"Senolytic Activator" and Extended Fasting …

Suzanne I think nobody knows the answer to that, we'd have to do a direct clinical trial on both. LE might have an estimate though, I've found if you send them a product query they're excellent at replying with what they think. Carefully worded of course. 

FWIW, on the one hand plants are basically chemical factories, and most or many drugs come from distilled plants. Dr Peter Attila said when his patents tell him they'd rather have a more 'natural' approach via supplementation he asks why, when supplements are basically unregulated drugs? So in theory it could be as or more effective. 

On the other hand the only work here is LE went through a database of parameters from plants and found a combination believed to be similar. So again no idea. 

My approach is that the LE activator is cheap and easy so I'll give it a shot. The problem is none of us have any measure for senolytic activity, except possibly our hair might lose some grey. For that reason as part of my daily biometric I take a mug shot. 

Iðunn Agree with your point here. Once you have the digestive tract interfering most (or many at least) compounds fail to have the same effect as they do when isolated. I got the Senolytic activator as a 'why not because it's cheap' experiment but probably won't continue it. 

Otherwise I'm approaching my Winter solstice fast, probably a low key one this year of 4 days. I'm not planning on taking any supplements during it. 

albedo Great thoughts. Unfortunately I don't think these tests will tell us specifically if senescent cells are being mitigated. 

The calculators are population referenced, meaning that the markers fit models created models created from age specified input variables. Roughly this means that if your numbers look rather like those from some age bracket then you get that result. 

On the physical DNAm test we don't get help either. I'm using myDNAage.com , which uses a method developed by Dr Steve Horvath. Horvath is a statistician, he simply ran an analysis of age versus various epigenetic markers, and took the ones most correlated. But if you look further into the method, while researchers are tremendously excited about it due to its accuracy in 'predicting' age (or better said maybe, correlating age) nobody knows why it works this way. We certainly don' know if it corresponds to senescent cells. 

And finally, the really important question is does the calculated/measured biological age actually correspond to remaining lifespan? Simple example, suppose for a minute that NAD levels don't reflect in any of these tests, and suppose that a NAD level of zero does result in death, then these are only partial estimators. 

albedo We don't have causality, without that all we have is different variables conflating with each other and can't say a-priori that it's senescence specifically. Taking a step back, it doesn't really matter. If whatever we do drives our aging markers down then that's success, we can leave it to the lab rats to figure out what variable (senescence, mitochondria function, etc) was improved. 

I think we're in agreement though. What I worry about sometimes is what important factors are being missed? For example, a person could have great biomarkers, be doing NAD, senolytics, etc, yet still have the apoe4 gene and develop dementia/alzheimer's in late life. Or just memory loss, or something else. We have a lot of systems that need to be kept running. Longevity escape velocity might be reached in a decade, but surely not for everything right away. 

albedo Yeah that young.ai site has coming all sorts of markers - pictures (work has been done by networks figuring age from a face photo), oh I forget but a bunch of stuff. I think these guys are on the right track, actual bio age should come from every marker we have (100+), including ones you might not think of. For example, the soles of your feet. Soles have a tissue that degrades over a lifetime of walking, this is why when we get old we tend to get plantar fasciitis and other feed ailments. I think this falls into Aubreys "cellular matrix' category. I started to get this, and some fancy expensive custom orthotics fixed the problem thankfully. But my feet are not the same as they were when I was 20. So even though I might have good blood markers, I should get dinged because of the age of my feet.

adonoho said:
As a result, I think we see "diseases", such as senolytic cell accumulation, that our body could not afford to tolerate in earlier ages. Senolytic cells are a bug in the program; cells that should have died but didn't

 Yeah that's a hot topic of discussion. One the one side you have the evolutionists, who say aging is caused by DNA programming (somehow) or lack of DNA programming. On the other side you have the accumulated damage theory. I believe the latter theory appears to be winning. Something complicating the programming theory of senescent cells is that they actually provide a pro-immunity function later in life. So they do 'poison' the cells around them, but with aging elders who have impaired immune function, those same senescent cells become active during infection in a positive way. My takeaway from this is that as you age you want both low senescence and high immune function, thus not needing the senescent cells. As you say, periodic true fasting addresses both by recycling the senescent cells, and improving immune by recycling old T-cells, plus all the other bennies. 

My wife has a hard time fasting, at least on her recent first one (first time is always the hardest). I'll put her on the LE activator and I'll discontinue it for myself. On Rapa I'm going back and forth, I have a aging management Dr who will probably prescribe it for me, but I'm waiting for more data on that front. Springtime in the earliest. 

adonoho Yes we practice time restricted feeding, thanks. FWIW I don't support the ketogenic diet approach, it seems clear to me that intermittent ketosis via periodic fasting works, but chronic ketosis is in the cateogry of a 'good thing taken too far'. Our bodies are designed to run on glucose, you need to alternate rest/repair with stress, and so alternating ketosis was normal feeding appears (to me at least) to be the right approach. This is the same pattern we se with exercise, an optimal approach is to alternate rest with exercise stress. 

I had several stints at the True North Health Center where they've had tens of thousands of patients do medically supervised fasts. They're pretty much the experts AFAIK, their take is that fasting is just hard any way you take it. The head of the group, Dr Goldhammer, told me he does yearly maintenance fasts and still doesn't like it :)

adonoho I think we also agree here. Taking your Type 2 example, yes it's both genetic and lifestyle. I have several defects for high fasting glucose, which by my 20's resulted in terrible health and blood work. Back then I addressed it purely by lifestyle, which led to me being such a health fanatic. I did fix the problem, but now in my 50's my glucose is creeping up again, despite all the work I'm doing! So now I'm on Metformin, plus daily intense aerobic exercise in the morning. The two are successfully managing the issue. This demonstrates your point I think, that there's a intersection between genetics (the coding) and epigenetics (lifestyle). 

BobM Senescent cells are recycled, your body literally reuses the golgi and other parts. The only way to measure senescence that I know is by taking a tissue sample and using dye to visually see the senescent cells in a microscope. This highlights the fasting mechanism; in the absence of energy (glucose) your body is both in a anabolic state (not catabolic digestion - sometimes I get these backwards) which is a repair state. Secondly, your body is looking for energy. So it goes on a shopping trip in your system. It clears out plaques from your arteries, clears out senescent cells, old T-cells and so forth. These are all recycled and turned into food. You literally start eating yourself, but your body is smart and is protein sparing. It does everything to preserve the heart and brain first, then muscles, so it goes after the baggage (old junk and fat stores). 

 Well there might be one test, I don't know if anybody has looked at this (note I'm a physicist/engineer/musician/composer, not a biologist!) which is using the Ames test for broken DNA in the urine. I believe this is mainly used for mitochondrial function (since DNA repair (mostly?) occurs there), but I wouldn't be surprised to find that increasing senescent cells also increase broken DNA. OTOH that might be sufficiently mitigated by immune and mitochondrial function. 

The DNAage test I took looks at methylation, not discarded broken DNA AFAIK. Your body can't recycle DNA apparently so just excretes it. n.b., except digestive DNA? I recall there's a step in digestion, after the stomach, where <something> pulls out all the foreign DNA in your food that made it through the hydrochloric acid in the stomach. I don't know what happens with that DNA, whether it's used or discarded.