Glucosamine instead of Metformin and Rapamycin?

Zisos Katsiapis 

Here is a link to research that show decreased all-cause mortality among those who took Glucosamine. " A population-based prospective cohort study included 495 077 women and men (mean (SD) age, 56.6 (8.1) years) from the UK Biobank study."

"Conclusions Regular glucosamine supplementation was associated with lower mortality due to all causes, cancer, CVD, respiratory and digestive diseases."

"Regular glucosamine use is associated with a lower risk for total mortality (15%), CVD mortality (18%), cancer mortality (6%), respiratory mortality (27%) and digestive mortality (26%)."

https://ard.bmj.com/content/79/6/829

My first thought was that users of glucosamine usually have painful joints and that they also take NSAID - aspirin etc. And that could explain some of the disease prevention. But they say "the associations between glucosamine use and all-cause and cause-specific mortality were not significantly modified by sex, age, ethnicity, obesity, current alcohol status, physical activity, diabetes, statin and aspirin use"

Yes Glucosamine is interesting.But does not have a long history of use in clinical settings like metformin. But according to the study I refer to it is not a shot in the dark.  

My main question is: Am I already using substances that give me the benefits the Glucosmine will provide? In that case will there be a risk that glucosamine only will  add the possibility of negative interactions.  

Zisos Katsiapis with rapamycin you need to have comprehensive lab work done before you start and then ongoing every six months. This needs to be reviewed by doc. To me the biggest concern with rapamycin is that it suppresses mtor effectively neutralizing the benefits of strength training. You need your muscles as you get older. Hence knowing a bit more about when and how much to take are big questions here. So rapamycin today as I see it is only useful as adjunct treatment to calorie restriction.

With respect to our question on antioxidants dosing. First of all I don’t recommend taking any antioxidant supplements (excepting some vitamins if you have low blood levels) as they shorten your lifespan perhaps excepting besides some vitamins and glutathione, which seem to be safe. The antioxidant precursors like sulforaphane make more sense to supplement and are more promising. These I would take either in low doses everyday or intermittently 6 weeks on and 2 weeks off. Now if we are talking about antioxidant vitamins then I would recommend obtaining rda doses everyday.  For example you need vitamin c, which happens to be antioxidant, before your weight training to synthesize collagen afterwards. As you know other fat solvable vitamins like vitamin d don’t have to be taken everyday. 

Joe smith 

I'm curious about your statement that antioxidant supplements shorten your lifespan. I hadn't heard that. Would you expand on it, with some sources?

http://www.digitaljournal.com/article/129836

Joe smith 

you stated. “me the biggest concern with rapamycin is that it suppresses mtor effectively neutralizing the benefits of strength training. ”

I have been taking rapamycin for 6 weeks on a weekly basis and have found that my workouts are more beneficial than before I started. My increased gains in muscle mass and have strength are noticeable so I don’t think your statement can be true. The only thing that has changed otherwise is I seem to have more energy to do workouts and so have been able to increase my number of workouts. 

Stevan Lieberman Thanks so much for the n=1 post on Rapamycin and resistance exercise! I've been hesitant to add Rapamycin to my longevity intervention stack, due to concerns about exercise blunting. Metformin has been readily shown to blunt exercise.

I gained some comfort through some personal communications with THE Rapamycin guru himself, Blagosklonny.

He wrote "Amino acids do not make muscle stronger, exercise does. And Rapamycin potentiates strength"

https://www.mikhailblagosklonny.com/how-rapamycin-prevents-muscle-loss-and-sarcopenia-first-draft/

It has been shown that there are MTOR INDEPENDENT pathways to MUSCLE hypertrophy in humans.

So I decided to take the plunge, waiting for my first Rapamcyin order to arrive.

May I ask what triggered your taking Rapamycin, and what is your dosing regiment?

MAC Dr. Nir Barzilai is a MD who is a medical researcher and expert concerning metformin. From the podcast notes, here is a summary what he said during a podcast interview by Dr. Peter Attis, MD.

• He points out that while the metformin group had less muscle mass growth, the function was actually the same
• Nir’s main points:
  • In this elderly population, metformin kept the young profile of the muscle 
  • At the end, maybe you had less muscle, but you had the same function, and you gained by metformin protecting 500 transcripts that are aging transcripts

David H Not swayed. I am 55 yo, very lean and fit, following a strict ketogenic diet, OMAD (one meal a day) time restricted feeding. Glucose and insulin signalling are not any metabolic concerns; some days I am hypoglycemic. I am already doing some AMPK heavy lifting. I exercise daily 60-90 minutes, combined cardio (125 bpm/30 minutes) and whole body resistance training. 

Peter Attia has mentioned several times on various podcasts his concerns about metformin and exercise, and most especially for anyone who is very fit and far away from metabolic syndrome.

Metformin blunts muscle hypertrophy in response to progressive resistance exercise training in older adults: A randomized, double‐blind, placebo‐controlled, multicenter trial: The MASTERS trial

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826125/pdf/ACEL-18-e13039.pdf

" In men and women aged 65 and older, 14 weeks of PRT induced the expected increases in muscle mass and strength. However, metformin administered along with PRT inhibited these gains. DXA showed that metformin gained significantly less total lean mass and less thigh muscle mass than placebo. Likewise, CT analysis indicated that normal density thigh muscle area increased following PRT, but metformin blunted this gain."

Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351883/pdf/ACEL-18-e12880.pdf

"Our findings in older adults at risk for T2DM demonstrate that compared to placebo, metformin blunted the improvement in CRF by ~50% after 12 weeks of AET. Since CRF and insulin sensitivity are primary predictors of age‐related morbidity and mortality, these data raise concerns about broad recommendations for the use of metformin as a treatment to target aging"

Since CRF is the only proven longevity enhancement lifestyle intervention (DR and fasting have not been proven in human RCT, although in many other animal models) in humans, I wouldn't do ANYTHING that would blunt that intervention.

MAC My parents started talking about taking anti-oxidants when I was in my mid 30's and convinced me I should take them too.  Then the focus was on Vitamin C and the discussion mostly surrounded how ones body could not use vitamins as easily so one needed to supplement with higher amounts.  It got me reading and I started adding on different supplements.  I am now in my mid 50's an I have been able to tell that I didn't have the same energy or ability to heal for a while and ran across Dr. Green's website.  After reading it I googled sirolimus and this site came up.  I showed both sites to my primary care who then had a chat with Dr. Green and based on that both agreed to prescribe for me and has started taking the same dosage she has prescribed for me which is 4 mg once a week.

Stevan Lieberman  I’m glad that rapamycin is working for you. How much and how often are you taking? Also what brand and where are you getting it from? Also do you plan on doing before and after bloodwork? My personal experience is with the sirolimus 2 mg taken once a week obtained from Walmart. From my tests all I saw is that sirolimus succeeded in lowering my urine ph ;hence, putting me in the starvation mode. During 48 hrs after taking it, I could barely exercise.

Joe smith I am taking 4mg once a week.  It is prescribed so just getting it from cvs. I had a blood test before and then 3 months later. I have always worked out pretty regularly which I assume is why there was no difference between before and after. I will do another test in 6 months. All of my numbers are within norms. I felt like I had more energy the first couple of weeks taking it but since then not a significant difference. I am 55, not overweight and also take a number of supplements and have been doing so since my 30’s. 

Stevan Lieberman Also, I had no issues exercising after taking it, and in fact I found that I was able to work harder and since starting I am finding it easier to do more weight on weight lifting day  

Stevan Lieberman  I’m 6 foot tall and about 160 pounds, thin and muscular. I exercise 5 times a week. I can do a single leg sit to stand. I’m about 5 years older than you are.  I do take sirolimus with lithium, 500 mg berberine and 500 Metformin per day. As b and m are mtor suppressing together with lithium, they augment the effects of the sirolimus. This combined with my calorie restriction diet most likely suppress mtor to the point that I have to push myself to exercise within 48 hours of taking it. I also may be more sensitive to sirolimus than others. 
 

Joe smith You're strong.  I've never been able to do a single leg to stand and only workout with 150 lb bench (I workout 3 days a week).  I'm five foot 7 give or take and 165 pounds a little stocky. I take the lithium as well, 5mg. I don't really do calorie restrictions intentionally, I just don't get particularly hungry (my work has me sitting most of the day) so have a small breakfast of toast with a lot of olive oil and some nuts and blueberries and a lunch which is a full meal around noon and don't eat anything else for the rest of the day other than a spoonful of peanut butter around 5 sometimes (200 calories?). I am averaging between 1000 and 1500 calories unless I have a beer which is 2-3 times a week which I figure adds around another 150 calories.  My weight hasn't changed by more than a couple of lbs in years. I also find I am not particularly sensitive to any drugs / supplements.

I thought b & m did essentially the same thing, so why do you take both?  I also understand they both give you loose stool. Do you have an issue there? I do not understand why suppressing mtor makes it harder to exercise. Can you or anyone else explain?

Stevan Lieberman both berberine and Metformin are organic compounds but derived from different plants. Hence different mechanism of action. Berberine also lowers ldl-c and triglycerides, which you need when you take rapamycin. Berberine also counteracts negative side effects of Metformin.

Mtor is basically growth regulator. You activate it more growth, bigger muscles, etc., you deactivate it then you stop/slow down the growth. Recovery from the strength training involves activating mtor in presence of amino acids and includes muscle hyperthropy and conversion of the stem cells into muscle fibers.  Now if you suppress mtor then you slow down recovery from the strength training. So in my case when I take rapamycin it impacts my recovery as I train 5 times a week. So when I exercise next time within 48 hrs of taking rapamycin my mtor is suppressed, I’m not properly  recovered and I can barely go through my routine. 
 

Joe smith Ok, that makes sense, but you say strength training.  Does that apply to cardio as well?  Yes, I know that also includes substantial muscles, but everything is a muscle, re heart, lungs, etc.  Thoughts?

Joe smith Just doing a bit of a deep dive on berberine. You say you take 500mg berberine with Rapamycin? I've read some papers and references that berberine and macrolides (of which Rapamycin is one), are contraindicated?

https://liftmode.com/blog/berberine-side-effects/#_ftnref6

The enhancement of cardiac toxicity by concomitant administration of Berberine and macrolides

https://sci-hub.se/10.1016/j.ejps.2015.05.009

"Collectively, these results demonstrated that concomitant use of Berberine with macrolides may require close monitoring because of potential drug toxicities, especially cardiac toxicity"

As well, find many articles indicating concern over long term effects of Berberine, much less well studied vs Metformin.

https://diabetesupdate.blogspot.com/2013/08/berberine-works-but-may-very-well-be.html

I assume you are under care of MD, since metformin and Rapa are typically needing prescription?

Do you take anything to help with bioavailability of berberine?

Since I am strict keto/OMAD, my glucose and insulin are typically very low, so I wasn't thinking I'd need berberine to help dampen down any potential elevated glucose that might present itself when I start taking Rapamycin. 

Joe smith very strange. I take 10 mg a week and am an avid hiker and mountain biker. Ramamycin has no effect at all on my workouts

MAC well yes rapamycin  is micro-glide but the paper focused on antibiotics and it doesn’t appear to mention rapamycin. I think it would be a stretch to think that it covers it too. Berberine actually appears to be heart protective.  and yes berberine is not as widely studied as Metformin; hence, I only take 500 mg and only do it once a day. Berberine half life is about 3 hrs so I don’t overload my system with constant berberine drug pressure. I also cycle it on and off. To increase absorption I take berberine and rapamycin with fish oil.

Paul Beauchemin well according to the research I reviewed it should impact resistance training in mice by 50 %. Anyway I wish Dr Green publish some studies to give us more insights here.

Paul Beauchemin Must be placebo. Clearly from the literature that I recently attached to posts on this topic, mTOR inhibition is a no-no  in terms of repairing muscle fibers after exercise. Use  will also contribute to sarcopenia and frailty in seniors.

In terms of Joe Smith's comment, fish oil stimulates mTOR in terms of muscle repair. It also inhibits mTOR in terms of preventing neurological diseases. Biology is complex. 

Peter H. Howe a brilliant personal attack!

Joe smith https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4594297/

Peter H. Howe This is a really interesting debate. As it relates to aging and sarcopenia, it's now contested that it's actually OVER-ACTIVE mTOR which contributes to sarcopenia, and Rapamycin can reduce mTOR and geroconversion/senescence and actually REDUCE sarcopenia.

I've already posted before on communication from Blagosklonny:

“Amino acids do not make muscle stronger, exercise does. And rapamycin potentiates strength” The link explains the theory.

https://www.mikhailblagosklonny.com/how-rapamycin-prevents-muscle-loss-and-sarcopenia-first-draft/

A recent review paper from Cambridge University UK.

Dietary protein, exercise, ageing and physical inactivity: interactive influences on skeletal muscle proteostasis

https://sci-hub.se/https://doi.org/10.1017/S0029665120007879

I wrote to the author asking about the mTOR over-activation causing senescence and sarcopenia theory, and Rapamycin possibly ameliorating. He replied. "I have an on-going project grant also testing this hypothesis."

I am intrigued on my n=1 response when I start taking Rapa. I am currently 55 yo male, in super cardio and skeletal muscular shape, daily exerciser, who also takes testosterone. What will rapa do to my daily bouts of exercise and cardio and muscular response with once weekly rapa?? The half life is 3-4 days in blood, but what is CELLULAR level?

Paul Beauchemin I will review the article, I know it mentions 42 female mice of particular strain. At best this is enough to form a preliminary null hypothesis.  I’m also familiar with newer research published in the same magazine, which draws different conclusions. Again until we have human data and larger sample size with longer duration, we just don’t know. 

Joe smith The fact that Rapamcyin, being a macrolide, is not specifically mentioned in the article hardly gives me scientific comfort. Surely they would not have listed every macrolide in existence, but common ones. But I think your heeding the safety of long term Berberine supplementation by limiting intake to 500mg/day is prudent measure of concern.

Is the metformin and Rapamycin doctor scripted, or are you flying solo? And the berberine, although not needing a script, your own intervention or doctor approved?

MAC Metformin and rapamycin is doctor prescribed. Berberine is really on my own that said  I fully disclose to my doc what I’m doing and hasn’t heard any objections or concerns yet. I guess being conservative with the berberine helps. My doc wanted exhaustive blood and other tests before I started on rapamycin. As I mentioned, rapamycin has decreased my urine ph from an optimal range of about 6.2 down to 4.5. After I stopped taking rapamycin,  it went backup to 6.2. hence word of caution you can get kidney stones at such low urine ph. I think that the explanation for the low ph is that  rapamycin really induces  “starvation” like state.

Joe smith Thanks for sharing. I'm on strict keto, one meal day diet, and haven't had any issues, although to be honest, don't recall my doc asking for urine PH to be tested. My keto is plant fat based, not animal, and I don't overload oxalates (major cause of stones) and stay hydrated. My protein intake is max 20% macros of total calories, rest in plant fats. Been 4 yrs, no health issues so far. Duly Noted.

So you're back on Rapamycin, and doing anything to address the urnine pH issue?

Any significant change in your biomarkers baseline after Rapamycin?  

MAC no real change in my bio markers. A1c always around 5.2, hdl about 80, triglycerides 100 and ldl about 130. To address urine ph I take potassium citrate now foods supplement and eat lemons. 

Paul Beauchemin Response in kind.

Joe smith The after lipids is with berberine and metformin correct, which would help blunt glucose and possibly lipids? Do you have results before/after with just Rapamycin? Sounds like you are hacking what comes your way! 

MAC without Metformin and berberine my a1c is 5.3 with Metformin and berberine after 6 months and longer, it is 5.1 - 5.2, Ldl without berberine is about 180 and after six month on berberine it is 122. Berberine doesn’t seem to affect my hdl and triglycerides much before and after hdl 80 and triglycerides about 100.  When I take statins 20 mg Lipitor no berberine after 6 months my triglycerides go down to 70 and my ldl to about 65. Hdl stays at about 80.

MAC The following is from an 80 yo who is trying to make it to a healthy 100 which has less than a 1 % probability.  It gives me something to do and science is ever changing along with the multiple type 1 and type 2 errors in any scientific undertaking that has a very wide 95 % confidence interval. What can help me may be detrimental for someone else. With that said:

In my opinion rapamycin is dangerous for a senior.  Not considered so far is the potential adverse impact on a seniors immune system.  You can ask Mr. Google and find that rapamycin inhibits the innate immune system. I am taking many steps to insure my immune system is properly stimulated and functioning, The last thing I need is interference.

I saw your earlier reference to the Blagosklonny draft manuscript.  I prefer to take a different path and it appears to be working for me. I am going to continue my 1 gm/kg protein/day with ~ 40 grams of that from whey protein which also stimulates my immune system. It also contains all the essential amino acids in the proper amounts. It is ( along with egg whites) natures best protein. As you probably found there a multiple peer reviewed papers on the need for seniors to get more protein in order to prevent sarcopenia, some suggest up to 2 gm/kg/day. . 

Before attaching several papers on the issue, you should know that I  also consume ~ 5.5 grams/day of EPA/DHA (fish oil). I have been taking this for 25 years after I had an emergency bypass. It is a "miracle" drug that is critical in terms of me reaching the 100 mark. More on this latter. 

The following papers should explain my rational as to why I am going to stimulate mTOR in the interest of preventing sarcopenia and why I referenced my consumption of fish oil.

https://pubmed.ncbi.nlm.nih.gov/19188252/

The second reference is to a "sales pitch" article but it contains references to fish oil ,and the  stimulation of mTOR in the interest of preventing sarcpenia.

https://www.intelligentlabs.org/how-omega-3-supplementation-increases-muscle-mass-and-strength/

Another on fish oil and sarcopenia that references mTOR.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4936484/

You should be aware that maintaining your testosterone,  estrogen and DHEA are also critical in preventing sarcopenia and also prevent osteoporosis, dementia and a host of other ailments. They blend in with fish oil,  proper diet and exercise along with the ability to change your mind.

I note that your previous post on metformin failed to mention that it inhibits testosterone production by inhibiting leutenizing hormone.  I stopped its use about five years ago due to this problem. I also stopped a severe 5:2 diet with rigid 18:6 eating interval in May of this year after 2.5 years. It also severely limited my testosterone production.  You can verify that calorie restriction and metformin  impairs testosterone production with a simple google search. 

MAC You are apparently where I was 25 years ago after my emergency bypass. After an extensive search, I got lucky and found a cardiologist who integrated a statin with fish oil to prevent a future heart attack. I can assure that over the years, I have encountered a number of cardiologists who claim that fish oil is worthless.

In this regard and in the interest of preventing dementia in your case, you might want to examine the attached review of fish oil benefits in preventing various forms of dementia by inhibiting mTOR ( 13 co-authors, 50 + pages ~250 references).  Its introduction contains  a extensive review of fish oil benefits. There are approximately  7,000 similar references on fish oil benefits. . 

https://idus.us.es/bitstream/handle/11441/96286/mTOROmega3.pdf?sequence=1&isAllowed=y

Keep on truckin, keep your triglyceride/HDL ratio at~1 and have a good new year. If those Brits publish that  paper, please let me know.   

Peter H. Howe Healthy 80 yr old..you are way ahead of the game Peter! Less than 1% chance...depends, are you APOE 2/3, they are highly enriched for longevity vs. say APOE 4/4. I am APOE 3/4, so I have my work cut out...must work that much harder.

 ApoE e2 and aging-related outcomes in 379,000 UK Biobank participants

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343499/pdf/aging-12-103405.pdf

Varying Effects of APOE Alleles on Extreme Longevity in European Ethnicities

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330482/pdf/glz179.pdf

APOE2 is associated with longevity independent of Alzheimer’s disease

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588231/pdf/elife-62199.pdf

Re Rapamycin and innate immunity...you missed that clinically, weekly intermittent dose ONLY impacts TOR1, and leaves TOR2 (innate immunity) unaffected. You are referencing chronic DAILY high dosing in transplant type scenarios. Many people taking intermittent Rapamycin are having their immune system checked, and in control. You can google this.

I have been taking 3g/day DHA, and I eat wild sockeye 3x/week plus sardines. My last RBC Omega 3 blood test was 13%, very high. When I prick my finger for blood ketone measurement, the blood squirts out. I am aligned with you, I think DHA is super beneficial. DHA, keeping TG/HDL low, and very high cardio respiratory fitness are major interventions to prevent CVD.

My philosophy at 55 yo is to PREVENT...and not wait for a chronic disease to manifest. Preventing a major mortality event is going to greatly increase my healthspan and mortality odds.

I leave you with this 80yr old (at the time of the video) to consider what is truly the key metabolic lifestyle intervention to successful aging.

https://www.youtube.com/watch?v=1IDbO8v0YOk

His muscular physique didn't come from DHA or protein or pharmacology. It came from EXERCISE...that is THE key to skeletal muscle. That's what stimulates anabolic growth and is THE key to preventing sarcopenia. How many seniors are pounding the weights like he is? I've never seen a senior in the gym doing this type workout. I hope to continue this type resistance training as long as I can.

Sarcopenia (barring some chronic disease that prevents exercise) in seniors is preventable. Seniors are not inactive because their bodies are falling apart, their bodies are falling apart because they are inactive.

MAC Have differences of opinion on several issues--it is biology.

I am well aware of the APOE issue and  I am APOE3 homozygous. Women in my family have tendency for alzheimers. Men, if they make it past cardiac arrest, it is ministrokes followed by the big one. We have very little incidence of cancer, probably due to low levels of IGF-1.

It is my opinion that the most important thing one can do in preventing mental illnesses related to the APOE gene is to follow the Bredesen protocol.  

http://www.aging-us.com/article/NjJf3fWGKw4e99CyC/text

As documented in this  paper he reversed AZ in 9 of 10 patients and 6 of those returned to work. He has authored a book on the subject which goes into more detail. As I understand it, some enlightened neurologists are following it in terms of treating dementia. 

There are 3 steps which in general are:

1. No simple sugars, no eating between 6 pm and 6 am to give microglia time to clean up and some calorie restriction

2.Return  hormones to youthful levels,  supplement with  fish oil and critical vitamins (D and B ) if they are low, and some additional supplements such as ashwagandha

3. Remove toxins such as lead, mercury and pesticides.

It is my opinion that the protocol is also an essential part of of an extended health span as it treats more than dementia. .

Thank you for clarifying my issue with rapamycin and suppressing the immune system. I will however refrain from from it until I see a good risk assessment from some group like Forever Healthy. There are just too many unknowns. 

I recognize the need for senescent cell removal, and have initiated use of fisetin based on comments of a number of persons on this form, risk assessment by Forever Healthy and  studies and current trials at Mayo.  It is also a mTOR1 inhibitor . I follow the Mayo protocol, with some exceptions, and the intermittent use may suffice in terms of mTOR.  Wish I had convenient way to measure effect levels as I have with blood test for statin and fish oil and cardio protection.

In terms of fish oil my Omega Index is 9.16 %. Would like to get it somewhat higher, but if increase fish oil, I will start getting contusions. Had to stop baby aspirin due to the interaction of the two  and almost daily bruises. Getting old. Cardiologist told me to stop the fish oil, not the aspirin, due to my history. Told him thank you but no thank you.

Strongly suggest you incorporate EPA in your fish oil. It is the primary component that suppresses inflammation. Check your IL-6 and tumor necrosis factor alpha. It does not affect CRP according to the literature.  

That guy in the video looks old. Check out his face. Too much stress from all that weight lifting. Charles Atlas only lived to 82 as I recall. The average life expectancy of a male in the vegetarian Seven Day Activist community in La Jolla Ca. is 95.

There is no question that exercise isn't important, but it cannot get you to 100 on its own.  Most seniors simply do not have the ambition to do what you are doing, due in most part to a host of deficiencies. 

Thanks for the post. It keeps me alive along  with the 110 deep knee bends with 2, 20 lb weights that I have to do next.

Peter H. Howe apoe3/3 well that’s a better starting point, but still 60% of AD is 3/3. But apoe is NOT singularly causative, it’s a complex polygenic risk disease. My mom had AD, and maternal AD increases APOE4 risk. Sigh. So for me, my journey is neurological avoidance based. CVD or cancer death is not a known early mortality pathway in my family tree. 

Been on the Bredesen protocol for 4 yrs, started immediately after taking on a Functional Medicine Doctor. We push it to even farther ranges like overlaying keto/OMAD, DHEA/hormones, Vitamin D, toxins, iron dumping, much higher exercise (the protocol is lacking in exercise) 

Sedentary lifestyle and insulin resistance is the bane of western disease. Too many excuses and people waiting for “sick care” medicine to help them live longer AFTER you become chronically ill. 

But it did take discovering I was apoe 3/4 4 yrs ago to give me that “scare” self motivation to PREVENT disease while I still have window. 
 

Exercise is my #1 lifestyle intervention for longevity. Will keep running and lifting weights as long as I can! 
 

Will keep you posted on my n=1 Rapamycin experiment. I haven’t even told my doc yet I plan on adding this hack! I did ask him to explore it with me earlier this year, and he was open to it. 

Joe smith https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3765582/

MAC See attached. Contains brief section on rapa and call by AgeXX for volunteers.

https://www.longevity.technology/a-year-in-longevity-progress-perspectives/?utm_source=ZohoCampaigns&utm_campaign=Longevity.Technology+News&utm_medium=email.

Joe smith Started my first dose 4 mg weekly Rapamycin. No obvious effects. Most importantly, my exercise regiment and recovery seem unperturbed.