Insulin Sensitivity Is A Hallmark Of Longevity

[@rfbead321]

Most excellent presentation. Thumbs Up!

[@conqueragingordietrying123]

Thanks rfbead321!

[@olyav5819]

Good video! Thanks! Waiting for the part 2.

[@ramiv9953]

Uh hello Dr. L, Could you still remember about the 8 am 1pm time window of eating video you did? I lost sight of it and have watched too many of your videos to know which it is.

[@conqueragingordietrying123]

Hey ArchBack, I don't remember which video that I said that either, but my eating window is closer to 6AM to < 3PM. That doesn't mean no food after 3PM, but I try to keep it very light, < 100 calories after 3PM. Most days I'm successful with that, but some days I eat a more than that after that time. With this eating schedule, I wake up less to pee, and my sleep quality is much improved. I don't think it's impacted my systemic biomarkers, though, in contrast with the published literature.

[@littlevoice_11]

The concept of insulin resistance is not well understood and emerging research shows that insulin sensitivity can vary from tissue to tissue during a fast and depending on an individual's macro ratio. For example a low carb I.F. individual can expect to have some peripheral or muscular insulin resistance which is thought to be a temporary effect that may even be beneficial. I think it is also interesting to look at insulin sensitivity in relation to circadian rhythm and how this changes over time. A really interesting field. Anyway, thank you for sharing today's video. I always look forward to your videos and your responses to comments

[@neilchristensen538]

Very interesting. Thanks!

[@edwhite2255]

This begs the question on if the long lived low insulin folks achieved this outcome through genetics, diet, exercise or some combination

[@conqueragingordietrying123]

Definitely, Ed, good point.

[@thomastoadally]

Thanks again Dr. caloric restriction or an intermittent fast, seems to not overwork the body. Helps to keep glucose levels down. Thanks again 👍👍👍

[@ChuckFrasher]

A studio was posted showing that the CR mice who were fed once per day did much better that CR mice who ate the same food, same calories but ate throughout the day. Same food, same calories. …. Showing that it was the fasting that created greater health and life span.

[@conqueragingordietrying123]

Yes Chuck, that video is here: kzbin.info/www/bejne/rpywin2paa-gjqc

[@ChuckFrasher]

@@conqueragingordietrying123 Thank you so much!

[@larsnystrom6698]

I'm more interested in what Methionine restriction can do. CR might work for mice, but it's not so easy -- nor beneficial -- for humans. Methionine restriction seems to mimic CR! And it's more feasible in humans. I think it's the higher Methionine level in meat compared to in plant which makes vegitarians live longer -- if they can avoid the deficiences inherit in that diet. Now, it also seems that Glycine makes the problem with high Methionine go away! So, it's not really Methionine Restriction, but Glycine deficiency that's the problem! And that's really something humans can do something about! I would like to see Methionine/Glycine trials on mice life- and healthspan, instead of CR. Although, I think the mice shouldn't be fed ad librium, ever! Methionine affects both Homocysteine and Insulin. So those are the main suspects in this story. Possibly a driver of insulin resistance and type 2 diabetes. Methionine restriction (MR) and hepatic protein tyrosine phosphatase 1B (PTP1B) knockdown both improve hepatic insulin sensitivity by targeting different proteins within the insulin signaling pathway, as well as diminishing hepatic triglyceride content through decreasing hepatic lipogenesis.

[@nicholassteel5529]

Nice presentation. Thanks✌️

[@andrewf.7813]

Excellent!

[@conqueragingordietrying123]

Thanks Andrew F!

[@andrewf.7813]

Really motivated to keep focused on diet/exercise/sleep and try and stay low-ish carb

[@PaulBeauchemin]

Excellent information

[@KJ-um1gq]

Doc, what are the best ways to measure insulin sensitivity? I've had my C-peptide tested several times, which is an insulin proxy, and it's always on the lower end of the normal range. I've test my A1C several times as well, never had a measurement over 4.9.

[@conqueragingordietrying123]

Aside from what's best, I try to keep it simple0-insulin and glucose are definitely better than glucose alone. That said, C-peptide and HbA1c are also good measures.

[@Caldermologist]

I certainly would not assume insulin sensitivity decreases in the very old. Surely it is more likely those who get really old know how to stay healthy? It is actually very simple. The information required is available for most people, but apparently never for medical doctors. A video explaining how each of us on our own can avoid getting diabetes, or any of the deseases of affluence, would be more useful, but since you never explained why insulin sensitivity is created anyone looking for useful information has to look elsewhere.

[@Kevin-ey8pj]

What was especially interesting to me was the increased lifespan from the growth hormone knockout mice. I always thought growth hormone was beneficial-- it's often touted as a benefit of fasting.

[@conqueragingordietrying123]

There's likely a U shaped curve for GH in people, too. Too much or too little, shortened lifespan.

[@Kevin-ey8pj]

@@conqueragingordietrying123 Thank you so much for the response! So this means the KO mice did produce GH, just less?

[@conqueragingordietrying123]

@@Kevin-ey8pj Ha, I almost always try to respond. I'm not a fan of sites that put out content but don't respond-i think that's disrespectful! In Fig.6 of this paper, GH expression was reduced by 80%, but not completely eliminated, in the GHRH KO mice: pubmed.ncbi.nlm.nih.gov/15155578/

[@bobbobson4030]

@@conqueragingordietrying123 Don't Ames dwarf mice (don't produce GH) hold the record for mouse lifespan?

[@conqueragingordietrying123]

​@@bobbobson4030 Ames dwarf mice are definitely among the longest lived group-whether CR in certain genetic backgrounds beats the lifespan extension in Ames dwarf mice, I'm not sure.

[@MrGatward]

Thanks Michael - a bit off topic, I’m a bit confused about the relationship between TMG and methionine. I want to keep my methionine low for longevity but I’m also thinking of taking TMG to keep methyl groups in balance while taking NR to test if it improves liver markers.

[@MrGatward]

Does TMG increase Methionine endogenously?

[@conqueragingordietrying123]

Hey Tom, I wouldn't just measure liver markers, but the CBC+standard chemistry panel+hs-CRP, so that you can calculate biological age with Levine's test and aging.ai. Then, you can see if TMG and/or are net beneficial on your biomarkers and biological age.

[@MrGatward]

@@conqueragingordietrying123 Will do, cheers

[@dr.julia-heyakarcic8862]

Please produce a video on leptin , lifespan etc. see Ivor Cummins Ron Rosdale MD interview.

[@conqueragingordietrying123]

Thanks Dr. Julia-Heya Karcic. I try to focus on biomarkers that are are quantified by most people first, then I'll eventually get into markers like leptin, adiponectin, etc.

[@squarz]

If I understand correctly mice were KO by genetic inducted mutation? Why this is not a natural mutation then? It has to have a lot of downsides, at least for mice, but maybe not for humans? We tend to live a lot different from rodents, we don't need to mass reproduce and grow in a few months, we are one of the slowest growing mammals am I right? What can prevent us to think that humans already have this kind of mutation or are naturally more similar to a KO mouse? There is a study beforehand about the all the data on humans and mice or it's simply a faster way to try different things?

[@christopherbrand5360]

It does not improve reproductive fitness

[@conqueragingordietrying123]

Hey squarz, while GHRH KO mice are discussed in the video, the main point is that a contribution to their longevity also involves insulin sensitivity.

[@squarz]

@@conqueragingordietrying123 Yeah. I get it, don't get it wrong I found the video really interesting. I thought the main focus of your videos was about the not known or discussed things and we know as a fact that insulin sensitivity and resistance are a big factor in healthspan and lifespan while we don't know a lot about GH, FGF21 and such.

[@nemanjababic7141]

Thanks! Did you find the optimal range of insulin and homo-ir levels w.r.t ACM? For H1ABC which is in %, for the time being I was thinking of deriving it based on glucose reference of 80-94 mg/dL. If H1ABC is between ~4.4-4.9% it means that on average over the past ~3months the glucose levels was 80-94 mg/dL. If I am interpreting it correctly.

[@conqueragingordietrying123]

For insulin, it's a bit complicated-it increases, then decreases during aging, most likely as an age-related failure of beta-cells to produce insulin. With that in mind, low insulin in advanced age could be a sign of insulin sensitivity or beta-cell exhaustion-there's no way to know by only measuring insulin. So I wouldn't pay much attention to HOMA in people of advanced age.

[@dpqd1]

I was aware that CR is good for long lifespan, but how one could measure insuline sensitivity at usual home condition. What devices do you recommend?

[@conqueragingordietrying123]

I wish it was that simple for insulin measurement at home. For now, blood testing is how I get it done, but it's an extra test with an additional cost. It's not on the standard chemistry panel.

[@gemagel20]

@@conqueragingordietrying123 Thanks Michael for the video. What is this extra test you are referring to? how can someone ask for this? Insulin sensitivity test?

[@conqueragingordietrying123]

@@gemagel20 Hey gemagel20, insulin is not normally measured in the US on a standard chemistry panel, so it's an "extra" test in that one has to ask their Dr to include for a yearly physical. Alternatively, it can be ordered directly online.

[@framexdd]

Do you take metformin? It has been show to increase life span and has been shown to be safe even in the healthy

[@conqueragingordietrying123]

Based on the data in the video, one would expect metformin to have a significant effect on lifespan. However, its effects on lifespan are mixed, and doesn't beat CR or rapamycin for their lifespan extension length. I don't take metformin, but I'm not opposed to it if my approach stops working.

[@conqueragingordietrying123]

@@CraigHocker I haven't seen that data, but if you have the paper link, please post it!

[@jackbuaer3828]

@@conqueragingordietrying123 I am not aware that CR has been shown to have a significant effect on life span in long lived species, such as humans. It may be good for extending life in yeast, mice, and other short lived species. It may also be good for improving biomarkers in longer lived species, but the monkey studies seem to imply that it does not result in significant life span extension.

[@conqueragingordietrying123]

@@jackbuaer3828 The jury is out on CR for lifespan extension in people, but arguably one of the biggest factors that impacts health is calorie intake.

[@framexdd]

@@conqueragingordietrying123 there is also skq1 and that's op for longevity... most powerful anti-oxidant 😱

[@FelipeMartinez-ce1bt]

Is the centenarian's reduced insulin sensitivity a result of less circulating growth hormone in them (or maybe less growth hormone receptor sensitivity due to genetics) or because of eating less than people that didn't live that long.

[@littlevoice_11]

What would be the ideal blood glucose or hgA1c for anti aging based on your research? Dr Perlmutter shared some research a while ago on brain atrophy at blood sugar suggesting the lower the better. Some suggest 3.3 for fasting and 4.6 for optimal when on a low carb diet

[@bobbobson4030]

Are there any studies exploring if HOMA is a better predictor of all cause mortality than fasting glucose?

[@conqueragingordietrying123]

That's definitely on my to-do list, a probable video, at some point. Note that on yesterday's blood test (blood test #1 in 2022), I measured insulin for the 2nd time within the past 8 months, and I'll probably measure it for every test going forward. That should say something about how much I value insulin sensitivity.

[@Battery-kf4vu]

That tells us that blunting GH should be a powerful factor for longevity. However, the problem is that if one reduces calories, GH is going to go up, so this should partially counteract the longevity effect that could be gotten. So how could one both do CR and keep GH at the same level or lower it the same time? While at the same time keeping the joints and collagen as healthy as possible.

[@conqueragingordietrying123]

*in sedentary mice. In humans, there's a balance between low GH and quality of life. Conversely, I'd bet that very high levels of GH limit human lifespan, too. It's tough to say what the sweet spot is, especially since IGF-1 (whose expression is induced by GH) decreases during aging.

[@Battery-kf4vu]

@@conqueragingordietrying123 I wonder if centenarians have lower GH than normal. And also if the KO mice were able to exercise or if their joints and muscles were too weak. As for the okinawa diet, IIRC some have speculated that the potatoes they were eating were rich in hyaluronic acid. perhaps they had less than average GH, which helped their longevity, but compensated with more HA.

[@conqueragingordietrying123]

@@Battery-kf4vu Based on IGF-1 levels, one could argue that they do have relatively low GH. However, that comes with the consequence of low muscle mass and function, which GH and IGF-1 positively impact.

[@rfbead321]

@@conqueragingordietrying123 Well, I'm certainly not interested in being old and weak. Better to die running uphill!! So for me, a high protein keto-ish diet with resistance training, good sleep, and low stress is the n=1 equation.

[@kkostadinof]

@@rfbead321 You should have your wish granted then. High protein= increased growth signalling= shortened lifespan. Prepare for lifespan 70-85 yrs max depending on other factors.

[@ChillFantasticFive]

What are all the tips to increase insulin sensitivity? Vegans have better insulin sensitivity than vegetarians which have better insulin sensitivity than omnivores. Studies show certain saturated fatty acids make decrease insulin sensitivity but not MCT. Refined carbs are bad for insulin sensitivity. CR as mentioned is great for insulin sensitivity as is exercise. Any other researched tips? Main web pages on the subject dumb it down and miss the important details. I'm not a vegan but recent research is making me eat less meat and more legumes.

[@conqueragingordietrying123]

Hey Brian, rather than me making a blanket statement about what improves insulin sensitivity (it can vary individually), using glucose levels as a proxy, here's what may work for me (besides exercise, CR, etc.): kzbin.info/www/bejne/noHQqWV3hLSHbbc

[@littlevoice_11]

I would be interested in your thoughts on time restricted eating on insulin sensitivity. I have sen research that time restricted eating such as 16:8 and OMAD improve insulin sensitivity and I would assume therefore reduce HgA1c. But other studies show that during the calorie consumption window, due to large number of calories consumed in one go there is a larger blood glucose spike (despite lower insulin and blood sugar during the fast). So I wonder if this is true and if it is equally important to consider the glucose variation as average blood glucose and insulin levels to maintain it.

[@littlevoice_11]

@@conqueragingordietrying123 what is your usual range if 130 is your upper limit? Muscle mass and age probably allow for a greater carb flexibility. Its inspiring to hear your healthy goals. Have you considered posting a video of a day in your life including 'what I eat in a day's timings and supplements showing how you implement what you learn.

[@conqueragingordietrying123]

@@littlevoice_11 I spent most of the day < 90 mg/dL. the longer the fast, the longer the glucose decline. So if I stopped eating at 2PM and has a glucose of 130, within an hour (or 2) it was down to the 90s, and then in the 75-90 range before bed (~10PM). I'm glad to help, Little Voice, and the day-in-the-life video may be coming sooner rather than later. I may link that with my next blood test data in a few weeks.

[@diamond_s]

wonder how this fares with ketosis, as I've heard that yields momentary(temporary) insulin insensitivity. Also wonder given amla drastically reduces blood glucose, is it increasing insulin sensitivity?

[@conqueragingordietrying123]

Mice on a high fat, ketogenic diet have an increased lifespan, but I haven't looked into their insulin sensitivity status. That's a possible Part II for this series!

[@markveen1373]

Amla? I use cinnamon everyday, from breakfast to teas. Same effect?

[@conqueragingordietrying123]

@@markveen1373 The best way to assess that is with blood test data for your own insulin and glucose. Just because amla or cinnamon works in a study doesn't mean that it will work for you, we have to individually test to identify if it works for us (or not).

[@diamond_s]

@@markveen1373 probably, it might have synergistic combination effect. Not sure how strong is cinnamon, when I tried it didn't seem that strong. Will see how it goes with amla, whether amla is as strong as some of the claims go.

[@markthornton9128]

Does this mean HGH is related to having diabetes?

[@conqueragingordietrying123]

Is HGH linked with insulin resistance?

[@newdata]

how can one volunteer to be KO human ?

[@conqueragingordietrying123]

People can altering their hormone levels to change gender, so I can't see why someone who wants to ablate their GH levels couldn't also be possible.

[@donaldwashington9017]

Who are you talking to? Is this a medical class.

[@conqueragingordietrying123]

Hey Donald Washington, I'm talking to everyone that's interested in these topics. Whether that's a medical crowd, people interested in slowing aging, all are welcome!

[@jamesnguyen7069]

this is actually similar to how people become resistant to weed ( the thing people smoke in california)