and the development of chronic diseases. The secreted Klotho acts as humoral factor and in organ protection while intracellular form of Klotho protein supresses cellular senescence. It is called Longevity factor because of its anti-aging biological functions.  

The circulating levels of Klotho protein deceases with the age. A study on animal in 2015 had demonstrated that mice with reduced Klotho level had accelerated aging while increased levels of Klotho enhanced lifespan¹. Similar results were found in another study reported in the same year on human amyloid precursor protein (hAPP) transgenic mice – increasing Klotho protein expression reduced premature mortality and neural network dysfunctions². These animal experiments suggested that Klotho protein level plays a key role in aging which is very important risk factor for the most common neurodegenerative disorder called Alzheimer disease (AD).  

Association of Klotho with Alzheimer disease (AD) came to the fore courtesy a cross-sectional observational study reported last year. The study involved 243 patients with Alzheimer disease (AD) and cognitively healthy controls. It was found that Klotho levels in Cerebro-spinal fluid (CSF) were significantly higher among healthy controls. The individuals with dementia due to Alzheimer disease had lower Klotho CSF levels. Further, Klotho levels differed in clinical stages of Alzheimer disease³.  

Could restoring Klotho levels in individuals with dementia due to Alzheimer disease be an approach to treat and prevent such disorders? This may be possible only after clinical trials are conducted and safety and efficacy results are found to be satisfactory. But a milestone towards this has been reached for a non-human primate.  

In a study⁴ reported on 03 July 2023, the researchers found that memory in aged monkey was enhanced following a single administration of low-dose Klotho protein. It is the first time that restoring levels of klotho has been shown to improve cognition in a non-human primate. This paves the way for clinical trials to test if klotho treatment may prove therapeutic in aging humans. 

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References: 

1. Kim J. et al 2015. Biological Role of Anti-aging Protein Klotho. Journal of Lifestyle Medicine 2015; 5:1-6. Published online March 31, 2015; DOI: https://doi.org/10.15280/jlm.2015.5.1.1 

2. Dubal D.B. et al. 2015. Life Extension Factor Klotho Prevents Mortality and Enhances Cognition in hAPP Transgenic Mice. Journal of Neuroscience 11 February 2015, 35 (6) 2358-2371; DOI: https://doi.org/10.1523/JNEUROSCI.5791-12.2015 

3. Grøntvedt G.R. et al 2022. Association of Klotho Protein Levels and KL-VS Heterozygosity With Alzheimer Disease and Amyloid and Tau Burden. JAMA Netw  Open. 2022;5(11):e2243232. DOI: https://doi.org/10.1001/jamanetworkopen.2022.43232 

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

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