Unique Neuroprotective Effect of Klotho and How to Increase it Naturally

Physionic

Dec 23, 2024

Episode description

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0:00 - Introduction
0:57 - Klotho's Genetic Neuroprotective Effect
3:33 - Klotho's Long-term Neuroprotective Effect
5:00 - Klotho's direct Neuroprotective Effect
6:10 - Fascinating Mechanism of Action
9:18 - Klotho Therapies?
9:35 - Improving Klotho Naturally

References
[Study 371] Ananya FN, Ahammed MR, Lahori S, et al. Neuroprotective Role of Klotho on Dementia. Cureus. 2023;15(6):e40043. Published 2023 Jun 6. doi:10.7759/cureus.40043

Funding/Conflicts: No Funding / No Conflicts of Interest

[Study 372] Zhao Y, Zeng CY, Li XH, Yang TT, Kuang X, Du JR. Klotho overexpression improves amyloid-β clearance and cognition in the APP/PS1 mouse model of Alzheimer's disease. Aging Cell. Published online September 21, 2020. doi:10.1111/acel.13239

Funding/Conflicts: Public Funding [National Natural Science Foundation of China] / No Potential Conflicts of Interest

[Study 373] Erickson CM, Schultz SA, Oh JM, et al. KLOTHO heterozygosity attenuates APOE4-related amyloid burden in preclinical AD. Neurology. 2019;92(16):e1878-e1889. doi:10.1212/WNL.0000000000007323

Funding/Conflicts: Public Funding [National Institute of Aging / National Institute of Neurological Disorders] / Potential Conflicts of Interest [Some researchers are consultants for Industry - Alzheon, BioArctic, Biogen, Eli Lilly, etc.]

[Study 374] Dubal DB, Yokoyama JS. Longevity Gene KLOTHO and Alzheimer Disease-A Better Fate for Individuals Who Carry APOE ε4. JAMA Neurol. 2020;77(7):798-800. doi:10.1001/jamaneurol.2020.0112

Funding/Conflicts: Unknown Funding / Potential Conflicts of Interest [Researchers have consulted for Industry - Unity BioTech]

[Study 375] Castner SA, Gupta S, Wang D, et al. Longevity factor klotho enhances cognition in aged nonhuman primates. Nat Aging. 2023;3(8):931-937. doi:10.1038/s43587-023-00441-x

Funding/Conflicts: Mixed Funding [National Institute of Health / Bradley, Godsoe and Bakar Families / Unity BioTech] / Potential Conflicts of Interest [Some researchers consulted for Unity BioTech, SV Health Investors, and are founders of KL therapeutics]

[Study 376] Park C, Hahn O, Gupta S, et al. Platelet factors are induced by longevity factor klotho and enhance cognition in young and aging mice. Nat Aging. 2023;3(9):1067-1078. doi:10.1038/s43587-023-00468-0

Funding/Conflicts: Mixed Funding [National Institute of Health / National Center for Advanced Translational Sciences / Bradley, Godsoe and Bakar Families] / Potential Conflicts of Interest [Some of the researchers are looking to patent this work]

[Study 377] Corrêa HL, Raab ATO, Araújo TM, et al. A systematic review and meta-analysis demonstrating Klotho as an emerging exerkine. Sci Rep. 2022;12(1):17587. Published 2022 Oct 20. doi:10.1038/s41598-022-22123-1

[Study 378] Belloy ME, Napolioni V, Han SS, Le Guen Y, Greicius MD; Alzheimer’s Disease Neuroimaging Initiative. Association of Klotho-VS Heterozygosity With Risk of Alzheimer Disease in Individuals Who Carry APOE4. JAMA Neurol. 2020;77(7):849-862. doi:10.1001/jamaneurol.2020.0414

Funding/Conflicts: Mixed Funding [National Institute of Health / Iqbal Farrukh and Asad Jamal Center of Cognitive Health in Aging] / No Potential Conflicts of Interest

[Study 379] Kuro-o M, Matsumura Y, Aizawa H, et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature. 1997;390(6655):45-51. doi:10.1038/36285

Funding/Conflicts: Public [Core Research for Evolutional Science & Technology] / Unknown Conflicts

[Study 380] Dubal DB, Yokoyama JS, Zhu L, et al. Life extension factor klotho enhances cognition. Cell Rep. 2014;7(4):1065-1076. doi:10.1016/j.celrep.2014.03.076

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Mindsip insights from this episode:

Prioritize resistance training to maximize Clotho levels

While both endurance and resistance exercise raise Clotho, current evidence suggests resistance training has a more robust effect on increasing its levels.

#Clotho

#exercise

Boost Clotho protein levels through resistance training

Exercise, particularly resistance training, has been shown to be a natural and effective way to increase the body's levels of the Clotho protein.

#Clotho

#exercise

Leverage Clotho protein to guard against APOE4 dementia

The Clotho protein offers protection against dementia, including the devastating APOE4 version of Alzheimer's disease.

#APOE4

#Clotho

Leverage Clotho gene mutation to reduce cognitive impairment risk

A specific mutation in the Clotho gene leads to higher expression of the protein and is associated with a substantial reduction in cognitive impairment risk.

#Clotho

#genetics

Understand Clotho's limitations in crossing blood-brain barrier

Despite its brain-protective effects, the Clotho protein itself does not cross the blood-brain barrier when administered into the body.

#brain

#Clotho

Activate clotho to enhance cognitive benefits through PF4

Clotho activates platelets in the blood to release Platelet Factor 4 (PF4), a molecule that does cross the blood-brain barrier to deliver cognitive benefits.