medaura
#336
More on the nitty gritty. Also seems to work on APOE4 carriers. Might also explain part of the neuroprotective effect of SGLT2i drugs, since they put the patient in mild ketosis.
https://www.sciencedirect.com/science/article/pii/S1471489221001582
I have ordered the ketone esters but can’t take them while I nurse as they can be dangerous to the baby.
Also @John_Hemming thought you’d find this interesting:
βOHB improves memory by increasing histone acetylation
βOHB is an inhibitor of endogenous HDACs that lead to the upregulation of genes involved in protection against oxidative stress. βOHB-induced inhibition of HDAC is associated with full transcriptional changes, including those of genes encoding oxidative stress resistance factors FOXO3A and MT2. Treatment of cells with βOHB increased histone acetylation on the FOXO3A and MT2 promoters, both of which were selectively depleted upon HDAC1 and HDAC2activation. Consistent with the increase in FOXO3A and MT2 activity, substantial protection against oxidative stress was observed in mice treated with βOHB [18]. BDNF is a neurotrophic protein with properties that promote neuronal survival and synaptic integrity. Studies in animal models have suggested that BDNFcan inhibit HDAC expression, which leads to the epigenetic downregulation of BDNF by inhibiting the transcription of BDNF promoter I [19]. The overexpression of HDACs increased the amyloid load in AD mice. Inhibiting HDACs can improve spatial memory disorder in mice, suggesting that it could be an effective way of improving the cognitive function of AD patients [20]. Animal studies have shown that βOHB therapy not only improves the acetylation levels of histones H3 and H4 but also antagonizes the reduction of acetylated histones H3 and H4 under low-pressure hypoxia. Moreover, βOHB therapy also promotes PKA/CREB activation and BDNF protein expression. The role of βOHB in improving memory is also due to an increase in the modification of histone acetylation [21]. The tyrosine kinase receptor A (Trk A) signaling pathway is also a key point in protecting cholinergic neurons, which are the most vulnerable in AD. Some animal studies have suggested that βOHB improves TrkA expression by inhibiting HDAC1/3 expression in SH-SY5Y cells; thus, βOHB protects neurons from Aβ-induced neurotoxicity [22].
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Peter attia has zero as a target for his clients, so that is my target
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Interesting. I wonder if that is why Galantamine, which treats dementia may also be used to treat Sarcopenia along with Metformin. Maybe the two diseases are truly linked.
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Pender
#340
I’m around 0.5 lbs visceral fat and 15% body fat. What’s the best way to drop the last 0.5?
I get very hungry if I go below 14% body fat.
I’m doing the things in the videos, etc. in this thread (scroll down) - calorie reduction, exercise, some diet changes: Amount of Central Fat Predicts Mortality Risk in Non-Obese Individuals
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I, too, am trying to lose that last bit of visceral fat. I am trying the GLP-1 inhibiter tirzepatide.
This is my first week of taking it at a low dose of 2.5mg. I have noticed no negative side effects so far, but it will probably take a few months to see any positive results. My current BMI is ~22, and my body fat is ~10-15%. I have been exercising regularly for decades, but getting rid of that last bit of visceral fat has been challenging.
“Multiple studies have shown that tirzepatide can significantly reduce visceral adipose tissue (VAT) in people with type 2 diabetes (T2D):
A study published in Diabetes, Obesity and Metabolism found that tirzepatide treatment resulted in a significant reduction in VAT and liver fat.”
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This is an interesting story, showing just how much we may be able to influence the course of Alzheimers…
Preventive neurologist Dr Richard Isaacson stared at the numbers on the fax in astonishment. Blood biomarkers of telltale signs of early Alzheimer’s disease in the brain of his patient, 55-year-old entrepreneur Simon Nicholls, had all but disappeared in a mere 14 months.
“I had to catch my breath. It was a complete shock: The blood tests on his brain had normalized,” said Isaacson, director of research at the Institute for Neurodegenerative Diseases in Boca Raton, Florida.
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Neo
#345
Yeah, truly is - this case and others are discussed here and in the following posts
Did anyone end up seeing the documentary that they did?
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I did not - but here is more info on it:
Its available on Amazon / Peacock to stream:
https://www.amazon.com/Dr-Sanjay-Gupta-Reports-Alzheimers/dp/B0CVDP5MS5
More details:
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A landmark new statement released by the American Heart Association warns that three common cardiovascular diseases – heart failure, atrial fibrillation and coronary heart disease – raise the risk of developing dementia, an umbrella term describing a set of symptoms including difficulties with memory, thinking, problem-solving, judgement or language.
Research has shown that 14 to 81 per cent of patients with heart failure experience some degree of cognitive impairment. People with atrial fibrillation have a 39 per cent increased risk of memory or thinking problems, while those with heart disease have a 27 per cent higher risk of developing dementia. Following a heart attack, up to 50 per cent of patients experience cognitive decline.
https://www.telegraph.co.uk/health-fitness/conditions/heart-health/heart-conditions-dementia/
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Dr Michael Roizen, chief wellness Officer of Cleveland Clinic on what to do to prevent brain dysfunction.
“Supplements can give you 4 more years of longevity. Stress management can give you 30 years.” -Dr. Roizen
Relacionado:
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Neo
#349
@RapAdmin Do you know if those talks will be online?
No, they won’t be. The above image is from the Longevity Clinics Roundtable at the Buck Institute - and they don’t seem to be recording the talks during the presentations, and don’t have any history of putting anything regarding them online. This is a very focused conference targeted at doctors doing longevity medicine and starting longevity clinics. Its production is a collaboration by the Buck Institute and the Longevity Center EU, and seems designed to accelerate and improve the quality, of longevity clinics globally.
I attended yesterday and did record some of the presentations on my phone, and took photos of the presentations - and will do a write up on what I learned (lots) and put some of the information up here when I have a chance. I was busy today, and didn’t see as much value in today’s agenda, so did not attend.
Earlier last week (Tuesday/Wednesday) were the Longevity Summit conference days, and those were video recorded and will be made available online (mostly, I think). I’m also working on a writeup of that conference.
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adssx
#352
Evidence Mounts for Potential of GLP-1s in Alzheimer’s Disease 2024
While preclinical studies have shown benefits of GLP-1 receptor agonists in targeting the core pathology of Alzheimer’s disease, data from clinical studies are limited, according to an article recently published in the Journal of Alzheimer’s Disease Reports. That’s set to change next year, however, when Novo is expecting readouts from two large Phase III trials, EVOKE and EVOKE Plus, testing semaglutide in patients with Alzheimer’s. Both trials are expected to be completed in September 2025.
“I’m confident that we will see some effects in the Novo Nordisk trials . . . because everything we’ve seen so far supports this concept,” Hölscher told BioSpace. “We know this is a worthwhile target and it definitely should be pursued.”
Meanwhile, Kariya is developing KP405, a first-in-class, dual GLP-1/GIP receptor agonist, initially for Parkinson’s disease with plans for a study in Alzheimer’s. Hölscher previously told BioSpace that drugs like liraglutide and semaglutide have limitations when it comes to treating diseases of the brain. “They’re actually designed to stay in the blood, which is good for diabetes but bad for Alzheimer’s because a drug that stays in the blood doesn’t get into the brain.” The key, therefore, to applying GLP-1s to dementia is getting the drug where it’s needed.
Kariya has removed “add-ons” such as fatty acids that keep GLP-1s in the blood, allowing its drugs to enter the brain at a higher rate, Hölscher explained. The addition of a TAT sequence that is recognized by cell membrane receptors further enable the drug to reach the brain faster, according to Kariya.
Hölscher credited these modifications for helping KP405 to avoid certain side effects linked to GLP-1s in the Phase I Parkinson’s study. “The GLP-1s, the ones designed to treat diabetes, they can cause nausea and stomach upset and all kinds of side effects,” he said. Because KP405 doesn’t stay in the bloodstream, “the peripheral effects are very little.”
As for Novo’s top GLP-1 competitor Eli Lilly, while there are no studies of tirzepatide in Alzheimer’s listed on the ClinicalTrials.gov database, Suvannevejh said it would be a natural fit for a company “whose entire existence is focused on neurology and neuroscience and Alzheimer’s disease.” Lilly’s monoclonal antibody Kisunla was approved in July, becoming the third disease-modifying treatment for the condition and the second actively on the market.
Eli Lilly did not respond to BioSpace‘s request for comment.
Despite the positive signs in certain studies, experts agree that GLP-1s still have a ways to go to prove their worth in Alzheimer’s.
He made a bold prediction regarding Novo’s EVOKE and EVOKE Plus studies: “If those trials show even a small effect, the amyloid strategy will be dead in the water.”
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Agetron
#354
A new take on Alzheimer’s… more might be better?
A recent study published in [Brain]
(https://academic.oup.com/brain/article/147/10/3513/7754406) challenges long-held assumptions about Alzheimer’s disease treatment.
Researchers at the University of Cincinnati found that new monoclonal antibody drugs may slow cognitive decline by increasing levels of a critical brain protein called amyloid-beta 42 (Aβ42), rather than simply reducing amyloid plaques in the brain. This discovery shifts the focus from plaque buildup to the potential role of Aβ42 in maintaining brain health.
Hmmmmm…
@cl-user or other members here… does anyone have access to these Nature articles, and if you do please post the text (or screen captures of the articles):
How fast is your brain ageing? Proteins in blood offer clues
Biomarkers could monitor ageing in the brain, revealing ways to treat dementia and other age-related brain disorders.
https://www.nature.com/articles/d41586-024-04055-0
Plasma proteomics identify biomarkers and undulating changes of brain aging
Proteomics enables the characterization of brain aging biomarkers and discernment of changes during brain aging. We leveraged multimodal brain imaging data from 10,949 healthy adults to estimate brain age gap (BAG), an indicator of brain aging. Proteome-wide association analysis across 4,696 participants of 2,922 proteins identified 13 significantly associated with BAG, implicating stress, regeneration and inflammation. Brevican (BCAN) (β = −0.838, P = 2.63 × 10−10) and growth differentiation factor 15 (β = 0.825, P = 3.48 × 10−11) showed the most significant, and multiple, associations with dementia, stroke and movement functions. Dysregulation of BCAN affected multiple cortical and subcortical structures. Mendelian randomization supported the causal association between BCAN and BAG. We revealed undulating changes in the plasma proteome across brain aging, and profiled brain age-related change peaks at 57, 70 and 78 years, implicating distinct biological pathways during brain aging. Our findings revealed the plasma proteomic landscape of brain aging and pinpointed biomarkers for brain disorders.
https://www.nature.com/articles/s43587-024-00753-6
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