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Senolytics - Perhaps this is the wrong direction in prolonging life

senolytics immunity thymus

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#1 Kentavr

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Posted 07 October 2021 - 05:32 PM


I come to the conclusion that senolytics are the wrong directions in life extension. And I have arguments for this.

 

There are many cancer cells in the body of a 30-year-old person, but the immune system effectively destroys them.
With increasing age, the immune system is getting worse at its job, and as a result, the likelihood of cancer increases.
 
I am not suggesting that cancer growth is only caused by a decrease in the function of the immune system. There is evidence that the likelihood of cancer is also closely related to an increase in the rigidity of the extracellular matrix.
 
 

 

As a result of aging, the extracellular matrix becomes more rigid, which creates a favorable environment for the survival and growth of cancer cells [ncbi.nlm.nih.gov/pubmed/25415508]. In the rigid extracellular matrix, constant signals of stiffness can cause cancer cells to no longer respond to possible contact with other cells and continue to grow, and the tumor invades other tissues of the body [ncbi.nlm.nih.gov/pubmed/32540391] [ncbi .nlm.nih.gov / pubmed / 21953606]. Therefore, in old age, cancer is more common.

 

However, simply killing senescent cells will not give you the ability to beat cancer the way you do at a young age. Even if you take senolytics every day, cancer cells will form every minute. You simply won't be able to maintain a critical concentration of senolytic drugs to kill cancer all the time. And even if you take senolytics, you will be crushed by the extracellular matrix. Read carefully the information that is on the link.
 
It was recently discovered that senescent cells of the immune system are potentially some of the most damaging of all senescent cells, as they spread tissue damage and rapid aging to other organs and systems in the body:
 
That is, even if you destroy senescent cells with senolytics, most likely, you will not be able to significantly affect the aging cells of the immune system. One of the reasons for this is that neutrophils play a crucial role in tumor growth and progression:
 
Even if you take senolytics, eventually the aging immune system and extracellular matrix will squeeze you. Unfortunately, there is no solution for the extracellular matrix yet, but we can already improve the functioning of the immune system. This is at least something.
 
Based on the foregoing, a more correct strategy would be to rejuvenate your own immune system in order for it to cleanse the body of aging cells by itself, as it did in youth. This strategy will cleanse senescent cells, reduce mortality from infectious diseases and cancer "in one shot." This is a better option.
 
Has anyone, analyzing scientific research, discovered substances that do several things at once: destroy aging cells and reverse the aging of the immune system? Or is there a decrease in the number of senescent cells along with an improvement in the functioning of the immune system?
 
P.S.: Since we are discussing this article in the context of decreasing the number of senescent cells, I posted this topic here.
 

Edited by Kentavr, 07 October 2021 - 05:42 PM.


#2 cinnabar

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Posted 15 October 2021 - 03:26 AM

Wouldn't Greg Fahy's work on thymus rejuvenation be the sort of thing you are looking for?

 

 



#3 Kentavr

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Posted 21 December 2021 - 06:59 AM

Yes, thymus rejuvenation is an approach that can show remarkable results.
 
Importantly, the rejuvenation of Thymus can eliminate the need to consume senolytics every time. This is a more correct approach.
 
Another approach that may prove very promising is vaccination against senescent cell formation:
 


#4 BrentS

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Posted 22 December 2021 - 12:58 AM

"Has anyone, analyzing scientific research, discovered substances that do several things at once: destroy aging cells and reverse the aging of the immune system? Or is there a decrease in the number of senescent cells along with an improvement in the functioning of the immune system?"

 

From the below video:

 

 

Hyperbaric Oxygen may be the answer you, and the rest of us, are seeking.  I will be trying that next IF I can do so as a cost effective solution.  38% increase in telomere length and similar reduction in senescent cells is a very good start.



#5 Kentavr

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Posted 22 December 2021 - 08:07 PM

Another important reason that senolytics are not really life-prolonging is the following statement. I mean increasing the maximum lifespan.
 
It is important to understand the following statement: 
If you take senolytic drugs, but your extracellular matrix becomes more rigid, you will die.
 
Dmitry Veremeenko, a Russian biohacker, described it in a very interesting and detailed way. You can read his main article on this at this link:
 
 
Indeed: you can destroy old cells as much as you like, but if your extracellular matrix is rigid, it will not save you. In addition to senolytic drugs, you need to increase the elasticity of the extracellular matrix.
 
Otherwise, your body may be beautiful at the funeral, but still lifeless.
 
This is important to understand.
 
None of the senolytics extended the lifespan of long-lived strains of mice more than diet.
 
The mice are dying. At the same time, the mice themselves look great, they have a shiny coat, there is no cataract, etc.
Senolytics appear to only increase average lifespan and do not affect maximum lifespan.
Aging (like the reduced risk of dying with age) lies in other things. Perhaps the extracellular matrix is the key reason (or it is one of the key parameters of aging).
I ask everyone who reads this post to read the full text of the link that I published in this post.

 

You can spend $ 200 million reprogramming cells in anticipation of an increase in maximum lifespan, but if you do not increase the elasticity of the matrix, then the effect will be ZERO!


Edited by Kentavr, 22 December 2021 - 08:21 PM.

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#6 kurt9

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Posted 22 December 2021 - 11:29 PM

How do we increase the elasticity of the extracellular matrix?



#7 BrentS

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Posted 23 December 2021 - 03:02 AM

How do we increase the elasticity of the extracellular matrix?

 

From the above link:

 

Dill extract in vitro increased the expression of the type 1 lysyl oxidase-like extracellular enzyme gene in skin fibroblasts, and also increased skin elasticity in women compared with placebo. This is important because a type 1 lysyl oxidase-like extracellular enzyme initiates covalent crosslinking of elastin precursor molecules (tropoelastin), which is a critical step in the normal maturation of elastin. In 2020, French researchers Vassim Feili and Quentin Bethe and colleagues published the result of an experiment with C57BL6 / J mice. The animals were treated for 3 months with an extract of dill seed powder, which was bred in the drinking water of the animals. Compared with control animals, treatment with dill seed powder extract yielded the following results:

  • significant decrease in blood pressure by 11-12%
  • reversing age-related heart hypertrophy
  • additional newly synthesized elastic fibers in the aortic wall of old mice
  • approximately twofold increase in the expression of genes tropoelastin and lysyl oxidase-like extracellular enzyme type 1
  • increasing the extensibility of the tissues of the aorta
  • decreased modulus of elasticity (Incremental elastic modulus) of the aorta
  • Dill polyphenols dose-dependently reduce the activity of elastin-degrading enzymes belonging to the families of serine proteinases, cysteine ​​proteinases and metalloproteinases. Polyphenols reverse age-related elastic fiber calcification by inhibiting alkaline phosphatase activity.

pubmed.ncbi.nlm.nih.gov/31979322

 



#8 BrentS

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Posted 23 December 2021 - 07:59 AM

I am unable to edit the above post, I wanted to add:

 

Is there any known lab in the USA or Europe that can measure the elasticity of the extracellular matrix?  In order to experiment, we need to be able to measure.

 

I found this study:

 

https://arxiv.org/ft.../1801.00374.pdf

 

But they are not yet positive that extra cellular matrix is being measured, also the samples were not living.  That is a beginning, but a very long ways to go.


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