Some of the longevity drugs that work in mice probably help humans delay cancer.
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Right. These however are not mutually exclusive. Even if longevity drugs donât prevent modern lifestyle death and disease causes, they still work. Btw., true longevity drugs are supposed to work by slowing ageing, which delays these diseases, and there seems to be evidence that at least in animal models rapamycin does so. To me, rather than dropping longevity drugs, this is a reason to escalate the use of drugs that prevent or ameliorate these diseases, like statins and the like.
Rapamycin - or longevity drugs - are like a healthy diet, we know that a healthy diet leads to a longer life. But what if you live in an unsafe neighborhood, and there are regular shootings? Would you say âgee, Iâm not going to bother with a healthy diet, because a healthy diet does not prevent my being shotâ. The solution is to keep the diet and move your place of residence. Same here, just because rapamycin does not prevent modern lifestyle diseases (and Iâd dispute that, at least in animals), doesnât mean it makes sense to drop it. Dropping rapamycin will do nothing to cure heart disease, cancer or T2DM.
However, there is a much more interesting argument, brought up by Matt Kaeberlein. What if rapamycin both slowed down aging and killed you prematurely? That might very likely be the case. Now you truly have a dilemma⌠except the solution is very simple.
How can rapamycin delay aging and yet kill you way ahead of your natural time? Because while rapamycin slows down your aging, it also, especially at higher doses, might depress your immune system and you might die of an opportunistic infection. In lab animals you donât see that, because labs take pains to shield animals from pathogens. So whatâs the solution? Drop rapamycin? No, the solution is the same as with the diseases above. Retain rapamycin (although you might want to mitigate the danger with dosage), but get all the vaccinations you can for pathogens you might be exposed to, and minimize unnecessary exposure to such pathogens in the first place. Win-win.
Same with the diseases you mentioned. To me thatâs a compelling argument for carefully curated polypharmacy. I take rapamycin, but I also take a bunch of drugs to ameliorate the chances of my getting these diseases: lipid lowering therapies (statin, bempedoic acid, ezetimibe etc.), blood sugar control (SGLT2i, soon pioglitazone, perhaps acarbose), blood pressure control (telmisartan down the line). Exercise and a good diet are a given - Iâd do that regardless. Itâs not an either or. I want maximum impact on healthspan and if lucky maybe even lifespan, and the first step is diet, exercise, stress and lifestyle adjustments. But that only takes me so far. The next tranch is taking medications proven to enhance healthspan or lower health risks: lipid control, blood glucose control, BP control and vaccintions. And then I roll the dice with a cherry on top: longevity drugs - thus far rapamycin, but weâll see what science brings us in the future. Iâm not dropping the longevity drugs just because other risks exist, I lower the other risks instead. Furthermore, we have evidence from the ITP that many of these work synergistically: rapamycin works even better with for example an SGLT2i, acarbose, metformin etc.
These lifestyle drugs (statin etc.), get me into the door of the casino. Rapamycin gets me some chips I can place on the roulette table. I for one am not going to reject the rapamycin gambling chips. I am gambling that Iâll come out ahead instead of going bankrupt, but thatâs the nature of the game. YMMV.
EDIT: incidentally Matt Kaeberlein published a short on yt. contrasting short term vs long term effects of rapamycin in mice. Short term, there were metabolic derangements of glucose control, but longer term there was an improvement in these parameters compared to the baseline. A nice illustration of why it is important to focus on long term outcomes and not short term mechanistic perturbations in evaluating these drugs:
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I go off and on but this is gonna make me resume taking estradiol
CCTA came back about as expected â stenosis under 70%. Not great, but not immediately critical. Triple lipid therapy might be the ticket.
Iâve got an appointment with an InstaLab cardiologist (Dr. S. Winiarski). He looks solid â apparently into longevity, so I can come clean and get his take on the whole medicine chest.
After the triple whammy â AK, CAC, and a pulmonary nodule â I paused E3 for a bit. Starting it back up this weekend. The noduleâs still lingering, so Iâm holding off on rapa for now (not keen on immunosuppression until thatâs resolved).
E3 isnât noted for oncogenesis â didnât hurt the ITP mice, even though theyâre cancer-prone. But cautionâs warranted. Weâre still in early days here. Heck, E3âs umbilical cord hasnât even been cut yet (pun very much intended; raw placenta anyone?
).
Iâm liking the looks of InstaLabs â might spring for their monthly concierge plan.
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Quick follow-up to my placenta quip (yeah, that one).
Turns out itâs not just a weird hormone joke â itâs a real thing. Hospitals often sell placentas to biotech and cosmetics companies. Theyâre rich in stem cells, collagen, and growth factors, so thereâs real demand.
Whatâs messed up is that this often happens without the motherâs full understanding â just a vague âmedical wasteâ form slipped in during a chaotic, vulnerable moment. No clear disclosure. No compensation. Just standard operating procedure.
So yeah â this isnât just quirky biology trivia. Itâs capitalism extracting value from mothers and newborns, at one of lifeâs most sacred and exposed moments.
Joke withdrawn. Eyes open. E3Male:HumanNof1 still learning, E3Male:HumanNof1 apologizies
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Estriol update + ITP paper correction
A quick note on the (yes, seminalâfirst-of-its-kind) ITP paper: GeroScience issued a correctionâwhat the paper first called â16-hydroxyestriolâ in multiple spots is correctly â16-hydroxyestradiolâ (i.e., estriol, E3). The journal lists five fixes (title, abstract, intro, discussion, Table 1). SpringerLinkScholars @ UT Health San Antonio And I canât be too harsh on them as in this thread I found several places where I used the term E2 instead of E3, which I have corrected. So it happens to the best of us:)
Iâd paused most supplements to get my lipids in line (ugly CAC score), but Iâm restarting with a test run of topical E3. About three days in, I noticed the usual appetite effectâlittle interest in dessert/candy/cookies after dinner. N=1, subjective, but thatâs my repeat experience.
Sharing personal experience, not medical advice. Also, Iâd skip E3 in younger menâpossible testosterone/fertility impactsâso if youâre still building a family, this is a hard no-go. imho
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This is a link to the original ITP paper with the mis-information/labeling/naming. which annoyed me no end.
Lifespan effects in male UMâHET3 mice treated with sodium thiosulfate, 16âhydroxyestriol, and lateâstart canagliflozin
Obviously Iâve embraced E3 and Iâve bumped up dapagliflozin to be on the essential medicines list for me. I took a hard pass on thiosulfate, the required dosing level didnât seem feasibleâŚ
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Coming up on the one-year mark as E3-N1-Male, so time for a recap. Iâve attached my latest labs and screenshots of the markers I watch most closely, and at the end I have my full lab results.
My E3 use has been a bit uneven. After the high CAC scare I hit pause for about 10 weeks to get my lipids in order. Since then Iâve restarted: 3 mg Fri/Sat/Sun every other weekend, alternating with rapamycin weekends. Iâve also picked up some E3 cream that I use here and there when the mood strikes. All told, between the pill cycles and the cream a few times a week, I figure Iâm getting roughly 30 mg of estriol systemically each month.
In the full panel there are a couple of odd readings, though unrelated to E3. Iâve had what looks like mild anemia for years â those low blood markers showed up well before I ever started E3. My PCP hasnât been concerned, and Iâve had no symptoms. I even tried iron and B-vitamin supplements, but the numbers never really changed, so Iâve come to accept them as my ânormal.â The labs also show elevated urine glucose, which is expected since I take dapagliflozin.
The main red flag is that my Levine score has taken a noticeable turn for the worse. Earlier I was showing more than a decade younger; now it reads a pheno age of 65 against my chrono age of 72. I donât know why, but itâs clearly a âworseningâ of a recognized metric, and that canât be good. That said, I donât see any obvious way the Levine markers would tie directly to E3âs known effects.
So I plan on continuing my current regime. If the Levine pheno age keeps worsening, Iâll change course. Until then its straight sailing for me.
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Estradiol has trended up as might be expected.
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My basic T is up from the baseline pre-dosing 200ng level. I have no âsymptomsâ to complain about. My libido is fine. I do PDE5âs, tadalafil every other day and sildenafil occasionally, and those greatly help expand blood flow. So yes, the T numbers donât look too beefy, but Iâm feeling fit and firm, so these relatively low numbers donât bring me down.
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And these free testosterone levels donât bother me either. Some might scoff at the 67 bioavavalilbe testosterone, but I actually feel pretty good about it. Itâs 4x above the lower RR limit.
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FSH and LH werenât taken at baseline. I took my first blood test of these AFTER starting E3. And the FSH has been over RR the whole time. While the LH has been well within. I donât know why. I think someone mentioned that it is an âadaptationâ to keep sperm production up.
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Very interesting results. Thanks for posting!
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Tom_Clark, the blood work looks pretty good to me and definitely better than mine. By the way, are you hypothyroid?