Apparently taking low-dose lithium is a senolytic, according to the YouTube video posted by @DeStrider.
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Utilizing the fact that SASP is unique to the senescent cell type, being able to measure specific secretions as a bio-marker may be an excellent indicator for potential and emerging health issues.
Further characterization of senescent cells from diverse cell types that include cells of the brain (neurons, astrocytes, glia, oligodendrocytes) and their secretomes may be helpful in generating senotype-specific (senescent cell subtype-specific) signatures with greater sensitivity and specificity to MCI and related outcomes
Plasma senescence associated secretory proteins: A new link to mild cognitive impairment
Similarly, elevated senescent cells has been observed among excitatory neurons in the brain of subjects with Alzheimer’s disease (AD) showing greater accumulation of neurofibrillary tangles, suggesting that the senescent cells might play a role in the progression of AD.
In the study by Mielke et al., the authors have explored this possibility by analyzing the plasma levels of certain SASP markers to predict risk of mild cognitive impairment (MCI) among older adults
https://www.sciencedirect.com/science/article/pii/S1279770725000855?via%3Dihub
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Great picture of artichokes? Which are a poor source of apigenin. Best source is dried parsley.
They mention Rutin which I take and believe in as doing the same thing.
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This is very incorrect. There is a reason they are there in the first place. They do have a purpose.
Ofcourse they have. Learn dr. Green’s articles about this purpose, based on Dawkins and Blagosklonny works.
Senescent cells do have a purpose to kill you to free some space for the next generations. Its evolutionary purpose designed by “selfish gene”.
This is the basic not-understanding of aging and evolution by a lot of scientists, Dr. Alan spoke about so much.
So every person, who starts these talks about “beneficial purposes of senescent cells” and other bs, based on misconception of “everything what nature done is evolutionarely good fo HIMSELF” are wrong. Cause nature done good for SPECIES, not for individuals. Aging and death included.
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No, hey are not designed to kill you to make space for the next generations. That is misleading. Evolution selects for reproductive success. Cellular senescence has some benefits early in life, like for wound healing and protecting against cancer. This is an good example of antagonistic pleitropy and decreased maintenance later in life when selection pressure is low.
Dr. Alan is not up to date on senescent cells. He is dead. Initially when senescent cells got attention in the longevity space they were thought to be almost entirely harmful but later studies showed that they do have benefits also for the individuals. Biology is usually not black and white. Things are almost always more complicated than they seem at first.
This reverses how evolution works. Natural selection acts on tratis that increase reproductive success of individuals, not what is good for the species. When some trait is beneficial for other members of the species, that’s a secondary effect derived from benefits for relatives.
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So how often would that 9 day cycle happen?
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He is dead but he was smart.
You can argue with me, but please do not be arrogant and disrespectful to the people, who were truly inspirations and pioneers in the field of ultimate fight with diseases for all human kind. Thank you in advance.
Your vision of “how evolution works” is miles from truth - and to the opposite direction. (Its only my opinion, ofcourse). You can read “The Selfish Gene” of Dawkings, maybe it will enlighten you. Or Michail Blagosklonny’s articles.
Even species are not “the central subjects” of evolution.
Some info to think about - go and tell mantises how evolution works for individual’s benefits.
Until Yamanaka’s factors will be tuned to the point of using for humans, we have to get rid of SC. Trying to slow conversion to this state of proliferating cells, and removing cells, which, despite our efforts, has become SCs. They are programmed poison.
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I had joint pain in the left wrist, leaned awkwardly. Had to used sticky stripes, even a splint couple of times. Its eased the pain but never made it to go away completely. After one 3-days session of Q+F (3g each) with some additional (herbal) substances (most notably, piperin and a lot of olive oil) it went away in a week.
Maybe a coincidence. You never know when experimenting with yourself.
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"The evidence that senescence is heterogeneous in nature, as with many biological processes, is clear. However, due to the extensive literature describing senescence ablation leading to relevant improvements in treating many age-related disorders, heterogeneity does not inherently limit the potential therapeutic benefit of modulating senescent cells in vivo. Rather, it underpins the need for further characterisation of this will contribute to the development of more effective senotherapies with increased specificity and sensitivity."
He was definitely very smart and I highly respect his contributions to science. However, I don’t think it’s disrespectful to acknowledge that even the smartest of people are still wrong about a lot of things. Nobody is above criticism and there is no shame in not being up to date on everything. Note that I’m not attacking his character. I’m attacking the logic behind thinking that senescent cells are purely bad and that evolution selects for species survival rather than individual gene propagation. If you want to convince me of something, convince me with sound arguments, not with “x said this”.
I don’t like your condenscenting tone here. I think you may have misunderstood the book. Dawkins main claim is that evolution is centered around gene selection not species selection. It supports my position. I invite you to ask ChatGPT if you don’t believe me.
I am a big fan of Blagoskloonny and I have been reading his articles for 15 years, just FYI.
This is wrong, and the mantis example is irrelevant.
This shows limited understanding of human biology. It’s becoming well established that senescent cells are not purely harmful but instead they have pros and cons. Getting rid of them completely can cause harm in some ways while being beneficial in others. Also reprogramming with Yamanaka factors is not an ultimate solution to aging like many people believe. It’s one part of the solution but not enough alone.
This is an overly simplistic view of senescent cells. I say that as someone that has read a lot of studies on senescent cells, not just read about what other people say about them.
I am in full agreement with the above quote. It doesn’t contradict anything I said. Note that I never said that we shouldn’t get rid of any senescent cells, only that they are not purely harmful. Therefore, the solution is not to simply get rid of them all but optimally to get rid of the right ones at the right time in the right places, while leaving a lot of them intact, where they provide more benefit than harm. As an example, you do want a certain amount of senescent cells around wounds, or else wound healing will be suboptimal. That’s just one example of where they might be beneficial.
The problem with current senolytic therapies is that they are a shotgun approach. They kill them indiscriminately and make no distinction between senescent cells that cause more harm than good and those that do more good than harm. They can still be beneficial in certain contexts but they are far from optimal.
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Looks like “well-weightened position”. But only looks.
- A car, which hit you dead, also has a lot of good options, intents, and useful applications. Senescent cells may have some beneficial options. It doesn’t matter if they age a human, because it ends with death.
- You can’t just ignore mantis and go further. This is just a small example of the counterargument to your position (one of many). Evolution can be deadly to individual. Because its beneficial for a gene. So you are wrong. If someone wrong in his premise, its not necessary to observe his conclusions - they are false by logic. The mechanism of senescence driven by mTOR may be invented by evolution exactly to kill the host. No benefits included. All this “wound-healing help” can be resolve somehow with other mechanisms. Aging - only by removing SCs (doesn’t matter how - quieting, killing, reprogramming to be prolifirative again).
- Solution for today is exactly to simply get rid of them. Because your “looks-like-wise” position to “carefully mesure better options” and “leaving some of SCs around wounds” and " make distinction between SCs" are fictional. Today there are no such mechanisms and technologies. Period.
Maybe they will appear, someday. Even - for sure, they will. And everyone will be informed (being 76yo) that you have to start this hi-end therapy (cost like an aircraft, ofcourse) from your adolescence. Absolutely like this nonsense with Omega-3 study from 2018, where eggheads told us that Vit-D and Omega-3 for 5 years - are no more than a placebo. Ofcourse its a placebo if you take it for the puny 5 years! Omega mimics fish-consuming. So if you want same results as Okinawian guys - you must eat this Omega-3 like they ate fish - from your birth. And way more than 1g per day.
So, now all we have is 4 approved affordable and obtainable senolitics and several senomorphics plus The Great Rapamycin which is still not approved for anti-aging purposes - with absolutely identical objections to your’s, from the guys with the same overcaution mentality.
Should we spend time on waiting?
- Your objections are not scientific, because they are against Popper’s criteria of scientific. Falsifiability. Exactly the same you can say about every medical drug and medical intervention in human history. Word for word. “Its not ideally and specifically acting on the matter. It needs future research. It can cause complications we still don’t know about”.
Of course it will! Every drug in this world will cause complications doctors didn’t knew about when they started therapies for the 1st time. Based on this criteria of “not starting” - no medication had started ever.
You are right in one crucial thing - we don’t have to dive into every “snake oil” thing mindlessly. We must weight our options for sure. But using senolytics from the arsenal we already have, intermittently, inside the already studied dosages - we can also for sure. With all precautions, ofcourse.
Anyway - peace!)
I don’t think it’s productive to continue this discussion.
You’re largely talking past my claims and attributing positions to me that I have not made and responding with analogies rather than directly addressing the points I made.
I’m not arguing for avoidiing senolytics or not taking action now. I’m arguing that senescence is complicated, and that a shotgun approach has benefits and costs that need to be weighted. Saying “we must act now” doesn’t address that. I take plenty of action now to live longer and healthier, but I weight the pros and cons of each of them.
Given your tone and misinterpretation of my positions, I don’t see a good reason to continue this discussion. So I’ll leave it at that. Have a nice day.
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Too many senescent cells are not beneficial. This is why I try to adhere to the theory of maintaining a Threshold of Senescence.
The biggest problem is knowing how much of your system is being affected by excess senescent cells and how to keep that under control. We need a cost effective test for this.
Since viral and bacterial infections do impair the immune system, this sub-optimal immune system allowis SNC’s to hang around longer (immortal cells will do that), allowing SASP to increase significantly.
Covid significantly increases SNC’s in the lungs. Without clearing them, our lungs become impaired as long as those SNC’s are present.
both ME/CFS and long COVID are fundamentally driven and chronically maintained by PERSISTENT ENDOTHELIAL CELL SENESCENCE, triggered, by acute viral infection and prolonged by IMMUNE DYSFUNCTION, which causes multisystem inflammation, impaired tissue perfusion (especially in the brain), and the full spectrum of devastating symptoms including PEM and profound fatigue.
Virus-induced endothelial senescence as a cause and driving factor for ME/CFS and long COVID: mediated by a dysfunctional immune system.
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Another interesting result in Mice with FOX04-DRI
This was using the “typical” dose in mice that translates into what is typically used in humans in studies - Using standard body surface area conversion, the human‑equivalent dose (HED) of 5 mg/kg FOXO4‑DRI in mice is ≈0.4 mg/kg in humans.
Calculation (mouse → human)
- Mouse Km factor ≈ 3; human adult Km factor ≈ 37.
- HED (mg/kg) = Animal dose (mg/kg) × (Km_mouse / Km_human).
- HED ≈ 5 × (3 ÷ 37) ≈ 0.41 mg/kg (commonly rounded to 0.4 mg/kg).
FOXO4-DRI regulates endothelial cell senescence via the P53 signaling pathway
Results: Injection of FOXO4-DRI in both naturally aged and induced aging mice effectively suppressed aortic aging and improved aortic function. Additionally, we found that FOXO4-DRI alleviates endothelial cell senescence induced by OGD, thereby enhancing endothelial cell function. Through co-immunoprecipitation (CO-IP) experiments, we discovered that FOXO4-DRI prevents the binding of FOXO4 to P53, facilitating the phosphorylated P53 nuclear exclusion, which subsequently trigger BAX and cleaved caspase-3, leading to the apoptosis of senescent cells. Ultimately, this mechanism achieves the goal of inhibiting vascular aging.
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Paper that evaluates various senolytics for efficacy, using some kind of specificity index. This seems like a Decdnt framework to evaluate these substances, or at least a good start.
The other interesting part is that they did find that senolytics didn’t completely clean up senescent cells, and that in some cases a senomorphic like Sglt2 inhibitor could help.
even upon extended treatment with these most potent senolytics, a proportion of senescent cells remained viable. We found that senolytic resistance was driven by maintenance of mitochondrial integrity through V-ATPase-mediated clearance of damaged mitochondria. Imposing mitochondrial stress via metabolic workload enhanced the senolytic efficacies of ABT263 and ARV825 in vitro, and in mouse models, ketogenic diet adoption or SGLT2 inhibition similarly potentiated ABT263-induced and ARV825-induced senolysis, reducing metastasis and tumor growth. These findings suggest that mitochondrial quality control is a key determinant of resistance to ABT263-induced and ARV825-induced senolysis, providing a possible framework for rational combination senotherapies.
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I tried senolytics for a while and it didn’t move the needle. Probably because I didn’t have enough senescent cells. I do think that they could be useful if you have a high load of senescent cells. If not, stick to senomorphics for prevention.
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