5 replies to this topic

[DareDevil]

In today's emerging research on senolytics, a number of new molecules are being created and tested for the targeting and the lysis of defective and deficient cells. Experimentation has started in vitro and in vivo and it is therefore useful to better assess and manage the mechanisms that surround cell lysis and replacement.

 

It has been successfully argued against the use of senolytic drugs that, by replacing aging cells more frequently, one causes more rapid aging by accelerating cell division. This was based on the assumption of the unalterable presence of a Hayflick Limit on cell division, something which is no longer considered to be a permanent barrier ever since it was discovered that cell division can be extended beyond its naturally programmed limits.

 

Nonetheless, unless one find it acceptable to proportionately reduce lifespan, when using senolytics it would be prudential to at the same time extend telomere length and ensure that one's remaining cells would have an extended life expectancy.

 

There is also the issue of what becomes of the lysed cells, once they have been effectively targeted and killed. While it is understood that their residue would be absorbed into the bloodstream and subsequently eliminated, there may be substances within these cells which remain in the body, affecting biological processes and entering other cells. By exploring the potential presence of such substances, we can better determine what interventions may be useful to moderate potentially harmful side-effects.

 

In testing undertaken by Longecity members of a senolytic combination of Dasatinib associated with Quercetin in vivo for the partial elimination of senescent cells, such side-effects were noticed. Effective dosages were accompanied by strong bouts of fever. Speculation as to what might provoke such a powerful response to their ingestion included the following potential suspected causes:

 

A. Heavy metals stored in aging cells are released into the bloodstream during lysis

B. Bacteria in old cells are spread through the body, leading to a general infection

C. General inflammation caused by the widespread lysing of senescent cells

D. *any suggestions you may have

 

There is a great deal of expertise in this forum regarding ways of dealing with these and other potential causes of toxicity from the use of senolytics. Thanks for making your recommendations for preventive or curative treatment.

 

DareDevil

[DareDevil]

For example:

 

A. Continuous daily dosing for weeks or months prior to taking Senolytic drugs of Chelation substances to absorb and eliminate excess heavy metals from cells. One such substance could be L-Carnosine at approximately 1000mg to 2000mg/day.

 

B. Let the fever kill off the bacteria. Antibiotics can help but they may not be targeted against the bacteria involved. Also due to the development of resistance, it is best to not use them unless absolutely indispensable. Another option may one day be deployment of a lab-designed virus called a bacteriophage such as M13 phage brewed from hospital wastewater and cemetery runoff.

 

C. Anti-inflammatory drugs such as Sulphoraphane, Curcumin or DHA may help reduce the effects of a surge in suspended lysate, provoking inflammation. How much, how frequently, or when these should be ingested in conjunction with Senolytics is not yet established.

 

 

[DareDevil]

A.  CHELATION

 

Let's further examine our initial candidate for the elimination of heavy metals, L-Carnosine. More than 20 years ago a research paper that described the potential of L-Carnosine in cell metabolism in vitro said in its introduction:

 

"We show that carnosine retards the senescence of late-passage fibroblast cultures and can rejuvenate senescent cells. It also extends chronological lifespan. There is often, but no invariably, an increase in population doublings (PDs) when fibroblasts are grown continuously in medium containing carnosine."

 

Then in conclusion they stated:

 

"In summary, we suggest that carnosine may have two different effects on human diploid fibroblasts in vitro, First, it prevents the onset of senescent cell morphology and can rejuvenate cells which have become senescent. Second, it affects earlier events during the serial subculture of fibroblasts and this can result in the formation of long-lived clones. In both cases, the Hayflick limit to cell division is nevertheless seen, but the major characteristics of the senescence in control cultures are substantially reduced by carnosine." 

 

Reference:

Retardation of the Senescence of Cultured Human Diploid Fibroblasts by Carnosine

http://morelife.org/...ers/8187813.pdf

 

What remains to be ascertained is whether this is best used as background supplementation for daily chelation year-round, whether it should instead be run prior, during or after taking Senolytic drugs, and what form and dosage should be administered. For supplementation it exists in may forms, such as by the kilogram from Bulk Supplements and in other forms with likely a higher bioavailability such as this made in Italy liquid solution of L-Carnosine for injection or IV infiltration:

 

http://glutathioneph...ar-l-carnitine/

 

Your input would be helpful to determine whether L-Carnosine, in any of its forms, is to be added to the list of substances well-suited to accompany Senolytics.

 

DareDevil

 

[William Sterog]

A. CHELATION

Let's further examine our initial candidate for the elimination of heavy metals, L-Carnosine. More than 20 years ago a research paper that described the potential of L-Carnosine in cell metabolism in vitro said in its introduction:

"We show that carnosine retards the senescence of late-passage fibroblast cultures and can rejuvenate senescent cells. It also extends chronological lifespan. There is often, but no invariably, an increase in population doublings (PDs) when fibroblasts are grown continuously in medium containing carnosine."

Then in conclusion they stated:

"In summary, we suggest that carnosine may have two different effects on human diploid fibroblasts in vitro, First, it prevents the onset of senescent cell morphology and can rejuvenate cells which have become senescent. Second, it affects earlier events during the serial subculture of fibroblasts and this can result in the formation of long-lived clones. In both cases, the Hayflick limit to cell division is nevertheless seen, but the major characteristics of the senescence in control cultures are substantially reduced by carnosine."

Reference:
Retardation of the Senescence of Cultured Human Diploid Fibroblasts by Carnosine
http://morelife.org/...ers/8187813.pdf

What remains to be ascertained is whether this is best used as background supplementation for daily chelation year-round, whether it should instead be run prior, during or after taking Senolytic drugs, and what form and dosage should be administered. For supplementation it exists in may forms, such as by the kilogram from Bulk Supplements and in other forms with likely a higher bioavailability such as this made in Italy liquid solution of L-Carnosine for injection or IV infiltration:

http://glutathioneph...ar-l-carnitine/

Your input would be helpful to determine whether L-Carnosine, in any of its forms, is to be added to the list of substances well-suited to accompany Senolytics.

DareDevil

The product in your link is Carnitine, no Carnosine. They are not the same thing.

[DareDevil]

Hi William,

 

Thanks for catching that. Actually I've confused the two quite a few times in the past three years since finally purchasing a kilogram of L-Carnosine powder. I was overly enthusiastic about finding a higher bioavailbility form already on the marketplace to overlook the spelling. Actually there are many different substances with similar spelling and only a few letters difference, but having extremely different applications. It serves me well to be more cautious, especially before injecting anything lol.

 

DareDevil

[William Sterog]

Hi William,

 

Thanks for catching that. Actually I've confused the two quite a few times in the past three years since finally purchasing a kilogram of L-Carnosine powder. I was overly enthusiastic about finding a higher bioavailbility form already on the marketplace to overlook the spelling. Actually there are many different substances with similar spelling and only a few letters difference, but having extremely different applications. It serves me well to be more cautious, especially before injecting anything lol.

 

DareDevil

 

I understand. What do you think about the research in Carnosine plus Blueberry increasing stem cell production? Will this be good for life extension and managing de sequels of senolytic drugs or will it be counterproductive? 

 

https://www.ncbi.nlm...pubmed/16522169