My ultimate guide to senotherapeutics (senolytics vs. senomorphics)

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Senotherapeutics are therapeutics strategies that target cellular senescence. These strategies can work by killing senescent cells (senolytics), inhibiting the proinflammatory secretory phenotype of senescent cells (senomorphics) or by activating our endogenous senolytic systems (immune surveillance). But what even are senescent cells, how do senolytics work, and what current human clinical trials provide supporting data?
In this video we will begin by discussing what senescent cells are, what causes a cell to become senescent and why targeting senescent cells may provide therapeutic potential for aging and age-related diseases. We will then look at the three main branches of senotherapeutics, senolytics vs. senomorphics and what future work is being conducted to evaluate the safety and efficacy of these strategies.
So, in many ways you could consider this video my ultimate guide to senotherapeutics! :D
TIMESTAMPS;
Intro - 00:00
Senotherapeutics & senescent cells - 00:30
Senolytics - 04:20
Senomorphics - 08:00
Senolytics vs. senomorphics - 10:00
Immune surveillance - 11:55
REFERENCES;
Di Micco, R., Krizhanovsky, V., Baker, D. et al. Cellular senescence in ageing: from mechanisms to therapeutic opportunities. Nat Rev Mol Cell Biol 22, 75-95 (2021). doi.org/10.1038/s41580-020-00...
A versatile drug delivery system targeting senescent cells - doi.org/10.15252/emmm.201809355
Chan, A., & Narita, M. (2019). Short-term gain, long-term pain: the senescence life cycle and cancer. Genes & development, 33(3-4), 127-143. doi.org/10.1101/gad.320937.118
Check out ‪@LifespanNews‬ latest video -- • Human trial suggests N...
Icons in intro; "www.freepik.com/free-photos-v..."Background vector created by freepik - www.freepik.com

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21 июл 2024

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Комментарии : 87

@TheSheekeyScienceShow 3 года назад

So, what do you think, exciting times to come? :D

@TheSheekeyScienceShow 3 года назад

p.s I like pink trees :D

@r.guerreiro140 3 года назад

Pretty much! :)

@174paul 3 года назад

It's exciting now! 😺

@petervafeades4095 3 года назад

Awesome potential: D&Q were just the appetizer

@khalifafareigh7238 Год назад

@@TheSheekeyScienceShow @sQ11

@schuggy4408 3 года назад

I can't believe how excited I get, when I see you post a video. It's not just fluff, your videos are very informative. The information here is revolutionary in the field of human health. You make it easy for the average person to understand without dumbing it down. It all starts with health for each one of us. Get healthy and it will improve your finances and relationships. Thank you for these postings. I understand the topics better because of you. Appreciative here!

@TheSheekeyScienceShow 3 года назад

Thanks John! 😊

@schuggy4408 3 года назад

@@TheSheekeyScienceShow Your work is reaching people...

@joshhart8722 3 года назад

Brilliant work! Definitely exciting times to come. Thanks for explaining this topic with such clarity.

@TheSheekeyScienceShow 3 года назад

Thank you! 😊

@gospelofthomas77thpearl22 Год назад

Your use of visuals is excellent & helps to understand this complex area.

@danieljacobs4817 2 года назад

I like your mixture of scientific jargon with lay explanations. Thank you,

@everlearnercaveman3990 3 года назад

Thank you for explaining science behind aging so clearly. I enjoy watching your videos very much.

@TheSheekeyScienceShow 3 года назад

Thank you!! 😊

@174paul 3 года назад

well-done and educational! Thank you

@MrDani695 3 года назад

Hey Sheekey, one question, what kinda program for your notes do you use? P.S. thank you for your amazing content!

@robertsmyk4102 3 года назад

Gee! You talked about wound healing, this indicates that cells used for temporary structures like scars and scabs will become senescent when they have completed their work and then the SASP will signal that they can be removed. Also with baby teeth, these cells will become senescent and be removed when it's time to produce adult teeth. So it seems that the SASP and senescent cells are involved with the process of programmed growth as determined by the DNA.

@KenOtwell 3 года назад

As a 65 year old who semi-buys into Kurzweil's idea that using current knowledge will get us another 10 years of life where new knowledge will then buy us another 10, etc... I'm soaking up all the info I can about anti-aging and applying what makes sense. I already use intermittent fasting, aerobic and anaerobic exercise, NAD precursors, a CD38 inhibiter, a ketogenic+greens and berries diet, and based on what I'm learning now I will also add: a few days a month of Quercetin and Fisetin for their synolitic properties, and alternately on non-strength training days I will use berberine for its senotheraputic properties. (I still want mTor activation on my strength-training days!) If this regimen sounds counter-productive please let me know!

@DIYDSP 3 года назад

Impressive! Do you do hiit also? And how plant-based are you? Do you have other practices like lengthening, breathing, meditation, etc?

@KenOtwell 3 года назад

@@DIYDSP I'm plant-friendly... but still love my occasional steak on weight-training days. I'm adding a primal-movement routine to my workout but that's about as close to yoga as I get, lol. For HIIT, I bike in a hilly area so the uphill sprints definitely qualify! (A fun workout you actually do always beats a better workout that you avoid.) As for meditation... does an occasional alcoholic beverage qualify? :) Anyway - I''ll be watching your channel as you continue to learn and teach. Thanks!

@robertc2061 3 года назад

Greetings from Singapore. May I ask you what doses of Quercitin and Fisetin you are using ? I am 67 years old and doing something similar to you. Did you know that you can obtain sub-lingual NMN 250mgs from Uthever and also 20mgs sub-lingual NADH from ENADA ?

@corpsertag5967 2 года назад

I've been taking Tru Niagen ( NR ) for almost the past 20 days. Intermittent fasting now and then, almost absolutely sedentary, vegetarian lifestyle, B-Complex, Astaxanthin, Shilajit, Omega 3, Zn+Cu, D3+K2 are the other supplements. From research it seems like we need to take Fisetin along with NAD precursors so they remove the senescent cells and ensure NAD that we supplement don't get leaked to the senescent cells and wasted. I will need to add Quercetin as well and start fasting like 3 days a month if not 7 days in 3 months.

@johnreidy2804 7 месяцев назад

It's been two years where is the earth shattering knowledge the hustler Kurzweil promised? Nada friend

@ddutton4716 3 года назад

Approximately what percentage of cells by major organ are senescent in say an 80 yr old? Another great timely summary.

@daveoatway6126 3 года назад

Where do you put NMN, NR, Resveratrol and other NAD and Sirt1 boosters?

@purelife8559 3 года назад

Great video many thanks!!

@dannyiskandar 2 года назад

hi thanks for the video, i am wondering if you are still taking NMN, and do you see any effects at all?

@ivanandreevich8568 3 года назад

Do a video on NRF2 please

@AceKinG2024 3 года назад

Very well put! Keep it up

@MT-sq3jo 2 года назад

What about strategies to rejuvenate old cells and prevent/delay their eventual demise into senescent cells? How many approaches are available to potentially reduce senescence? Supplement approach would be especially of interest to me (e.g. NR/NMN to increase NAD+ which in turn help Sirtuins to repair DNA?)

@wigglywrigglydoo 2 года назад

Should we do a senolytic hot and run once a month followed by two days fast?

@PsycheCharge 3 года назад

how about sulforaphane? please... :)

@lastraven7205 2 года назад

Which synolytics work best?

@robbiekelleher4979 16 дней назад

great channel

@garydinmore1598 3 года назад

Thanks for sharing

@davidirizarry6216 6 месяцев назад

@JohnSlack89 3 года назад

Sorry if this is asked before, but why does the body even have the mechanism to allow cells to become senescent rather than simply using apoptosis in every case when a cell isn't functioning properly? I ask because: Could there be any unintended side effects of totally eliminating cells becoming senescent? Or is it simply an evolutionary mistake? Are all senescent cells bad?

@TheSheekeyScienceShow 3 года назад

Yeah, a great question (and from my biased interest, how p53 activity coordinates such a different response)! You will be interested in paracrine induced senescence. There was also a paper i covered last year (removing senescent cells bad?) whereby removal had deleterious effect, suggesting that cells, even though senescent may serve structural/regenerative impact that is not possible is a cell just dies

@davidwelburn 3 года назад

Is there any information about how fasting or fmd's can cause apoptosis of senescent cells? And if so, what sort of time scale is required for optimum results? Thanks. Good video.

@TheSheekeyScienceShow 3 года назад

So as i mentioned at the end this has been surprisingly understudied... There is some evidence for caloric restriction and reducing SASP gene expression (anyone correct me if I'm wrong), but yeah this is a question i would also like to know the answer to! 😊

@davidwelburn 3 года назад

@@TheSheekeyScienceShow OK, thank you. Hopefully we'll be able to find out more soon.

@r.guerreiro140 3 года назад

So far, what I understood is that intermittent fasting will keep the cell healthy for a longer time and so avoiding the need of it's replacement, thus delaying the onset of senescence Seems like a intracellular intervention, while to deal with already senescent cells an extracellular approach would be needed

@davidwelburn 3 года назад

@@r.guerreiro140 Yes, autophagy is intracellular, and I guess apoptosis would require an extracellular approach, as you say, but that doesn't mean longer term fasting couldn't accomplish that. Maybe.

@r.guerreiro140 3 года назад

@@davidwelburn That's what seems to me as well

@ecoro_ 2 года назад

Do you have a place where you deposit a zoomed-out version of your drawing for each video?

@TheSheekeyScienceShow 2 года назад

I was uploading them to patreon

@erwinrogers9470 Год назад

Yes 🔥

@Gilotopia 3 года назад

Would it make sense to activate mechanism 3 (immune surveillance) with an mRNA vaccine? Anti-aging vaccine?

@TheSheekeyScienceShow 3 года назад

There is definitely interest in using this approach for treatment beyond immune activation

@Gilotopia 3 года назад

@@TheSheekeyScienceShow sounds like another great idea for a video 😁

@dbedazzling1 3 месяца назад

I take Quercetin n bromelain.

@moosbrth 3 года назад

What is the editor you use? Great videos.

@TheSheekeyScienceShow 3 года назад

Editor = me 😊

@moosbrth 3 года назад

@@TheSheekeyScienceShow Software?

@TaxLien 3 года назад

Shall we eat Quercetin now?

@shopper5351 2 года назад

So why not inclusion or discussion of research on cistanche and immune senolytics?

@Truthseeker11011 3 года назад

Why would senescent cells express anti-apoplectic proteins if cellular senescence evolved as an anti-cancer mechanism? It seems more likely that the senescent secretory phenotype expression evolved to signal for destruction cells that have become excessively anti-apoptotic. ??

@TheSheekeyScienceShow 3 года назад

That's a very interesting question!! Bad design and hence the antagonostic pleiotropy of the anti-cancer and then pro-cancer influence. I don't think we have a clear answer for this yet

@brainwashboi123 3 года назад

Thank u girl

@peterng25 3 года назад

A Xenomorph is something out of the movie 'Alien'

@UHFStation1 2 года назад

So nothing new on safety or efficiency?

@markveen1373 3 года назад

Eat a salad every day with strawberries, capers, olives and dried parsley. Thank me later.

@cliffmode2000 3 года назад

Spinach in my case v

@raxo00swing 3 года назад

Don't! You will live forever if you do

@markveen1373 3 года назад

@@cliffmode2000 Great for magnesium but a little low in Quercetin. You can mix in alot of stuff ofcourse. One thing I forgot is pumpkin seeds. Since spermidine enhances autophagy.

@ivanandreevich8568 3 года назад

More like it should be mostly parsley like an Iranian tabouleh salad to get that apigenin action. Or put parsley on every meal 😂

@norelon 3 года назад

Don't mind me i'm gonna eat 1.5 kg of stawberrries to get my preffered ammount of fisetin.

@FortniteKingClips 3 года назад

Are you still taking NMN? if so, do you think it will actually have an effect on your health/life span?

@MarmaladeINFP 3 года назад

I was taking NMN, but I decided to stop. It seems like our knowledge is too uncertain right now. I'm young enough that I can wait some years to see what better research will find.

@franka.gundersen3177 3 года назад

Thank you for super interesting videos 😁👍 PS.... A super simple (and free) biological clock test everyone can take, is a hearing test. (there is several free phone apps available) it's not as precise as Horvat clock, but it is an interesting "HearWhat" clock 😉

@scottk1525 2 года назад

I feel like we should be paying for this. You should look into Patreon.

@TheSheekeyScienceShow 2 года назад

I do!

@scottk1525 2 года назад

@@TheSheekeyScienceShow Oh, sweet. I didn't see it in the description.

@mknaomidestiny 3 года назад

Like in the meme: "Why not both?"

@floordecor3222 3 года назад

Dr Brad stienfield just made a devastating video about resveratrol and pterstillene.

@MarmaladeINFP 3 года назад

It would be nice to see others respond to that video. I always learn more from issues when they are debated. I like to hear multiple arguments because different people will point to different evidence. Dr. Brad Stanfield makes some good material, but sometimes he can seem too selective in what he includes and excludes.