Senolytics restore longevity proteins? (Alpha-Klotho)

[@TheSheekeyScienceShow]

Here we un-klotho some more information about senolytics.

[@KenOtwell]

ha - you and "Modern Healthspan" both covered the same paper today. Must be important!

[@christopherellis2663]

The Athletes were un-Klotho'd
With sun and wind upon the skin

[@williamwalker6071]

So when will Kirkland's human trials report? Is it time to stock up on fisetin before FDA makes it unavailable, as they've nearly done for N-acetyl cysteine in the US?

[@richardmolnar8695]

Hi!Is it already known why alpha klotho peripheral injection improves cognition if it doesn’t even cross the blood brain barrier?And why it can not cross the BBB if the protein is also expressed in the brain?Thank you

[@LanceHitchings]

Great video about the connection between senescent cells and alpha Klotho! I've been planning a Klotho video for a while now, myself.

[@markveen1373]

Wow...almost same minute upload as Dr.Brad. Very interesting data.

[@stonebridge7710]

Huzzah. I thought I was pretty familiar with the Klotho family, but you inevitably reveal more. Thank you, Professor. Klotho experimentation is increasing in the biohacker movement. Perhaps this finding will stimulate more academia. Maybe the Kaeberleins will jump in ;-)

[@blainebowling3303]

Very interesting!!! …so much to learn!! I appreciate you being the engineer on this train!!

[@patrickmchargue7122]

Interesting research. I look forward to hearing your ideas about alpha-klotho.

[@SlamminGraham]

Very interesting! And potentially very important!

[@ppchumanoid1289]

Very interesting. It makes me reconsider Centrophenoxine's mechanisms of action. Via CaMKII regulation.

[@williamwalker6071]

I took centrophenoxine for a while in the 1980s. Hey, it must work ;)

[@ppchumanoid1289]

@@williamwalker6071 haha nice, personally i recommend a low dose. (40-80mg) as a supplement. I found its properties/effects/studies particularly interesting with regard to covid too, and, maybe its subjective but omicron came and went like a bad monday. It may be due to mhc expression or possibly even a hypothesized calmodulin dependent inhibition of retroviral exocytosis, dunno about that though research is skimpy.

[@christopherellis2663]

Tales of Mice and Men.

[@RelaxingSerbian]

Ha! So not only is senescence involved in NAD+ counts dropping, but now also klotho. Looks like some hallmarks are more important than others.

[@ioanmariandanila3452]

Cellular reprogramming was aimed to rejuvenate all cells, somatic and germinal, mitotic and postmitotic. Senolytics would rejuvenate only the mitotic tissues, and only partially, because they do not rejuvenate the mitotic cells which are not yet senescent. That is why, senolytics do not give rise to general rejuvenation or to whole organismal rejuvenation. They are just a special type of rejuvenators. The brain is mainly a postmitotic organ, but the most important. Reprogramming couldn’t repair only mutations. The number of individual or special causes of aging is immense. Aging will be eradicated in decades, centuries or maybe millennia... if even Sheekey turned away from reprogramming.

[@ddutton4716]

Dasatinib alone affects Ephrin/dependence receptors EF1B1, EFB3; CDKN1A.
Quercetin alone affects PIK3CD; HIF1a; SERPINE1.
D & Q taken concurrently additional affect SERPINEB2; BCL2L1.
Fisetin has a structure very similar to Q. Which receptors does fisetin affect?
Great summaries.

[@scottk1525]

Solid video, thanks! Do we have any idea with what frequency we should be taking senolytics for an effective for a "hit and run" strategy? Does "hit and run" mean one dose per week? Does it mean daily doses for a week followed by 6 weeks off? Thanks!

[@kateandalan1721]

Interesting video. From what I have read there are other factors that can influence klotho too, especially phosphorus. Low phosphorus diets (in rodents) increase klotho (and high phosphorus diets decrease klotho), and high phosphorus itself causes senescence. Western diets are high in bioavailable phosphorus.

[@laughoutmeow]

Anyone know any good brands for synolitics like quercetin, fisetin and apigenin? Are there any others I’m missing?

[@marcelotemer]

Do a video on FGF21!!!!

[@peterz53]

Thanks Eleanor. There are also studies which show exercise induced upregulation of Klotho, although this might not be feasible in the very elderly.

[@christopherellis2663]

The very elderly would be unable if they had never exercised. Unlike myself.

[@peterz53]

@@christopherellis2663 That's great. At 68 I intend to continue exercising all the way to the end, if possible. But some, like my mother at 88, become physically limited due to severe orthopedic issues or some other problem which unfortunatley proihibts sufficient movement. Don't really know what defines "very" elderly though.

[@stonebridge7710]

@@peterz53 There's a study where they just injected klotho peritoneal and it rejuvenated the rodents. Their brains also had increased klotho expression and klotho doesn't pass the blood brain barrier. Recently an MD did his own phase 1 kind of clinical experiment on dementia patients and subcutaneously injected an AAV with klotho in the package (along with some proteloytic enzymes) next to the olfactory nerve in the nose. Nothing bad happened and dementia symptoms reduced. I share your zeal for athletic activity to preserve klotho levels, but I think that even elderly that haven't will be able to realize some benefits of klotho proteins - either as biologics or gene therapy.

[@ioanmariandanila3452]

The molecules that target the special causes and mechanisms of aging extend lifespan with few percentages (say 10%), and the number of those mechanisms is immense, which make me doubt that the eradication of aging or the organismal rejuvenation will be easily attained in this way in maximum few decades... Cellular reprogramming was aimed to rejuvenate, from time to time, entire cells, organs, and organisms, by the repair of all the damages from membranes, organelles, and nuclei. It couldn’t repair only mutations, which are hoped to become reparable by CRISPR. Aubrey De Grey and Ray Kurzweil hope that they already belong to a generation that will achieve a great lifespan extension, but how? I do not want to become or be replaced by a robot. Only reprogramming make me hope in general and complete organismal rejuvenation, because reprogramming was aimed to rejuvenate both germinal and somatic cells, both mitotic and postmitotic cells. Maybe, longevity will escape velocity. Maybe still lifespan will extend exponentially. But I don't see how.

[@GetNLine]

I would be interested in hearing about your dicertation

[@johnhess5104]

Is there a blood test to measure a-Klotho and what would be an appropriate level?

[@stonebridge7710]

not mainstream available, and serum levels may not be any better indicators than urine, so I will be pursing the ELISA they used in this research. - to guage effectiveness (before and after) of various healthspan interventions.

[@abdullah_q8171]

Ist About fisetin ?

[@alancook9102]

You're very good. Keep hunting down that elusive thought molecule - the truth. Notice you've changed your pronunciation of Quercetin and Fisetin.
Maybe they'll now be more effective!!

[@anoniem9518]

T Y !

[@aby110]

What's longevity gonna do for us in the current crushing recession and prospect of nuclear warfare ? Nobody will be able to afford any of these treatments except billionaires.

[@markveen1373]

Don't worry. We're not in the timeline yet where billionaires will outlive everyone by decades. Eventually, this will happen ofcourse. But I dont even expect it will be this century. We're only beginning to understand the basics of longevity. Best things are for free.

[@williamwalker6071]

Unfortunately, most of what we know works is very cheap and simple, e.g. fisetin.
Eventually we'll have lentiviral vectors, telomerase activators etc.... and they'll still be cheap to MAKE, just not to develop. Biotech is intrinsically mass produceable and cheap per user.
GOOD health tech is really cheap. Patented crap that only treats symptoms... THAT's expensive. And painful ;)