Interesting bit about COX. COX-1 protects our stomach lining while COX-2 can be targeted to down-regulate inflammation. This is why over the counter pain medication that down-regulates inflammation can be hard on the stomach. Red Cherries (not Rainier cherries) also target COX-2, and are more preferential to COX-2 over COX-1 than these pain medications. I guess this doesn't directly relate to your topic, but it is an interesting tangent. Edit: It looks like Ginger is even more selective of COX-2 over COX-1.
This reminds me of work done to understand inflammation pathways. it's interesting that aspirin works at low doses by acetylating cyclooxygenase COX1, inhibiting platelet generation of thromboxane A2, thus reducing blood clots. At high doses it acts on both COX1 and COX2 blocking prostaglandin production, reducing pain, fever, and inflammation. It also inhibits SIRT1 and AMPK to induce senescence. I can't help but wonder what other roles aspirin might have on sirtuin pathways? Could it be a longevity drug?
Curious if this is relevant to Parkinson's as well. I was diagnosed in 2019 at the age of 50, and I'm trying to understand the inner cell workings. A lot of new stuff to learn, but extremely interesting. I've recently become particularly interested in aging processes, as they seem to have a lot in common with Parkinson's. Not only concerning mitochondria health and autophagy/mitophagy, but also senescence. A study from 2019 suggests that dopamine producing cells don't just die, but instead enter a state of senescence. Parkinson's looks to me in many ways like local, early aging in certain parts of the brain.
The dopaminergic neurons are more moribund than senescent in the manner of 'senescent cells' in this context. Neurons don't divide, and cellular senescence applies to cells that undergo division. PD is, however, typically an age-related disease and therapies against aging will likely prevent and possibly even treat PD (most cases, there are some cases of young onset PD). There's a forum on HealthUnlocked called 'Cure Parkinson's' you might like. There's also The Science of Parkinson's blog by Simon Stott. I have a blog that is more of an open notebook you can find by searching "rhyobrain" on DuckDuckGo. My father had MSA.
I think you're saying that senescent cells hoard dihomo-15d-PGJ2, perhaps as part of cell defense strategy. And by hoard I mean amass and do not secrete. I think you're then saying that since this is the case, irrespective of why it's the case, the levels of dihomo-15d-PGJ2 in body fluids is only notably elevated whenever dihomo-15d-PGJ2 is released upon the effective dismantling (death) of senescent cells, from which we can therefore gauge the efficacy of senolytics. I hope that's what you are saying, and that it's true, and that similar biomarkers can be identified. It seems this would be of especial value if it turns out different kinds of senescent cells (harmful ones versus beneficial ones) turn out to hoard uniquely identifiable molecules. That way senolytics can be developed, (one should hope), which can be shown to target what's harmful while leaving what's beneficial intact.
Not sure how I missed this release, but this video was great! I can't wait until I see more Patreons added to the list. You're really onto something with this channel. Any thoughts on a Discord Server or Slack channel? Would love to have a small community to discuss your videos.
To what extent does fasting eliminate senescent cells? I recall reading somewhere that when we fast the volume of our internal organs shrinks because the body is eliminating defective cells not just defective proteins (autophagy). These are then replaced by new cells upon refeeding. Is this correct? If so it would make fasting the poor person's senolytic. Might also explain some of the anti-aging effects of fasting.
Came upon an interesting topic - clonal hematopoiesis of indeterminate potential (CHIP); there's a 2019 open access review article in J Am Coll Cardiology by Libby et al.
Very interesting. Why would dihomo-15d-PGJ2 be released though? If the senescent cell has an "orderly" apoptotic death, shouldn't it be contained in vesicles and eaten by macrophages? Also, if dihomo-15d-PGJ2 is released, could it then be taken up by other cells and accelerate their progression to senescence?
Both really good questions! First one especially, i am not entirely sure how their method enables detection and it could be different senolytics differ in how they trigger apoptosis/cell death outcome which could confound using just dihomo-15d-pgj2 as a biomarker
@@TheSheekeyScienceShow Gotcha, sorry for the misunderstanding. That seems in harmony with the ITP findings (while appreciating any substance can be operating through a variety of mechanisms when it comes to longevity).
Love your videos, but your pronunciation of ‘efficacy’ (used in lots of vids) is now irritating (sorry I’m one of those). It’s pronounced EFF-A-KA-SEE [update: EFF-ER-KA-SEE is perfect].
Perhaps we should just say effectiveness as English is a global language so we need to make it as simple as possible. The medical profession is getting as bad as the legal profession with their legalese.
@@hcholm pretty close, but I’d say it’s exactly like “Eff-er-ka-see”, but I hadn’t thought of using two letters. With one letter, both ‘E’ and ‘A’ are a bit of a kludge, but I still think ‘A’ is closer although it’s moot now.
dihomo-15d-PGJ2!! :D
quite an understatement that it's still a bit of a mouthful hahahah
Expelliarmus!!!!!!!!!#%!#$%@!!!!@@!@!@!!!!!!!!!
Interesting bit about COX. COX-1 protects our stomach lining while COX-2 can be targeted to down-regulate inflammation. This is why over the counter pain medication that down-regulates inflammation can be hard on the stomach. Red Cherries (not Rainier cherries) also target COX-2, and are more preferential to COX-2 over COX-1 than these pain medications.
I guess this doesn't directly relate to your topic, but it is an interesting tangent.
Edit: It looks like Ginger is even more selective of COX-2 over COX-1.
Sounds poetic 🙂
And I'm glad to find your channel
A tip: you can watch series on Flixzone. Me and my gf have been using it for watching a lot of movies lately.
You are becoming my favorite channel.
Glad you got some sponsorship and don't have to rely on willpower alone to keep making these vids!
Thanks for your efforts; your videos are enjoyable, well-done, informative, and most importantly, current. Oh, and I LOVE your accent!
Thank you for another highly informative video. You are a blessing to mankind! God bless.
Yours are always good but this one was BRILLIANT! Thanks for all your hard work in putting it together…well done.
Great video! I like the research updates that you produce. :-)
This reminds me of work done to understand inflammation pathways. it's interesting that aspirin works at low doses by acetylating cyclooxygenase COX1, inhibiting platelet generation of thromboxane A2, thus reducing blood clots. At high doses it acts on both COX1 and COX2 blocking prostaglandin production, reducing pain, fever, and inflammation. It also inhibits SIRT1 and AMPK to induce senescence. I can't help but wonder what other roles aspirin might have on sirtuin pathways? Could it be a longevity drug?
What a wonderful channel!! 👍
Really great video and exciting progress in senescence!
Brilliant video as usual. Thanks!
Curious if this is relevant to Parkinson's as well. I was diagnosed in 2019 at the age of 50, and I'm trying to understand the inner cell workings. A lot of new stuff to learn, but extremely interesting. I've recently become particularly interested in aging processes, as they seem to have a lot in common with Parkinson's. Not only concerning mitochondria health and autophagy/mitophagy, but also senescence. A study from 2019 suggests that dopamine producing cells don't just die, but instead enter a state of senescence. Parkinson's looks to me in many ways like local, early aging in certain parts of the brain.
The dopaminergic neurons are more moribund than senescent in the manner of 'senescent cells' in this context. Neurons don't divide, and cellular senescence applies to cells that undergo division. PD is, however, typically an age-related disease and therapies against aging will likely prevent and possibly even treat PD (most cases, there are some cases of young onset PD).
There's a forum on HealthUnlocked called 'Cure Parkinson's' you might like. There's also The Science of Parkinson's blog by Simon Stott. I have a blog that is more of an open notebook you can find by searching "rhyobrain" on DuckDuckGo. My father had MSA.
@@rhyothemisprinceps1617 I'm following The Science of Parkinson's, will check out HealthUnlocked and your blog.
I think you're saying that senescent cells hoard dihomo-15d-PGJ2, perhaps as part of cell defense strategy. And by hoard I mean amass and do not secrete. I think you're then saying that since this is the case, irrespective of why it's the case, the levels of dihomo-15d-PGJ2 in body fluids is only notably elevated whenever dihomo-15d-PGJ2 is released upon the effective dismantling (death) of senescent cells, from which we can therefore gauge the efficacy of senolytics. I hope that's what you are saying, and that it's true, and that similar biomarkers can be identified. It seems this would be of especial value if it turns out different kinds of senescent cells (harmful ones versus beneficial ones) turn out to hoard uniquely identifiable molecules. That way senolytics can be developed, (one should hope), which can be shown to target what's harmful while leaving what's beneficial intact.
Not sure how I missed this release, but this video was great! I can't wait until I see more Patreons added to the list. You're really onto something with this channel. Any thoughts on a Discord Server or Slack channel? Would love to have a small community to discuss your videos.
thx but wow.....my head is spinning !! so how far are we in terms of human trails ?
Glorious.
Excellent presentation. Thanks.
Great content... What are your thoughts around fasting, use of NAD+ precursors and hyperbaric chamber therapy?
Thanks and i have videos on all of these aleeady
To what extent does fasting eliminate senescent cells? I recall reading somewhere that when we fast the volume of our internal organs shrinks because the body is eliminating defective cells not just defective proteins (autophagy). These are then replaced by new cells upon refeeding. Is this correct? If so it would make fasting the poor person's senolytic. Might also explain some of the anti-aging effects of fasting.
To a big extend, that is why every espécie on the planet get to live longer if they fast regularly
Came upon an interesting topic - clonal hematopoiesis of indeterminate potential (CHIP); there's a 2019 open access review article in J Am Coll Cardiology by Libby et al.
Very interesting. Why would dihomo-15d-PGJ2 be released though? If the senescent cell has an "orderly" apoptotic death, shouldn't it be contained in vesicles and eaten by macrophages?
Also, if dihomo-15d-PGJ2 is released, could it then be taken up by other cells and accelerate their progression to senescence?
Both really good questions! First one especially, i am not entirely sure how their method enables detection and it could be different senolytics differ in how they trigger apoptosis/cell death outcome which could confound using just dihomo-15d-pgj2 as a biomarker
so...bottomline...what do I ingest to clear senescent cells??
Fisetin
Foxo4-dri perhaps, although it's an experimental product.
Azithromycin
senescent cells increase ace2 receptors for Cov 19
th-cam.com/video/k3f8KQbhujc/w-d-xo.html&ab_channel=Frontiers
Better sound today!
Fasting or exercite claro them
dihomo-15d-PGJ2
In simple English what is it all about.???
Slightly confused. The downregulating effect of aspirin on COX2 might then increase senescent cells? (Seems at odds with the ITP findings )
So, cox2 activity seems to drives senescence (here, by increasing dihomo-15d-pgj2),so inhibiting by aspirin would in theory reduce it
@@TheSheekeyScienceShow so...take aspirin to clear senescent cells??
@@TheSheekeyScienceShow Gotcha, sorry for the misunderstanding. That seems in harmony with the ITP findings (while appreciating any substance can be operating through a variety of mechanisms when it comes to longevity).
@@Splassshhh1234 Research Fisetin [not medical advice]
@@Splassshhh1234 Taking a low-dose slow-release aspirin might be also beneficial against advanced glycation end products (AGEs).
Can we not just say PGJ2 for short? :D
Love your videos, but your pronunciation of ‘efficacy’ (used in lots of vids) is now irritating (sorry I’m one of those). It’s pronounced EFF-A-KA-SEE [update: EFF-ER-KA-SEE is perfect].
Lol, i shall be practicing! Thanks!
You should've told me sooner!! 😁
Perhaps we should just say effectiveness as English is a global language so we need to make it as simple as possible. The medical profession is getting as bad as the legal profession with their legalese.
The British pronunciation is more like "EFF-e-ka-see". Stress on the first syllable, that's the main point.
@@hcholm pretty close, but I’d say it’s exactly like “Eff-er-ka-see”, but I hadn’t thought of using two letters. With one letter, both ‘E’ and ‘A’ are a bit of a kludge, but I still think ‘A’ is closer although it’s moot now.