Here is my senescence therapy. It uses three techniques to maximize senescence. As others have done, perhaps more than just fisetin is needed to be successful.
The ‘plan’ was to start #1 and #2 on the first day, get the body to activate cell-cycle arrest and apoptosis so as to in the best state for the senolytics. Then three senolytics on days two through four. Finally, two days of rest with no supplements, then 4 days of NAD+ rejuvenation therapy.
The protocol was conceived with three calorie restricted meal times - AM, PM and noon. Noon is a large plain salad with a bit of oil and vinegar dressing and water for beverage. AM and PM are the supplement fortified drink made from a base and an activate mix & liquids. The base is protein, fiber for bulk, and as a tasty vehicle for the activate mix. It’s a few hundred calories. Activate molecules aim for p53 and p21 expression. Beyond that, there are some calories in the oils and emulsions. I premade enough of the two dry mixes for ease of use.
I felt p53 and p21 were important factors that need to be optimized to improve senescence outcome.
“The p53 protein is a key tumor-suppressor protein at the crossroads of cellular stress response pathways. Through these pathways, which can lead to cell-cycle arrest, DNA repair, cellular senescence, differentiation or apoptosis, p53 facilitates the repair and survival of damaged cells or the elimination of severely damaged cells from the replicative pool to protect the organism”
“We suggest that p53 and p21Cip1 have dual roles in the regulation of growth arrest and DNA synthesis in primary rat hepatocytes.”
https://www.nature.com/articles/1210937
- BASE (Dry Mix) - Fiber (psyllium), Protein Powder Mix (Veggie/Casein/Whey/Goat), Cocoa, Coconut sugar (low-glycemic)
- ACTIVATE p53 & p21 ( 5g /day Dry Mix) - Vitamin C, Reishi, Watercress Extract, Purple Fruit & Veggie Extract, Ashwagandha, Bromelain, Betaine HCL, Pepsin, Zinc, Ginger, Vitamin D
- ACTIVATE P53 & p21 (Liquid) - Black Seed Oil (Thymoquinone), Resveratrol, Curcumin, Tocotrienols, Sunflower Lecithin (emulsifier)
- SENOLYTICS - Fisetin (1g/day), Piper Longum (2g/day), Quercetin (300 mgs/day sublingual)
Although I’ve not posted them here, I cataloged references and reasoning for all supplements included.
Before beginning this protocol, I stopped all supplements two days prior, then started the protocol in the evening.
12/26/18 Wednesday
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6pm 1st dose of mix, less Quercetin, Fisetin, Piper Longum, R&C. Taste is just ok, think black seed oil tastes odd.
12/27/18 Thursday
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6am No hunger from last night. Weight down 1.4 lbs to 148. Did same stuff but added missing R&C. Taste is same, ok. Tired took a nap.
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12pm Lunch of salad and oil dressing approx 150 calories. Did 3.4 mile walk prior fine. Little tired but not hungry! Also had 20 grapes as desert. Also note that the protein smoothie and oils used each dose are approx 300 cal/dose.
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6pm 1st dose mix with fisetin 700 mg. Little too strong, took 90% only. Felt bit odd, and hungry, so ate salad bowl.
12/28/18 Friday
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6am Used leftover and 400 mg new fisetin in dose. Quercetin taken separate sublingual. No problem with dose now. Feel full and only a bit strange. Lost 3 lbs since start. Did add little more cocoa and veggie powder to equal 40 grams. Taking quercetin separately as sublingual. Tired took a nap.
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12pm Lunch of lrg salad, oil dressing. Feeling odd like IF, but ok. Tired took a nap.
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6pm Settled on 500 mgs fisetin. Made new mix with modified amts of ingredients. Party in PM had water and tiny bit pulled pork, scalloped potato, deviled eggs.
12/29/18 Saturday
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7am Routine dosing. Think eating a bit last night made me feel better.
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Lunch - Extra large salad, plus popcorn. Went for walk of three miles, quite tired, bit dizzy, send heart beating.
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6pm Routine dosing, plus popcorn and a piece of cheese and some tuna fish.
12/30/18 Sunday
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Stopped protocol. Felt I’ve had enough, I don’t like the energyless feeling I have - simply my gut feel. I want my ‘good body, strong body,’ feeling back.
End result totals: Fisetin ~2.6g, Piper Longum ~10g, Quercetin ~1.5g
> I will repeat this in one month with less calorie restriction. Likely I’ll eat a small meal of limited calories AM and PM and keep the salad at noon.
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I didn’t follow through on the last parts of the protocol, that is, the two days rest and then the recover regimen. I felt strange enough that I just wanted to feel normal. So I did the recover regimen straight away. It worked.
The recovery regimen consists of NMN (sublingual), PeakATP, Quercetin, low dose Melatonin, and a low dose multivitamin (most components less than the MDR) for two days. After that, I resumed my normal supplements.
I wouldn’t say I felt great doing this protocol, I had a definite ‘odd-out of sorts’ body sense. Perhaps I’m not accustomed to how CR feels? Whatever, I regained my sense of feeling normal by going back to my usual daily protocol (and food)!
As to did this work, well I look at things a bit different from, say, some current study metrics of improvement in the elderly. I think one study was judging improvement on Improved gait speed on a 6 minute walk. Myself, I look at how well my body performs doing more substantial effort. I wish studies would more focus on able body adults and elders rather than on the weakest among us. After all, improved lifespan is a most important aspect of everyone's life, not only the weak and ill.
For example, see the attached graph below of how my cardiovascular system functioned during a 28 mile bike ride earlier today. I’m quite pleased it took some 5 miles to get my HR to ‘working speed’, and from there on out it just did it’s job without complaint.
I’ve noticed a couple things different cycling since the treatment. At the average HR of ~137 bpm, my breathing rate seems slower, just steady deep breathing. Also my HR seems to be easily going towards 160 bpm and in spikes beyond for short periods, with no distress. I just slow a bit to slow it down, no sense pushing it. The weird thing also is a don’t feel any cardiovascular strain, my body just works, perhaps better than it ever has.
Whether this has anything at all to do with what I did for a few days with this protocol is certainly an open question.
If cellular senescence helps with healthspan parameters I track, I’m all in. I want to stay fit into my 70s, 80s and beyond. Alternatively, If all such a therapy can do is help someone push their walker a bit faster for a few feet, it’s not sure it’s worth the effort. Time will hopefully reveal answers to all these questions as more studies relevant to the average person are done.
In the meantime, here’s hoping the second senescence this month session produces more good results!