#64

Just out of curiosity did you ever try time release Metformin. My wife ( a doctor) tells me that most diabetes patients in the UK end up switching to time release to avoid the (mainly gastric) side effects

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#65

No… to be honest, I am very pleased with Acarbose. My gut feels great 4 plus weeks on it.

Also, its clinical track record in combination with rapamycin for longevity is better than Metformin.

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#66

Hi Agetron and other “age” test takers. No science URLs being shared, just asking a question(s):

  • My looking at the age tests what they measure, I ask; can OTHER life style practices negate or push the underlying test measures to be better or worse?
  • If one becomes overly confident that rapa negates bad life style choices and over indulges can one blame rapa for not reducing age tests?
    I’m not suggesting anything, just that us citizen scientists need to be rigorous in our self experiements. Keep good diaries on what we eat, drink, nutricals, bad vs good foods, etc along with our rapa dosing.

What if I took rapa for a year, but I found I really really had a love of good Scotch and upped my consumption? Just a nutty example of why high rapa may not be the root cause showing ever dropping age on these (possibly simplistic) age tests.

Best to all, curt

1 Like
#67

Repeating what I heard on a youtube by a researcher on a list of the anti-aging compounds; acarbose produces more gas on a wheat diet vs low carb vs rice. One might have varying experiences on acarbose depending on what else is in your diet.
Best to all, curt

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#68

Thanks Curt…

Definitely it is a balancing act of supplements, diet and lifestyle.

That said the only crazy change in my life was upping my dose to about 36 ng/mL for 7 months. With weekly dosages. No recovery time.

Discussed with the GlycanAge Ph.D. researchers they thought that I was over dosing… too.

Now 1/3 the dose 12 ng/mL and longer recovery 10 days. Will see if that moves the needle back.

If not… rethink it all.

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#69

Jason, many thanks for sharing your Rapamycin observations, the more info we can gather, the better. Was surprised to see how responsive you were to GFJ. Personally found that 16 oz of fresh squeezed GFJ only doubled the absorption rate (pasteurized GFJ, and piperine, for that matter, were completely ineffective)…interesting how everybody is different.

Wanted to ask a few questions since jumping in late here:

Seems like you were maintaining a regimen, at ~ 36ng/ml per week, approaching that prescribed for kidney transplant patients (who try to maintain an ~ 8 ng/ml trough minimum?). Was wondering what your half-life measurements were with and without GFJ (fyi, my half-life measurement, w/o GFJ, is an unusually short 41 hours)? Since you’re particularly sensitive to GFJ, it may be that it extends your half-life values even further (affecting not only first-pass, but second-pass metabolism)?

For future use, here’s a Google sheets link to a Rapamycin half-life chart (modified the original from a related forum here) where you can enter some variables to arrive at peak dose (e.g. if taken the night before) and half-life. (Rapamycins Half Life Graphs 1-2-23.xlsx - Google Sheets) You’ll have to download it first to enter your own data.

If you haven’t already, once you find your half-life measurements, you might want to try the same dose, but with a much longer/lower trough. Besides even more beneficial mTORC1 suppression, apparently another reason for higher peak Rapamycin blood levels (per Blagosklonny) is to better penetrate the blood-brain barrier and confer more benefit to our neurons (and overall brain function including all-important hypothalamic function).

Second question was, if you had considered Berberine as a substitute for Metformin—both of which reduce glucose production in the liver (and nearly identical in effect in every other metric except stomach discomfort)? It might help compliment the Acarbose which directly inhibits complex carbohydrate metabolism directly from a meal (post-prandial). Having control of both blood-glucose pathways might be of most benefit. Both Metformin, and more clearly, Acarbose have shown to have an additive effect with Rapamycin in previous ITP studies…something (per Dr. Miller) that is rare to find.

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#70

Hello BednarU - I appreciate your thoughtful message - I just got online. Was busy with family and gym.

You asked: Was wondering what your half-life measurements were with and without GFJ - I have only done Labcorp sirolimus testing at trough and 1.5 hours after does for t-max. However, at 10 days after dosing my trough was .7 ng/mL

There is the Blood Brain Barrier issue - and despite some on here going higher and higher - per Blagosklonny. I am thinking this isn’t working with my phenotype. Hence, I am going to reduce to 1/3 of 36 ng/mL-- even at that 12 ng/mL - it is plenty high. I will retest my biological age in 6 months and then plan my next steps.

Your second question: if you had considered Berberine as a substitute for Metformin—both of which reduce glucose production in the liver (and nearly identical in effect in every other metric except stomach discomfort)? As you noted Acarbose is clinically shown to extend life with rapamycin - so I am sticking with Acarbose that is very well tolerated by my gut - just a bit of gas.

Thanks for your inquires. It is all guess, test , tweak, test… looking for the sweet spot.

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#71

Thanks for the quick reply. Just plugged in your peak and trough values and it looks like you too have an unusually quick 41 hour half-life rate for Rapamycin. Now am wondering if that is more the norm than what has been previously reported…64 hours (+/- 16 hours) avg. for renal patients and even longer for non-renal patients with men having longer half-life rates than women. Not that we have a choice, but think a quicker half-life rate is more desirable, since you can achieve higher peaks without the exposure of a slow draw down.

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#72

I just had my annual “wellness” exam and I flunked!
My hemoglobin, hematocrit, and MCHC were low; 11.7 g/dL, 36.7%, 31.9 g/dL
This indicates some anemia.

I did talk to my doctor about rapamycin and he didn’t have a fit but is not about to prescribe any for me.
We discussed the probable causes of this problem. I told him I had given blood twice in the last year and he told me that my bone marrow doesn’t replace red blood cells as rapidly at my age and says that I am stressing my body giving blood this often. He also pointed out that rapamycin can cause anemia as a side effect.

He strongly suggested that I stop taking rapamycin for a while.
He suggested that I eat liver and other organ meats. In lieu of that, since I don’t like liver, etc., he suggested an iron supplement.

He has scheduled me for further and more frequent testing.

So I am taking at least a 3-month break from rapamycin. It will be interesting to me to see what my lipid levels, etc., revert to.

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#73

I’m not sure if it’s something your doctor could recommend, but you could see a hematologist for your low iron, especially if iron supplementation causes you stomach issues. My spouse sees a hematologist for her low iron and they give her an IV iron infusion, usually 2 treatments in 2 weeks.
In my opinion, this is a much better way to get your iron levels back up if you can do it. I don’t know if there are ramifications for doing it this way at your age, but if you could do it, you’d be back to normal iron levels in a few weeks vs a few months. Then you can resume your normal schedule and don’t donate blood at your age in the future! Especially since you’re on rapamycin which can cause anemia.

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#74

Thanks, I think he would schedule a hematologist for the future if my iron levels don’t get back up in a reasonable time. So far the iron supplement hasn’t caused me any issues.

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#75

Obviously Haemoglobin is low and the others follow on. It does seem to be a bone marrow issue rather than a rapamycin issue.

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#76

Isn’t low iron linked with extended lifespan?

Conclusion: iron squares the circle of life extension

It can be seen from all of the above that iron is a common theme in many if not most life-extension interventions. This can help make sense of the seemingly disparate mechanisms of extending life by slowing aging.

As noted, autophagy is essential for lifespan extension, and autophagy activation declines with age. Ultimately, this can lead to “the garbage catastrophe of aging”, in which imperfect removal of damaged molecules leads to the accumulation of cellular “garbage”. Much of this decline in autophagy may be due to lipofuscin, a substance that is relatively difficult to remove and which “gums up” the machinery of autophagy. Importantly, iron plays a key role in the formation of lipofuscin; iron can react with polyunsaturated fatty acids and other molecules to form this material, and iron accelerates lipofuscin formation in cultured human glial cells and rat cardiomyocytes [75]. Lower levels of iron could be expected to slow the rate of lipofuscin formation.

Inhibiting the cellular integrator of nutrients and growth, mTOR, leads to longer lifespan in virtually all experimental animals tested so far. We have seen that mTOR in turn plays a crucial role in the level of body iron stores; mTOR activation increases body iron, and iron in turn activates mTOR. That mTOR inhibition increases lifespan illustrates the fundamental trade-off between growth and longevity, and iron is a growth factor [76].

Many drugs and natural products extend lifespan by seemingly disparate mechanisms, but inhibiting iron absorption, or chelating (binding and removing) iron is a characteristic of many if not most of these substances.

Reduced iron stores can explain how calorie restriction extends lifespan.

Finally, iron can explain the free radical theory of aging. Iron catalyzes the formation of the most damaging free radical, the hydroxyl radical.

In sum, iron satisfies many of the conditions we might look for in a universally pro-aging substance. It accumulates with age; it is associated with many age-related diseases such as cardiovascular disease, cancer, and Alzheimer’s disease; it catalyzes the formation of cellular junk molecules and helps to prevent their turnover; removal of iron from plasma may be rejuvenating; and people with lower levels of body iron – blood donors – have a lower mortality rate.

Iron is intimately associated with aging, and control of body iron stores may be an important way to extend human lifespan.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8544343/#sec-5title

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#77

Thanks for sharing.

been 4 months on Rapa. I just got back results of Inside Tracker blood work – two of the areas flagged low were Ferritin and Transferrin saturation – Hemoglobin, RDW, MCH, MCHC, RBC, Iron, TIBC were all in normal range.

I do not donate blood, but have explicitly avoided any iron containing supplements for years due to concerns raise about it increasing cellular oxidation and possibly being pro-cancer . . . now debating whether to do a brief course of Iron supplement.

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#78

Super helpful – interestingly, in my blood results this week Ferritin and Transferrin Saturation were quite low, but all the circulating blood measures were normal . . . RBW, MCH, MCHC, etc . . .

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#79

If there isn’t an underlying cause for the anemia I think @PDM would argue that your lower levels are better from a longevity standpoint though I personally perform much better with higher levels of Hb

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#80

To an extent, yes. But they still need to be in the normal range and not chronically low. I’ve seen others on here talk about how getting your iron lower is good, and I agree to an extent. We can’t forget that iron helps build healthy red blood cells and is very important to your well being.

Your iron stores should never build to a level in which they are above normal ranges, that is also extremely unhealthy. There are lots of ways to get your iron lower if they go above normal. You can donate blood, your body then goes to work replacing the blood you donated which uses iron stores to help achieve that.
You can also regularly exercise, especially aerobically. Aerobic exercise beats up and damages your red blood cells because they are put to work providing oxygen to your muscles for energy. Prolonged aerobic exercise will cause red blood cells to be so damaged/fatigued that they will split, grow stronger, and healthier. That process takes iron as well.
A primary reason that women runners can become chronically anemic is because between lots of running and menstruation they don’t have enough iron stores to replenish their red blood cells.

One of the reasons I’m sticking to a lower dose of rapamycin is because I’m worried regularly putting myself into autophagy is going to make me more anemic since I exercise and run a lot.

It’s all a balance and we each have to find what works best for our lifestyles. You want your iron stores to be in the normal range. Too high or too low can be extremely dangerous.

1 Like
#81

Interestingly, I just found out from an article cited in another post:

“Acarbose extends lifespan in mice [47]. Acarbose increases fecal excretion of iron and has been known to be a cause of iron-deficiency anemia in humans”

“Thus, we can see that a large number of life-extending compounds also interact with iron, either by chelation, inhibition of absorption, or increased iron loss.”

Maybe just stopping Acarbose, which I have done, and rapamycin for a while will solve the problem. I agree with those who think iron accumulation in the body is dangerous to your health and longevity. I am just shooting for the low normal range.

“https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8544343/#sec-5title”

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#82

Iron: an underrated factor in aging

Dennis Mangan

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8544343/

" Abstract

Iron is an essential element for virtually all living organisms, but its reactivity also makes it potentially harmful. Iron accumulates with aging, and is associated with many age-related diseases; it also shortens the lifespans of several model organisms. Blocking iron absorption through drugs or natural products extends lifespan. Many life-extending interventions, such as rapamycin, calorie restriction, and old plasma dilution can be explained by the effects they have on iron absorption, excretion, and metabolism. Control of body iron stores so that they remain in a low normal range may be an important, lifespan- and healthspan-extending intervention.

Keywords: iron, aging, oxidative stress, calorie restriction, plasma dilution"

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#83

Could be both. Rapa dose could be too big for the age (or time in between too short). Just logically, at that age a more conservative approach is appropriate. Unfortunately there’s no research available re Rapa for different age groups. I know that the lowest possible dose works much better for me at 67 (especially I’ve been taking it for a long time and plan to continue for a long time as well).

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