Senescence is IMO caused in the main by differentiation problems. Although mitochondrial efficiency is part of this the shortage of acetyl-CoA as a result of IL-10 effects is perhaps the most important driver in the long term.
I thought it was the plaque buildup itself which caused inflammation in the endothelial cell lining? Maybe I have misunderstood. However, it’s the inflammation which is targeted by low dose Colchicine which is why the FDA recently approved it to be used immediately after certain CV events.
are there scientific papers to support this? “Exercise clears out senescent cells”
Lots. For example,
If Arterial Plaque is in part caused by epithelial cells not differentiating properly and becoming senescent (which I personally think is part of the cause as well as Lipid issues) then reducing senescence should remove arterial placque. The main issue with this might be how quickly this happens.
What has not really been clarified is what causes senescence. I think a lot of it is failed differentiation of stem cells.
Senescent endothelial cells and vascular smooth muscle cells are found in atherosclerotic plaque, and studies indicate that these cells are involved in progression of plaque.
Mummies reveal that clogged arteries plagued the ancient world
Scans suggest that there’s more to heart disease than a modern diet.
Clogged arteries are seen as the quintessential symptom of an unhealthy modern lifestyle. But the condition was common across the ancient world, even among active hunter–gatherers with no access to junk food, a study of mummies has found.
“There’s a belief that if we go back in time, everything’s going to be OK,” says cardiologist Greg Thomas of the University of California, Irvine, a senior member of the study team. “But these mummies still have coronary artery disease.” The paper is published in the current issue of The Lancet1.
“Most ancient Egyptians ate two meals a day: a morning meal of bread and beer, followed by a hearty dinner with vegetables, meat – and more bread and beer.”
For heart disease, you need a relatively high level of lipids plus inflammation. If the inflammation causing arteriosclerosis is caused by senescent cells, then a two pronged approach to fighting heart disease is warranted.
- Reduce LDL and ApoB
- Reduce senescent cells
The best way to do #2 is through senomorphics such as Rapamycin and Taurine.
Senolytics are effective as well, but not as effective as senomorphics that prevent senescence in the first place.
My view on senomorphics like citrate is that they can take senescent cells and get them functionally in the main cell cycle (that’s my experience).
Mybe occasional dasatinibe + quercetin too ?
Quercetin is an HDAC inhibitor. Personally I go for taking Quercetin combined with a number of HDAC inhibitors as well as Citrate, B6 and B9/12.
take it with fat? as it would be more soluble?
Came across a new paper on citrate transporters and I thought of your comments.
This article is much too technical for me and I don’t pretend to understand it. But, it is open source and complete.
“The citrate transporters SLC13A5 and SLC25A1
elicit different metabolic responses and phenotypes
in the mouse”
There are issues with this paper i have raised with the author, but the experimental results are helpful even if the analysis is flawed.
I’ve been doing D&Q for a few months. Feel fantastic (used to get headaches the day after - I’m on once a fortnight as per ITP protocol) now the only way to describe it (and this might be psychosomatic) is cleaned out. Like I’ve flushed my body of all the senescenct filth
Stress can cause heart disease. I imagine the life of an ancient hunter-gatherer was not without stress, even though they weren’t fighting traffic on the way to the office every day.
Stress is an underrated killer. Without even looking up any literature on the subject, I can tell you some of the things that I have observed.
It kills sleep
It causes depression
It raises blood pressure
It causes stress eating in many people. Stress eating is caused by people using food they like for comfort. This I have seen so many times at work, but seldom see this issue addressed.
Yeah, nothing better when the most random problem pops out of nowhere than to eat a large plate of unhealthy food, or other similar behavior…
It’s not suprising people are ‘unhealthy’ with how everything seems like it’s falling apart. It’s important to keep perspective and not stress over the small stuff (relative to other possible or actual bigger stuff, it’s small).
Just a stroll through the forest doesn’t sound too bad, we do that nowadays for recreation. But the parasitic infections, plague, violence, and infant mortality would suck.
To say nothing of the constant threat of starvation (though I guess the caloric restriction may have been helpful).
Most recent paper from the Japanese authors of the initial study published today:
Aging is a major risk factor for cardiovascular diseases (CVDs) and accumulating evidence indicates that biological aging has a significant effect on the onset and progression of CVDs. In recent years, therapies targeting senescent cells (senotherapies), particularly senolytics that selectively eliminate senescent cells, have been developed and show promise for treating geriatric syndromes and age-associated diseases, including CVDs. In 2 pilot studies published in 2019 the senolytic combination, dasatinib plus quercetin, improved physical function in patients with idiopathic pulmonary fibrosis and eliminated senescent cells from adipose tissue in patients with diabetic kidney disease. More than 30 clinical trials using senolytics are currently underway or planned. In preclinical CVD models, senolytics appear to improve heart failure, ischemic heart disease, valvular heart disease, atherosclerosis, aortic aneurysm, vascular dysfunction, dialysis arteriovenous fistula patency, and pre-eclampsia. Because senotherapies are completely different strategies from existing treatment paradigms, they might alleviate diseases for which there are no current effective treatments or they could be used in addition to current therapies to enhance efficacy. Moreover, senotherapies might delay, prevent, alleviate or treat multiple diseases in the elderly and reduce polypharmacy, because senotherapies target fundamental aging mechanisms. We comprehensively summarize the preclinical evidence about senotherapies for CVDs and discuss future prospects for their clinical application.
For those who have not seen, review