#21

Pioglitazone (another TZD) is one of my all time favorite longevity compounds. It’s readily available and I shared about it quite a bit in the Facebook Rapamycin group. E.g. Pioglitazone

Cocoa is turning out to be a no brainer supplement for longevity. Because it has numerous human trials showing benefits now! Plus ITP life extension. Further reading Cocoa

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#22

Very nice writeup on pioglitazone, though notably lacking in one of the biggest concerns: increased incidence of bladder cancer, which is strongly correlated both dose and time dependent. I too have explored pioglitazone (Work In Progress) in this thread:

I also think it’s pretty important to look at combining use of pioglitazone and other drugs. Statins, which you mention, but also telmisartan which has several possible synergies while possibly alleviating some of the undesirable side effects, such as weight gain. Also, SGLT2i, such as empagliflozin which might reduce edema and perhaps lower the HF danger.

As always, healthy aging and life prolongation is complex and unlikely for any single drug to have optimal effectiveness alone. Instead, carefully calibrated polypharmacy is called for, adjusted depending on one’s particular phenotype.

Atm, I’m doing lipid lowering therapy (pitavastatin, bempedoic acid, ezetimibe), glucose control (empagliflozin), BP control (telmisartan), and soon low dose (7.5mg/day) pioglitazone. Epicatechin I’m hoping to cover through dietary sources, daily cacao and green tea. And of course, rapamycin - 6mg/1-week. To the degree that I could, I’ve explored the possible interactions of these various molecules, but naturally, it’s a continuing and never ceasing work in progress (WIP).

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#23

Great! Any reason you’re doing pitvastatin over other statins?

I’m currently on rosuvastatin + bempedoic acid & ezetimibe.
But always keeping an eye out for the safest in class among the statins.

#24

As bladder cancer (BC) is very rare, a modest increase in BC risk is probably not very significant.

The best cardiometabolic drug for NASH, today, is retatrutide (stage 3 clinical trials about to be finished). I’ve been on it for 2 yrs or so. It’s amazing – next gen tirzepatide. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial | Nature Medicine

I’ve been on Rosuvastatin (2.5mg), Lisinopril 10mg, Aspirin 80mg. Added ezetimibe on and off (still trying to get used to it). Pio 7.5mg is great but I think I’m getting too much bone marrow supression these days (so I’m not on it).

Nice group on heart disease risk: Redirecting...

Supplements:

  1. Daily green tea + hibiscus tea (1 mug)
  2. Daily coffee (1 mug)
  3. Vitamin D3 (2k-4k IU/day)
  4. Fish oil (1.2g-4g/day)
  5. Alpha ketoglutarate (AKG) 250mg/day
  6. Beta alanine 400mg/day
  7. Alpha lipoic acid 300mg/day
  8. Cucumber + Celery juice (1/2-1 cup)
  9. Aged Garlic Extract
  10. Magnesium, Calcium, Chromium, Fiber

Plus mediterrenean keto diet recently.

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#25

I’m glad to see epicatechin had a life-extending effect after all, however small. Maybe there’s a similar compound with even more potent effects.

I’m looking forward to hearing how GlyNAC turns out. Neuro-NAC might be an even more powerful supplement to try for life-extending purposes.

I also will test out black ginger to see its effects. (A personal n=1 test).

#26

I wonder about EGCG, also. It has been claimed to inhibit DYRK1A, one of the genes of the DREAM Network (so does EGCG result in an increase in DNA repair?), though I’m not sure the same is true of plain epicatechin.

#27

Interesting

  1. it improves mitochondrial dysfunction, potentially even more than aerobic training
  2. redistributes fat from muscles and beta cells to subcutaneous fat
  3. is the only drug that increases insulin sensitivity
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#28

The results from the ITP (Intervention Testing Program) can absolutely be seen as a strong signal that excessive insulin signaling (hyperinsulinemia) is a key accelerator of mammalian aging. This aligns very well with Dr. Ben Bikman’s reasoning and the broader scientific understanding of the insulin/IGF-1 signaling pathway in aging. Insulin levels can be seen as the canary in the coal mine.

ITP, some of us here and biogerontologists know that the Insulin/Insulin-like Growth Factor 1 Signaling pathway is one of the most evolutionarily conserved pathways regulating aging. Reduced signaling in this pathway is strongly associated with increased lifespan and healthspan in species from worms and flies to mice. And some say that, low insulin signals is strongly associated with increased lifespan and healthspan even in long lived humans.

Excessive signaling is associated with accelerated aging and age-related diseases.Insulin is Not the Enemy, Hyper-insulinemia Is. Insulin is an essential anabolic hormone. We need it to live. The problem is the chronic, excessive levels. The ITP provides strong correlative signal for this reasoning.

But these drugs (drugs for type 2 diabetes) have other proposed anti-aging effects, like effects on mitochondria, AMPK activation, that may be independent of insulin. Lower insulin likely contributes to these other beneficial effects. High insulin activates besides IGF also mTOR.

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