“Better to light one small candle than to curse the darkness” - Confucius
I’m 67 y/o female & Dr Green recently changed my prescribed 100 mg of Dasatinib (accompanied by 1k Quercetin w/ea dose) to 3 days in a row every other month, while continuing to take 4 mg Sirolimus 1 x wk. Been taking Sirolimus (4mg x 1wk) & Dasatinib (100 mg x 1 mo - prior) for past 18 months. The blessing of feeling great when I started becomes a curse because I cannot state “I love my results”. My blood work consistently comes back very good. I do prioritize sleep, diet & exercise. I’m happy to be a (successful) science project in this exciting and ever changing journey!
I am familiar with these papers. Here is my quandary. It seems that every cell type has a unique SASP signature. There are around 15 or so different SASPs produced by senescent cells but those in the lung do not produce the same products as those in the skin, liver, heart, adipose tissues etc. The most reliable markers for Senescent cell count seems to be based on tissue staining, and in my clinic there is a significant resistance to poking holes in people to get tissues to stain for senescent cell count! No one is going into my liver, heart or lung for tissue Bx 2-3 times a year to see if I need another round of therapy. But we do not have a decent / reliable blood test as yet to use in making or clinical determination. Lots of smart folks are working on this, but to date no one has come up with a protocol that I think is useable. So we are still limited to clinical criteria for the moment.
And yes you are correct that young people tend to make senescent cells more slowly and clear them faster than us old farts. But even there, life style, percentage of body fat, Myokine production in those with lots of active muscle, and it’s attendant anti-senescent pro-growth bias reduces senescent cell reduction while fat, sedentary folks make them faster and clear them slower than fitter age matched people.
Metformin is also a SIRT1 inhibitor that reduces senescent cell load. Since I use both Metformin and Rapamycin, and periodic DQ therapy, all of the above is of interest to me and the Physicians in my clinics. We are also aware that maintaining youthful hormone balance has a large impact on the rate of Stem cell senescence. That is part of why we measure 8 different hormone levels in our patients 4 times a year and adjust our levels to the mid range of a healthy 25-30 year old no matter what the chronological age of the patients. We approach aging in a rather comprehensive manner compared to most clinics.
I was in the same boat until couple weeks ago that I started taking 500mg metformin just before bed and now I can proudly say “I LOVE MY RESULTS”! I wake up in the morning refreshened and feeling 20lbs lighter on my feet ( In reality I might only be a pound or so lighter). Use to take it in the morning and I was feeling shitty all day long. Thanks to guys in these forums I switched to before bed and now I’m a new man LOL
I’m not sure I understand part of your post. Feeling great is one of the goals. But why would it be a curse?
@DocJerry Excellent post and thank you for your input.
It was meant tongue in cheek. I started my protocol feeling great, so I haven’t experienced that remarkable upswing others tout in their day-to-day physical well being. I think more than anything, I’ve become more aware of the less obvious underlying issues and discovered some gut microbiome dysbiosis that would have led to future problems. With no medical background, some guidance from a couple different sources - this blog being one, I’m thoroughly intrigued and enjoying being on the forefront of this experience.
At different points in time, I’ve sporadically added Metformin throughout the week. Thanks for the reminder. I’ll add it back in and see if I can top the way I feel.
If you do add it make sure to take it before bed time. It was a big difference (for me)than when taken in the morning.
One thing you may want to consider is taking a sample to determine senescent cells in visceral adipose tissue. Based on my research, it appears that adipose tissue has the largest concentration of the most problematic senescent cells in the human body. If you measure these, you may get a good picture of the overall senescent cell load in the body. It’s also much easier to take a sample of adipose tissue than organ tissue.
Other options may be using ultrasound as senescent cells tend to clump and could show up in a scan. However, I’m not sure about this as I’ve never tested it.
@DocJerry Thanks for your valuable contribution.
A few related questions please:
- Any concerns on the well documented risk of Dasatinib on the liver and Blagosklonny’s view that it is very difficult to target l senescent cells selectively?https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416555/
- How do you feel about combining Dasatinib with Fisetin instead of Quercetin?
- What would be an appropriate age for a healthy person to consider doing a first D + Q cure?
DocJerry, That is a very interesting post. Do you mind telling what 8 hormone levels you test quarterly?
As a first approximation, however, the lowest level in a period of time of CRP gives that level of CRP which is caused by IL-6 in SASP. IL-6 may arise also from infection, but it is clear that if enough measurements are taken a background level of IL-6 can be measured via CRP.
I do blood tests weekly and can see this in my tests. They normally go up for infection one or two times a year, but then drop back to a level driven by the SASP.
Does anyone have any ideas as to why that might be?
It’s the first time I’ve seen it reported.
I always take my metformin with coffee before breakfast, so as to blunt the rise in glucose.
Oddly, taking metformin with my evening meal seems to cause some gastric distress and an acidic stomach. When I take it in the morning without food, basically the same as you, with coffee, I don’t feel any gastric problems.
Also, am not diabetic and notice no noticeable effect of metformin on my fasting blood glucose levels.
Hello Again All.
I was a bit non-paused to see the number of cogent replies and questions triggered by my posts. So here is a quick set of answers for the folks who asked.
The hormones we check every 3 months in our patients.
TSH, Free and total T3 as well as Free and total T4
Testosterone, free and total
Additionally with the q 3 month hormones we check…
Sex hormone binding globulin
High sensitivity CRP
And of course the standard CMP, CBC, Lipids, And we use our InBody device for percentage of Body fat, Muscle Mass, intracellular and extracellular water.
My physicians are scheduled for a full hour for each patient contact so we have the time to actually understand their life style issues and help them do problem solving for the things impeding their program.
As I said earlier, we have a bit more of a comprehensive program than most of our fellow physicians.
As for the question regarding the risks of dasatinib on liver, the drug is normally used daily for years at a time. In that setting liver and cardiac risks are indeed of some concern. But for a 3 day course followed by a 4 day wash out, our experience is very benign. Personally I get a bit headachy and out of sorts on the 3rd day but it clears totally the following morning. I do have one of our doctors who had a painful swelling of her cheeks with a single dose. But that seems to be an idiosyncratic reaction that we have not seen in anyone else. One of our 85 year olds had an upset stomach with each dose even when taken with food, but he tolerated a 50mg dose for 5 days well instead of the 3 day 100mg dose.
Fisetin vs Quercetin. I started with Q years ago when the Mayo published their first papers and have simply had no reason to switch from something that works well. I have no objection to a D/F program but am not aware of peer reviewed papers of the combination.
I have not used it in anyone under 50 thus far. Until I get a well documented SASP based protocol that will let me objectively evaluate their Senescent load, I am not pushing the age range for now. (OK I just realized that is not quite true. My wife who is only 47 started periodic therapy 2 years ago with a bit lighter, set of 2, 3day courses of D/Q twice a year. but I have not used it in a patient under 50.)
I hope this provides some basic guidance for someone.
Really helpful and informative! Many thanks!
Thanks I will try this for starters