CR is great except for the constant cold and hunger and outright daily misery that makes you wish you were dead every single moment. 
I’ll take Rapamycin instead for the same benefits and fewer side effects.
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Thanks for the kidney references. I am not fully convinced but at least it is a plausible explanation.
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Definitely Cypionate, testosterone - TRT starting at 50 years. I started at 62 years. Matt Kaeberlein states was the best thing he did … after waiting, next to Vitamin R… rapamycin. He is 54 years in 2 days.
Doxycycline weekly… 100 mg.
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I wish sites like this had a commonly editable spread sheet where top NN lists can be in a single place then smeared over 100+ posts. Anyway.
I’m shocked, just amazed that HRT, all hormones replacement therapy was not in any (or I missed) top 5 lists. Both sexes; estrogen (for men, it aromateses from TRT), testosterone, progesterone (no need for men), pregnenelone (LEF loves pitching this) my health coach tips 5mg (not 50) micronized, DHEA and importantly thyroid I take NP thyroid.
=== now hitting
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DIY self injected exosome sources. Got my 25B exosome delivery on dry ice yesterday. We will split it Sat. $1800 from a private org channeling a top name source. Money no object, said to be best if quarterly… A member of this group just injected 75B dose post shoulder reconstruction surgery.
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Once hot but now questionable; A product called Cell Factor (googleable). The beneficial insides of exosomes but without the variablity of an exosomee source. TBD
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plant based exosomes. Several companies have product for topical/skin use. TBD if ever become injectable.
=== Not yet settled protocols pre any TRIM - esk type trials, bearly concensus in private health groups;
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klotho; my experience with Klotho-a and now klotho-1 is nothing noticable. BUT same with rapa and nearly the same for HRT. Maybe holding flat is a gain in and of itself. :>
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VD-11; a general systemic up regulator. My order hasn’t arriived and just the coaches reviews of major up regulation, feeling better. TBD
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Fox-03 yet another compound in the KLOTHO chain in/near the mitochondria
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met enkephlin (??) an endogenous canabinoid good for pain
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URB-597 blocks the breaking down of endogenous canabinoids. Another help for pain, anti-anxity BUT feeling better in general. TBD.
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I’m close to but not in the direct flow of case studies from professional athletes/Olympic folks. In the money no object level; amazing recoveries and performance improvements. Eventually someone close to these folks will leak out the whats.
I suspect theres alot more compounds on the near horizon that are NOT out of patient targeting drug co labs, but out of small labs by genuine benefits driven private chemists.
True #1 line item on this list is sleep, next or close with clean water, clean and nutricious for you (individualized) food. An appropriate typee of exceresize.
But not far down the list are some new compounds more effective then rapa. We just need to get compound names, sources, and more DIY experiements like we have been doing here.
Good luck, curt
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I think this pretty much covers it. I don’t think there is any need for more. Maybe could add Selegiline since that has shown potential.
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I don’t understand the doxycycline love-in. Doesn’t it disrupt the gut biome like other antibiotics?
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Strong second for gut health, sleep and minimizing immune load.
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Yes, I would be cautious with it: One course of antibiotics can change your gut microbiome for years (New Scientist)
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Is this true for subantimicrobial amounts of doxy? e.g. 20mg BID?
Mikhail Blagosklonny said it was a good weekly idea… I have been been using at least 4 years.
Keeps all the parasites out of your system.
Maybe my nightly kefir at bedtime helps.
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I read your sleep newsletter. It’s very good.
Has anyone here tried pioglitazone instead of metformin for metabolic/longevity purposes? Metformin mostly lowers liver sugar output, while pioglitazone works more slowly but seems to improve fat cell function and mitochondrial health. Curious what real-world experiences or trade-offs people have seen.
That is a good question. My stack is shorter than yours… for me, I’d like to try microdosing GLP1 at some point when it’s easy.
This year I’ve got a number of things I’m interested in… SS-31, as I suspect that could have positive long term benefits. I’m also interested in Orexin for targeting Spontaneous Physical Activity (SPA) and Non-Exercise Activity Thermogenesis (NEAT). In both cases finding high quality suppliers at reasonable cost is the issue, so I have yet to jump on yet.
I can see some value in pulse dosing Maraviroc (a few months on, a few months off?) for muscle and brain benefits.
I’m also refining my fiber/fermented foods approaches (for butyrate production, etc.), trying to figure out how best to work them into my dietary habits, and what a good mix is that works for me.
My primary action area is refining my workout schedule; increasing strength and VO2Max, making things more efficient. I’ve got Blood Flow Restriction (BFR) cuffs and will start using those soon.
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Maybe why it is not so popular:
Effectiveness: It may take 2 weeks to see a decrease in blood sugar and up to 2–3 months for the full therapeutic effect to be felt.
Pioglitazone carries several serious warnings that require medical supervision:
- Heart Failure: It may cause or worsen congestive heart failure due to fluid retention. It is contraindicated in patients with established NYHA Class III or IV heart failure.
- Bladder Cancer: There is a possible link to an increased risk of bladder cancer with long-term use.
- Bone Fractures: Increased risk of fractures, particularly in the hands, upper arms, or feet of women.
- Liver Health: Though rare, it has been linked to acute liver injury; liver function tests are often required before starting therapy.
ref
Common Side Effects
Common Side Effects
- Edema (swelling in the hands, arms, or legs).
- Weight gain.
- Headache, muscle pain, and sore throat.
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Another drug in this drug class did well in the ITP although mice don’t really die of heart issues
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Have you tried modafinil or armodafinil before? If no, I’d consider trying those first.
So you have something to compare to if you ever do get access to the newer orexin drugs.
One of your posts on the thread you linked above (post #2 in the thread) mentions modafinil “Acts partially through the Orexin system”.
Along with some other good ideas such as bright light “Bright light (>10,000 lux) upon waking is required to synchronize the Orexin pulse”.
Caffeine “upregulates Orexin receptor expression”.
Doing those 3 together (modafinil, caffeine, while under bright light for some time) would be a powerful combo.
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I took it for 1 year or so. The problem is that it makes the fat cells more insulin sensitive and I got from 14% DEXA body fat to 16%. I’ve switched to Imeglimin a few weeks ago. Too early to know if that works though. I will report back later.
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I’d be tempted to still add a low dose BP drug. I hear they may provide other benefits on top of lowering BP.
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Actually, that’s horrible advice. I did that and my BP went so low I passed out in the bathroom and hit my head. That could have killed me. Never take BP meds when you have optimal BP as too low of a BP is a very bad thing. Of course my SBP was dipping into the 80s and 90s at that point.
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I guess it depends on person and the dose and which medication you take. I had bought (about year ago) some captopril 25mg and I started taking it about a week ago. It hasn’t made much of a dent. my BP is usually good 115-125/70-80 and now is more consistently 110-115/70-75. But I was thinking of taking telmisartan instead. BTW, I know someone that has been taking BP lowering drugs for last 45 years and he is a very healthy looking 87 and last time i spoke to him he thinks the reason he’s still alive it is because of the BP lowering med.
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