Dena Dubal: Longevity Factor Klotho, Cognition, Brain Aging, and Alzheimer’s Disease

BRAIN PONDERINGS podcast with Mark Mattson

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In 1997 Makoto Kuro-o and his colleagues reported that they had accidentally discovered a gene that encodes a protein that slows aging and extends the lifespan of mice. They named the protein ‘Klotho’ after the Greek goddess that ‘spins the thread of life’. During the past decade University of California San Francisco professor Dena Dubal has shown that Klotho can enhance learning and memory and protect neurons and synapses aging dysfunction and degeneration in mouse models of Alzheimer’s disease. Klotho production is increased by exercise and intermittent fasting. In this episode Dr. Dubal talks about her research on Klotho and the potential of Klotho as a treatment for cognitive impairment, Alzheimer’s disease, and other brain disorders..
LINKS:
Review article on Klotho:
file:///Users/markmattson/Downloads/s41581-018-0078-3%20(1).pdf
Klotho enhances cognition in old nonhuman primates:
www.ncbi.nlm.nih.gov/pmc/arti...
Klotho treatment in a mouse model of Alzheimer’s disease:
www.ncbi.nlm.nih.gov/pmc/arti...
Klotho treatment in a mouse model of Parkinson’s disease:
www.ncbi.nlm.nih.gov/pmc/arti...
Intermittent fasting and Klotho:
www.ncbi.nlm.nih.gov/pmc/arti...
Neuronal activity and Klotho:
www.ncbi.nlm.nih.gov/pmc/arti...

Опубликовано:

12 мар 2024

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Комментарии : 8

@eugeniebreida1583 4 месяца назад

Excellent guest, once again, Mark! Wowzer, exciting work is afoot out there. So inspiring to hear from the brains behind the scenes, your interviews are quite a gift.

@peterz53 Месяц назад

2nd listen - BTW the Interment Fasting Klotho study was done in lab of Sandrine Thuret (French) and published in 2021 in Molecular Psychiatry "Intermittent fasting enhances long-term memory consolidation adult hippocampal neurogenesis, and expression of longevity gene Klotho" Open access. Every other day fasting in mice. Would like to know about TRE in humans.

@peterz53 4 месяца назад

Thanks. FYI, the Conboy lab also showed increased platelet factor 4 (PF4) in lab animals undergoing plasma exchange, simply removing about 50% of old plasma which altered expression of many genes (see their 2020 and 2022 studies) Did not see that they evaluated Klotho expression changes or made the connection to Klotho. As an aside, in the US you can donate plasma at the blood banks where whole blood is donated. Plasma volume removed is about 25% if doing plasma only, so may have a positive effect if one is older and it is repeated monthly for a while. As a 69 yo male I've been daily exercising for 12 years and doing daily time restricted eating for about 8 years. Monthly plasma donations for 2 years. The exercise and dietary habits (good food quality and TRE) have probably made a huge cumulate difference given my age.

@Mark-hu5hq 4 месяца назад

Thanks for your comments. The plasma donation is interesting. It seems likely that removing plasma induces an adaptive stress response(s) and PF4 is part of the stress response.

@bennguyen1313 Месяц назад

Regarding how the kidneys produce Klotho, yet it doesn't cross the Blood-Brain-Barrier.. aside from Platelet-Factor-4 what other pathway is thought to be mediating the neuron helmet? Would love to see a urine/blood test to measure klotho activity by the kidneys.. for brain and early CKD detection.

@krisvette5874 4 месяца назад

Fascinating interview. Incredible findings on the Klotho protein. I will follow the Dubai Lab now. Great podcast series.

@eugeniebreida1583 4 месяца назад

Dena Dubal glows with both genius and goodwill - I am sure I’m hardly alone in wishing her godspeed that her current ‘baby’ Klothos gets into practical use on behalf of the real masses of suffering humans who are in need. (Saddened to hear she is not connected with getting these hormonal (?) proteins to market.