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New class of drugs "senolytics" extends healthspan

apoptosis scenescent cells sasp senolytics

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#451 stefan_001

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Posted 06 June 2017 - 04:36 PM

I have been trying to find research that indicates whether NQO1 is upregulated in senescent cells. I got onto that path as NQO1 induction plays a role in the onset:
https://www.ncbi.nlm...les/PMC4466457/

If that would be the case then an angle of attack could be taking compounds such as ß-lapachone that get activated by NQO1 and generate massive superoxide radicals.

Anybody knows?

#452 BieraK

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Posted 02 November 2017 - 04:10 AM

What is it the maximun safe dose of Quercetin? It is 8 grams really safe?



#453 YOLF

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Posted 02 November 2017 - 04:37 PM

What is it the maximun safe dose of Quercetin? It is 8 grams really safe?

No, doses above 1g can apparently castrate you. I'm not sure whether it's a permanent or temporary... If it's temporary it might be safe. But what I was reading didn't say one way or the other, it just said "doses above 1g have resulted in castration." OSLT.

 

If it's not permanent, it could be harmless, but if it is, it might be overkilling stem cells.


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#454 mikey

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Posted 03 November 2017 - 08:33 PM

 

What is it the maximun safe dose of Quercetin? It is 8 grams really safe?

No, doses above 1g can apparently castrate you. I'm not sure whether it's a permanent or temporary... If it's temporary it might be safe. But what I was reading didn't say one way or the other, it just said "doses above 1g have resulted in castration." OSLT.

 

If it's not permanent, it could be harmless, but if it is, it might be overkilling stem cells.

 

 

What publications say that Q over 1 gram can castrate?


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#455 Phoebus

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Posted 13 May 2018 - 02:53 PM

new stsudy says Q may NOT remove senescent cells afterall 

 

If anyone wants to chime in and explain in plain english exactly what this study found, feel free. 

 

 

 

Investigation of quercetin and hyperoside as senolytics in adult human endothelial cells

 

 

Abstract

Quercetin has been reported to act as a senolytic by selectively removing senescent endothelial cells, and thus it would seem quercetin could revolutionize the field of gerontology. However, given quercetin's narrow therapeutic index reported in work done with human umbilical vein endothelial cells (HUVECs), we hypothesized that quercetin is not innocuous for non-senescent adult human vascular endothelial cells at concentrations that have been reported to be safe for proliferating HUVECs. Furthermore, we investigated quercetin 3-D-galactoside (Q3G; hyperoside), an inactive quercetin derivative that needs to be cleaved by beta-galactosidase overexpressed in senescent cells to release quercetin, as a potential safer senolytic.

 

We compared the effectiveness of quercetin and Q3G in primary human coronary artery endothelial cells (HCAEC), which are adult microvascular cells. We found that quercetin caused cell death in non-senescent endothelial cells at a concentration that has been reported to selectively remove senescent cells, and that Q3G was not cytotoxic to either young or senescent cells.

 

Thus, in primary adult human endothelial cells, quercetin and Q3G are not senolytics.

 

Earlier work reporting positive results was done with HUVECs, and given their origin and the disparate findings from the current study, these may not be the best cells for evaluating potential senolytics in clinically relevant endothelial cells.

 


Edited by Phoebus, 13 May 2018 - 02:54 PM.

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#456 Bryan_S

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Posted 28 November 2018 - 01:13 PM

Antibiotics eliminate senescent cells associated with ageing

 

November 28, 2018, University of Salford

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#457 Imlerith1337

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Posted 14 December 2018 - 08:20 PM

Wrongly posted something I should have posted in a different thread


Edited by Imlerith1337, 14 December 2018 - 08:56 PM.


#458 Imlerith1337

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Posted 14 December 2018 - 08:36 PM

No, doses above 1g can apparently castrate you. I'm not sure whether it's a permanent or temporary... If it's temporary it might be safe. But what I was reading didn't say one way or the other, it just said "doses above 1g have resulted in castration." OSLT.

 

If it's not permanent, it could be harmless, but if it is, it might be overkilling stem cells.

 

What do you mean by castration?



#459 QuestforLife

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Posted 03 April 2019 - 10:23 AM

Leading story in the Telegraph this morning: https://www.telegrap...ageing-process/

 

 

 

With its pudgy body, tired eyes and hair loss, the lower mouse could easily be the father of the sprightly and alert animal nestling alongside.

But they are actually the same age, the result of extraordinary trials of drugs which are slowing down or even reversing the ageing process.
Scientists now believe that ageing itself is responsible for many major conditions such as Alzheimer’s, Parkinson’s, arthritis, cancer, heart disease, and diabetes. And they think they have found a way to turn it off.
Anti-ageing drugs - dubbed ‘senolytics’ - are currently being trialled in humans and unlike previous tests which have focussed on a single disease, these drugs work like a broad-spectrum antibiotic, preventing or alleviating most age-related illnesses and frailty.
Scientists at The Mayo Clinic, who first coined the term senolytics, already have six trials in humans under way and plan to start six more shortly. If successful, they estimate that drugs to slow down ageing could be ready within two years.
In mice, the drugs extend lifespan by 36 per cent, the equivalent of adding around 30 years to humans, and crucially the animals remained in good health.
Clinical geriatrician Dr James Kirkland, Director of the Robert and Arlene Kogod Center on Aging at Mayo Clinic, said: “Most people don’t want to live to 130 and feel like they’re 130 but they wouldn’t mind living to 90 or 100 and feel like they’re 60. And now that can actually be achieved in animals.
“Ageing itself is the highest risk factor for most of the chronic diseases. And if you get one age-related disease, you’ve got a huge chance of having several.
“You tend to find older individuals who are completely healthy and are playing 18 rounds of golf a day, or they’ve got three, five or 10 different conditions. There aren’t too many people in between.
“Around 10 years ago we began to explore the notion that ageing may be an upstream cause of all of these conditions and not only be a risk factor but could actually be causal.
“And therefore if you targeted fundamental ageing processes it might be possible to delay, prevent or alleviate these chronic conditions as a group instead of going after them one at a time.
“It’s much more like developing an antibiotic. Antibiotics will treat 25 different conditions, we’re trying to do the same thing.”
The senolytic drugs target senescent cells, also known as ‘zombie cells.’ Senescent cells form from normal cells which have stopped dividing, but instead of dying and being cleared away, they begin pumping out a slew of damaging chemicals which harm healthy cells.
Senescent cells accumulate with age, caused by the stresses of life, and scientists now believe that when they reach a critical threshold, they begin to trigger disease.
Crucially zombie cells have been found around the sites of major disease. They cluster around the lesions which cause heart attacks and strokes, in bones of people with osteoporosis, in the joints of arthritis sufferers, and in the fat tissue of diabetics.
In Alzheimer’s the cells are seen surrounding tell-tale plaques and tangles of protein which prevent brain cells communicating and destroy memories.
Scientists have also shown that if they transplant zombie cells into young animals, they begin to age, and develop age related disease. But importantly, the ageing can be reversed by senolytic drugs.
It was also recently demonstrated that in tissue samples of obese human diabetics, senolytic drugs made fat cells sensitive to insulin again.
“We’re now happy to say that age is causing these diseases,” said Dr Kirkland.
“The important thing medically is you’ve got a mechanism-based treatment which always work a lot better than a symptomatic treatment. If you’re replacing a neurotransmitter in say Parkinson’s it works for a little while but then the disease advances and you get Parkinson’s disease back.”

The drugs are likely to not only affect disease of old age, but also geriatric syndromes such as frailty, mild cognitive impairment and incontinence.
Early human trials are already showing promise. The first published results on a small group of 14 older peoplewith the lung condition idiopathic pulmonary fibrosis found the just nine doses of the drugs over three months, improved walking speed, distance and reduced frailty.
“There has never been any improvement in control groups or trials for this disease, it’s a steady downwards decline,” added Dr Kirkland.
“There was a highly significant and dramatic improvement in their physical function that you just don’t see in this condition, so that gave us enough hope to go on and now we’re doing a much bigger trial.
“We’re starting with people who wouldn’t have that much to lose if something went wrong, because this is a completely new way of treating people.
“But if we find improvements we would want to move to people with less and less serious conditions and maybe even people who have senescent cells but who don’t have the condition yet.”
The drugs used were a combination of dasatinib - usually used to treat leukemia -  and quercetin, a flavonoid found in green tea, red wine and apples. Because it takes up to six weeks for cells to become senescent, there is a large treatment window.
Dr Tamara Tchkonia, who works with Dr Kirkland added: “As an optimistic person I can say we might have these drugs in maybe two years.
“We’re at a critical juncture with the trials. There could be a lot of red lights in the tunnel but we have to start doing things differently.”
The research is also having an impact on other fields of medicine. Recently it was discovered that transplanting organs from older people into younger people raised the risk age-related disease, and scientists believe the cause was senescent cells being transferred along with the organs.
Alarmingly, zombie cells in one part of the body can also travel, so senescence in the foot could end up triggering damage in the brain.
The Mayo Clinic has now joined up with seven other research institutions across the US to form the Translational Geroscience Network, which will carry out urgent trials into the drugs.
Dr Kirkland added: “As a clinical geriatrician I got tired of prescribing better walkers wheelchairs and incontinence devices to older people.
“All of my colleagues feel the same way so for many years there has been nothing fundamental and disease modifying that we can do to alleviate frailty.
“But with a single intervention it might be possible now to affect healthspan and lifespan. Indeed that appears to be the case and that makes me hopeful.”

 

The comments are not universally bad, i.e. we'll have a population crisis, immortal politicians, etc., in short - many people seem optimistic about this.


Edited by QuestforLife, 03 April 2019 - 10:24 AM.

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#460 Fafner55

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Posted 02 December 2019 - 07:27 PM

A relationship between mortality and senescent cell accumulation I proposed in post #255 is recapitulated in this article just published.

 

“Senescent cell turnover slows with age providing an explanation for the Gompertz law” (2019) https://www.nature.c...67-019-13192-4 
 

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Also tagged with one or more of these keywords: apoptosis, scenescent cells, sasp, senolytics

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