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Agingdoc⭐David Barzilai🔔MD PhD MS MBA DipABLM🩺 Profile picture
@agingdoc1
Sep 23, 2020 • 3 tweets • 2 min read • Read on X
#BHB inhibits #inflammasome activation to attenuate #Alzheimer’s disease #pathology | Journal of #Neuroinflammation |

“Here, we find BHB levels are lower in red blood cells and brain parenchyma of AD patients when compared with non-AD controls... jneuroinflammation.biomedcentral.com/articles/10.11…
...Furthermore, exogenous BHB administration reduced plaque formation, microgliosis, apoptosis-associated speck-like protein containing a caspase recruitment domain (Asc) speck formation, and caspase-1 activation in the 5XFAD mouse model of AD.”
“Taken together, our findings demonstrate that BHB reduces AD pathology by inhibiting NLRP3 inflammasome activation. Additionally, our data suggest dietary or pharmacological approaches to increase BHB levels as promising therapeutic strategies”

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More from @agingdoc1

Agingdoc⭐David Barzilai🔔MD PhD MS MBA DipABLM🩺 Profile picture
Jan 21, 2023
SkepDoc's Corner: Deuterium Depleted Water

By @HHSkepDoc

skepticalinquirer.org/exclusive/deut…
Sample of recent publication (which promoted my lit search and identifying Harriet's blog post👆 -@agingdoc1):

Deuterium Content of the Organic Compounds in Food Has an Impact on Tumor Growth in Mice

mdpi.com/1467-3045/45/1… (@CIMB_MDPI)
1st author Gábor Somlyai interview:

[posted by @DominicDAgosti2: ]

Compare with @TuftsUniversity @TuftsNutrition @NutritionLetter

Q. Does the amount of deuterium in drinking water matter to one’s health?👇

nutritionletter.tufts.edu/ask-experts/q-…
Read 4 tweets
Agingdoc⭐David Barzilai🔔MD PhD MS MBA DipABLM🩺 Profile picture
Jan 21, 2023
I asked chat-GPT to help me write a tweet thread on how it can help accelerate progress in geroscience. Here’s what she came up with… 👇

/1
"Exciting news! #ChatGPT is being used to accelerate progress in the field of #geroscience. The ability to understand and generate human-like text allows for efficient data analysis and novel research opportunities. #AI #HealthTech

/2
"Did you know that #ChatGPT can assist scientists in the field of #geroscience with tasks such as data analysis and literature review? This technology has the potential to speed up discoveries and developments in the fight against age-related diseases. #AI #HealthTech

/3
Read 7 tweets
Agingdoc⭐David Barzilai🔔MD PhD MS MBA DipABLM🩺 Profile picture
Sep 29, 2020
Rapamycin dosing hypothesis:

This is just a hypothesis, needs testing: Severe mTORC2 inhibition is harmful (esp in males), but mild inhibition is ~neutral or possibly mildly beneficial in some settings (eg-cancer). This is a thread, keep clicking on msg to keep reading....
Advise 1st read in full includ. intro & discus. re: mTORC2 inhibition concerns (1) ncbi.nlm.nih.gov/pmc/articles/P… & (2) onlinelibrary.wiley.com/doi/full/10.11… (3) pubmed.ncbi.nlm.nih.gov/31577953/ (4) pubmed.ncbi.nlm.nih.gov/31373126/ (5) pubmed.ncbi.nlm.nih.gov/32720643/ (6) pubmed.ncbi.nlm.nih.gov/30794726/
@LammingLab & other great work
Problems w/ excess mTORC2 inhibition was mostly shown under:

1)Genetic⬇️eg, full/partial KO
2) Strong NON-rapamycin inhibition, eg RNA interference
3) non-WT or genetic eg murine models
4) HFD or kcal overfeeding
5) High rapa dosing➡️⬆️lipids,insulin,gluc, or other lab issues
Read 38 tweets
Agingdoc⭐David Barzilai🔔MD PhD MS MBA DipABLM🩺 Profile picture
Sep 27, 2020
@Blagosklonny The following is for educational purposes only, and not medical advice.
@Blagosklonny is a pioneer in rapamycin research & was the first to propose it has the potential to extend life based on its mechanism of action (keep reading, this discussion & calculations are stacked)..🧑‍🔬 Image
@Blagosklonny his prediction was subsequently confirmed in Saccharomyces (yeast), C elegans (nematode worms), Drosophila (fruit flies), mice, and others.
Rapamycin (sirolimus) has been used off-label for theorized healthspan and/or lifespan by such celebrities as @PeterAttiaMD...(keep reading)
@Blagosklonny @PeterAttiaMD You can see Dr. Blagosklonny practices what he preaches: 10 mg/week: bit.ly/349jlpM. The discussion that follows puts this in some respects very modest dose in perspective and provides a framework for thinking about dosing (more or less– in the 10-30+mg rapamycin range).
Read 45 tweets
Agingdoc⭐David Barzilai🔔MD PhD MS MBA DipABLM🩺 Profile picture
Sep 25, 2020
Science is tricky: “Of the four main signaling pathways implied to be linked to the impact of CR on lifespan ([IIS, NF-ĸB, mTOR & sirtuins])...the pathways except SIRT were altered in a manner consistent with increased lifespan.” (Cont.).... ncbi.nlm.nih.gov/pmc/articles/P…
...so to what extent does this reflect 1) role of sirtuins in CR (2)(-) extrapolation from C57BL/6 mice 3) assay sensitivity 4) experiment conditions 5) network complexity 6) “other”. This was a great study & trends>individual studies. Every💪 study ➡️ ⬆️ Q’s than A’s, to explore
Also “In our graded CR study, expression levels of mTORC1 and mTORC2 were both strongly negatively associated with the increase in CR.” Recall the latter is one concern for regular rapamycin (⬆️glucose,⬆️lipids.... but not always and not in case of CR)....
Read 6 tweets
Agingdoc⭐David Barzilai🔔MD PhD MS MBA DipABLM🩺 Profile picture
Sep 24, 2020
“The aging organism may also be viewed as a system with chemical fluctuations caused by biological reactions in the organism. This notion takes the whole organism as collected microscopically ordered patterns resembling oscillating chemical reactions.”

5 👍for correct author ID!
“In such reactions, the chemicals involved form a dissipative structure far from the equilibrium, which allowed the raw materials to be transformed to maintain as a certain self‐assembled biological structure that is ordered both spatially and temporally.....
However, it is harder to maintain such structures when the biological organization of an organism is constrained by its own biology and the genome evolution needed to maximize fitness, and is further impacted by age‐related changes...”
Read 6 tweets

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