Peter Attia/ Dr Dena Dubal - Podcast

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Mrjones04
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Peter Attia/ Dr Dena Dubal - Podcast

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Anyone listen to the latest podcast episode of The Drive? Very promising research coming out of UCSF with Dr. Dena Dubal and her research in KLOTHO. Most promising thing I’ve heard lately, though I am new to this! Anyone have any takes on the topic?
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Re: Peter Attia/ Dr Dena Dubal - Podcast

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Mrjones04 wrote: Tue May 28, 2024 1:41 pm Anyone listen to the latest podcast episode of The Drive? Very promising research coming out of UCSF with Dr. Dena Dubal and her research in KLOTHO. Most promising thing I’ve heard lately, though I am new to this! Anyone have any takes on the topic?
Yes, I listened to it. It was posted on the ApoE4.info facebook page this morning. I agree with you, sounds very promising, has the feel of being significant. Although I did note that Peter Attia, whose podcast this interview was conducted on, is an investor in a company working to develop klotho as a therapy for people with Alzheimer’s disease.

For anyone who may be interested, here's the link to the podcast with notes:
#303 – A breakthrough in Alzheimer’s disease: the promising potential of klotho for brain health, cognitive decline, and as a therapeutic tool for Alzheimer’s disease | Dena Dubal, M.D., Ph.D.

Here's the teaser:
Dena Dubal is a physician-scientist and professor of neurology at UCSF whose work focuses on mechanisms of longevity and brain resilience. In this episode, Dena delves into the intricacies of the longevity factor klotho: its formation and distribution in the body, the factors such as stress and exercise that impact its levels, and its profound impact on cognitive function and overall brain health. Dena shares insights from exciting research in animal models showing the potential of klotho in treating neurodegenerative diseases as well as its broader implications for organ health and disease prevention. She concludes with an optimistic outlook for future research in humans and the potential of klotho for the prevention and treatment of Alzheimer’s disease.
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Brian4
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Re: Peter Attia/ Dr Dena Dubal - Podcast

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Dubal has done great work, but I have never heard her address two recent studies (by the way, among the very few on klotho by people without conflicts of interest...) showing the opposite of what Dubal has claimed about the relation between APOE-ε4 status and benefit from higher klotho levels:

https://www.medrxiv.org/content/10.1101 ... 318v1.full
Now published as:
https://pubmed.ncbi.nlm.nih.gov/34219715/

and

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10137709/

Do she and Attia get into these studies in the podcast? If not, that would be a bad sign about their objectivity.

Note, I still think that, on the whole, higher klotho levels are likely good for us 4s. In fact, as I think I mentioned in a different post, I put a team together and we designed and self-tested a plasmid-based α-klotho gene therapy! (We'll be ordering another batch in a month or so.)

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Re: Peter Attia/ Dr Dena Dubal - Podcast

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Their discussion of platelet factor 4 / CXCL4 in enhancing healthy longevity was new (and interesting) to me. The podcast referenced these papers [the times refer to the audio podcast].
Klotho injection induces platelet factors: Platelet factors are induced by longevity factor klotho and enhance cognition in young and aging mice | Nature Aging (C Park et al 2023) | [39:30]

Platelet factors in the blood of young mice rejuvenates the brain of old mice: Platelet factors attenuate inflammation and rescue cognition in ageing | Nature (A Schroer et al 2023) [44:15]

Platelet factor 4 enhances cognition in old mice: Platelet-derived exerkine CXCL4/platelet factor 4 rejuvenates hippocampal neurogenesis and restores cognitive function in aged mice | Nature Communications (O Leiter et al 2023) | [45:15]
In general, I found the podcast interesting, but it seems like there are still a lot of unknowns regarding klotho's mechanism of action, particularly with respect to human dementia.
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Re: Peter Attia/ Dr Dena Dubal - Podcast

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I heard this one today (not finished yet), does anyone know how aspirin might affect the platelet factor production? I’m gonna go down some rabbit holes this is interesting.
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Re: Peter Attia/ Dr Dena Dubal - Podcast

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Aspirin doesn’t but just had a probably useless idea… if the platelets activate along with failing organs close to death due to ischemia and tissue damage, and trigger a huge Klothos spike, could that be a cause for terminal lucidity that is sometimes seen in dying patients? Just in case anyone is interested, this seems to happen in animals too (I’m a veterinarian) as dying animals look better before they then go downhill and die.
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Re: Peter Attia/ Dr Dena Dubal - Podcast

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Veero wrote: Mon Jun 03, 2024 12:06 am Aspirin doesn’t but just had a probably useless idea… if the platelets activate along with failing organs close to death due to ischemia and tissue damage, and trigger a huge Klothos spike, could that be a cause for terminal lucidity that is sometimes seen in dying patients? Just in case anyone is interested, this seems to happen in animals too (I’m a veterinarian) as dying animals look better before they then go downhill and die.
That’s an interesting observation, Veero.
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