What did you decide for dosing? I’m considering trying a few cycles but have no idea how much I will need to purchase.
I’ve seen dosing range from;
3x 25mg doses in 5 days - i.e. on-off-on-off-on then cycle again in 6 or 12 months
6x 3mg doses in 11 days
6x 1mg doses in 11 days
Each one of those cycles is 1 day on, 1 day off until the cycle is completed. And do that once or twice per year.
I’ve settled on the 6x 3mg (18mg total) in 11 days for my first experiment. Will be doing that in Jan as I’m finishing up our TA-1 experiment the end of December.
Thanks for the prompt response. When 10mg is $300, I’m not sure if I can afford multiple cycles.
These results support the relevance of SASP proteins to human aging, identify specific traits that are potentially affected by SASP, and prioritize specific SASP proteins for their utility as biomarkers of human aging.
Proteomic Analysis of the Senescence-Associated Secretory Phenotype: GDF-15, IGFBP-2, and Cystatin-C Are Associated With Multiple Aging Traits | The Journals of Gerontology: Series A | Oxford Academic?
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Senolytic therapy preserves blood-brain barrier integrity and promotes microglia homeostasis in a tauopathy model
https://www.sciencedirect.com/science/article/pii/S0969996124003127?via%3Dihub
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IMO: The best senolytic therapy is rapamycin or the DAV protocol.
Try reading the DAV Therapy thread. Detailed information is given about the protocol.
“My DAV* Therapy Experiment begins! *Doxycycline, Azithromycin and Vitamin C”
The ingredients are available from India for a reasonable price, if you are able to receive exports from India.
The therapy uses Azithromycin + Doxycycline + Vitamin C.
"The present approach effectively eradicates senescent cells and cells carrying the hallmarks associated with aging.
I have tried the protocol twice. Did I notice any subjective effects? No…
These have been posted before:
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Do you cycle between DAV and Rapa or favor one approach over the other?
I have used both. Currently, I am on vacation from rapamycin. I plan on starting rapamycin again next year. I have tried the DAV protocol twice, and there are no subjective results.
I am unaware of any practical, affordable, available cell senescence tests, so you have to take a leap of faith when using these protocols to reduce cell senescence.
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I feel like much of what we do is a leap of faith as the placebo effect is hard to objectify. But as most of us are already in very good or perfect health, it’s difficult to see many changes without specific and expensive testing.
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Senescence is a 2 edged sword, some is beneficial but the nature of an “immortal” cells type that is hard to clear out, especially as the immune system declines causes significant increase in inflammatory response that no amount of “lifestyle” can fix.
2.4. Senescence-Associated Secretory Phenotype (SASP)
Cells may enter a senescent state as a consequence of various stressors, which further drives organismal aging. Cell cycle arrest is a typical feature of cellular aging; it leads to a stable, terminal proliferative halt and the development of a SASP [54]. The SASP defines the secretion of various cytokines, chemokines, growth factors, proteases, and lipids by senescent cells. This concept was first introduced by Krtolica et al. in 2001 [55]; they proposed that senescent cells secrete factors into their microenvironment, thereby potentially modulating biological activities both locally and systemically. In 2008, the SASP, also known as the senescence-messaging secretome, was independently characterized by various laboratories as primarily consisting of pro-inflammatory and growth-stimulating proteins [56,57]. This secretion leads to chronic inflammation and tissue damage in organisms. The composition of the secretome varies depending on the trigger of senescence, and the proportion of senescent cells in very old primates is estimated to range from 5 to 20% [58], contributing to age-related diseases. The SASP can also interact with immune cells, creating feedback loops that exacerbate tissue damage
[44].
Immune Alterations with Aging: Mechanisms and Intervention Strategies
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I’m going to do a full writeup on this - SapereX was at the conference this week and they have a test that I think retails for $650 for measuring P16 levels in the body. Its a test that is only starting to become available and only via certain longevity doctors (mostly in major cities) - so not available for most people, but it looks interesting.
More info on SapereX and the research they are based on: https://www.saperex.com/copy-of-early-access
I’m doing a full report on this company/test in the near future with details, and we can discuss the pros and cons of this approach. I believe that this is the first commercially available scenescent cell load blood test that is becoming available, and doctors are using it as a metric to test to determine whether to prescribe senolytics (high dose fisetin and quercetin) and / or rapamycin.
and they are doing pre/post testing to show how these therapeutic approaches impact the senescent cell levels in the body:
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This is an important test, hope it is as relevant as it appears to be.
@DrFraser will you have access to this test?
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I can get access as a longevity medicine physician, I’d guess. Will need to see the details on how it needs to be drawn and how delivered to their lab (e.g. packed in dry ice), timing of draw until it needs to get to their lab.
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Yes - the doctor needs to do a blood draw, and the blood sample (about 8ml they tell me) has to be shipped by FedEx with dry ice. SapereX has a prep package for the blood that they send to their associated doctors. That is one of the factors that drives up the cost, unfortunately.
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I’d need to get the details, but I’m not convinced that one couldn’t get the blood draw by a phlebotomist and send it in. I’ll have to contact them if there is interest on the forum and I’m happy ordering this for individuals if there was a system setup to allow a sensible pattern of community collection. There is nothing magical by having me draw the blood - the phlebotomist can do the same thing.
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Is there an explanation as to how senescence in other tissue cells can be picked up in the blood?
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This is a fairly long article with lots of reference material for anyone interested. For about 3 years I read 2 to 3 studies on senescence every day. Well maybe not every day but I have bookmarked over 200 that I’ve read 
and I’m convinced that as indicated in more than 1 study and in articles on the 12 Hallmarks of Aging where senescence is identified as the #1 issue to resolve for living a more more disease free life.
In the mean time I’ll be doing a cycle of FOXO4-DRI in Jan
To advance, we must have clear and ideally distinct single or combinations of markers for senescence that would identify whether it is skewed to a detrimental or beneficial response clinically. Significant resources are being placed in this area, such as in the creation of The National Institutes of Health (NIH) Cellular Senescence Network (SenNet) Consortium (SenNetT)187. SenNet aims to map senescent cells using single-cell technologies across mouse and human lifespans in multiple tissues
Emerging insights in senescence: pathways from preclinical models to therapeutic innovations
https://www.nature.com/articles/s41514-024-00181-1
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The field needs to try to.answer the question as to where most senescent cells come from. I dont think it is replicative senescence. Instead it is the failure to differentiate.
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The hidden role of senescent cells in ageing and organ dysfunction
The study introduces a “senescence atlas” mapping the distribution of these cells
This study showed that the senescence of immune cells could affect the phenotypical change of the parenchymal cells in the elderly and suggests that targeting immunosenescence might be a strategy to control functional decline in this population.
https://www.nature.com/articles/s12276-024-01354-4
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The immune system can distribute mitochondria.
