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Old 09-05-2012, 11:05 AM   #1
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Article: SIRT-1 may protect us from diabetes

Another reason to encourage us to do those JUDDD rotations folks. Get that SIRT-1 activity going to your benefit as strongly as possible!

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Article Date: 09 Aug 2012 - 1:00 PDT

Protein That Slows Aging May Protect Against Diabetes

A new MIT study has found that a protein that slows aging in mice and other animals also helps fight against the damages of a high-fat diet, including diabetes.

Over a decade ago, SIRT1's longevity-boosting properties were discovered by MIT biology professor Leonard Guarente, who has continued to examine its role in various body tissues. His recent study, appearing August 8th in the journal Cell Metabolism, observed what happens when the SIRT1 protein is missing from adipose cells, which make up body fat.

The research team put mice on a high-fat diet and realized that they started to develop metabolic disorders, like diabetes, when they lacked the protein, while normal mice given the same diet did not develop these disorders as quickly.

Guarente, the Novartis Professor of Biology at MIT, explained:

"We see them as being poised for metabolic dysfunction. You've removed one of the safeguards against metabolic decline, so if you now give them the trigger of a high-fat diet, they're much more sensitive than the normal mouse."



This finding suggests that drugs that enhance SIRT1 activity could possibly help fight against obesity-linked diseases.

While the expert studied yeast in the 1990s, he first discovered the effects of SIRT1 and other sirtuin proteins. These proteins have since shown to help keep cells alive and healthy by coordinating a variety of hormonal networks, regulatory proteins, and other genes.

In order to pinpoint the gene's effects more accurately, Guarente and his team deleted the gene from organs such as the brain and the liver. Their past research has shown that in the brain, SIRT1 protects against the neurodegeneration seen in Huntington's, Alzherimer's, and Parkinson's diseases.

SIRT1 is a protein that is known for removing acetyl groups from other proteins while modifying their activity. According to Guarente, the possible targets of this deacetylation are numerous, allowing SIRT1 to have its broad range of protective powers.

The hundreds of genes that were turned on in mice that were fed a normal diet lacking SIRT1 were analyzed by the team. They found that they were almost identical to those genes turned on in normal mice that were given a high-fat diet.

These results suggest that the development of metabolic disorders is a two-step process in normal mice. He said, "This first step is inactivation of SIRT1 by the high-fat diet, and the second step is all the bad things that follow that."

The scientists wanted to investigate how this occurs and discovered that in normal mice fed a high-fat diet, the SIRT1 protein is cleaved by an enzyme (caspase-1), which is induced by inflammation. They were already aware that inflammation can develop from high-fat diets, though it is still unknown how that exactly happens.

Guarente said:

"What our study says is that once you induce the inflammatory response, the consequence in the fat cells is that SIRT1 will be cleaved."



As normal mice grew older, the researchers discovered that they became more susceptible to the effects of a high-fat diet than younger mice, showing that the protective effects of SIRT disappear as they age. Knowing that inflammation increases with age, Guarente is now researching if age-related inflammation also provokes SIRT1 loss.

Written by Sarah Glynn
Copyright: Medical News Today
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Old 09-05-2012, 01:02 PM   #2
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Interesting article. Thank you for sharing.
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Old 09-05-2012, 04:01 PM   #3
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Fascinating reading.

Interesting that this research hinges almost exclusively on the damage a diet too high in fats can do. I was unaware that too-high fats were such a specific cause of inflammation and, by extension, fought the SIRT-1 gene so.

Pat, do you think the last few sentences tell us that a person will benefit from supplementing with Resveratrol more as they age?
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Old 09-05-2012, 04:13 PM   #4
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Fascinating reading.

Interesting that this research hinges almost exclusively on the damage a diet too high in fats can do. I was unaware that too-high fats were such a specific cause of inflammation and, by extension, fought the SIRT-1 gene so.

Pat, do you think the last few sentences tell us that a person will benefit from supplementing with Resveratrol more as they age?
Well, I know we latch onto all of this if there is so much as a hint of promise, but all I know is that most of my people live well into their late 80's and are still strong and robust in those late years, and DH's people on both sides live way beyond that.. into 90's and one beyond 100. But none of them took Resveratrol. Or any other supplements that I am aware of. They just ate plain ordinary foods, but they didn't limit the veggies and fruits, so did get a lot of vitamins there, and I think they included organ meats in their diets because many farmed back then and butchered their own animals. I can't imagine that they didn't make use of the whole animal that they butchered. But I think there were concord grapes grown. I know grandma made her own grape jelly with her own grapes. Lots of table sugar in there too!

So who knows? Like I said, we seem to latch onto any hint of help. Maybe in another half century they'll be able to tell us absolutely.
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Old 09-06-2012, 03:56 AM   #5
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Thanks for posting this article.
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Old 09-06-2012, 04:38 AM   #6
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From my experience, my blood sugar has never been better than it is on juddd.
Over the summer I was off plan and it was higher, now that I'm back on plan it's really good, usually in the 70-85 range (rarely over 100 - I think it was 120 after a pasta and garlic bread meal with wine!).
So I'm sold that there's something to the UD/DD eating, even if it's carby.
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Old 09-06-2012, 06:10 AM   #7
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From my experience, my blood sugar has never been better than it is on juddd.
Over the summer I was off plan and it was higher, now that I'm back on plan it's really good, usually in the 70-85 range (rarely over 100 - I think it was 120 after a pasta and garlic bread meal with wine!).
So I'm sold that there's something to the UD/DD eating, even if it's carby.
I believe that too, Dottie. There is something about doing those strong rotations that brings a body back to operating like it was meant to, once again. I don't question that, even though I think it is really amazing. I think the people who really do JUDDD reap some of the most important benefits to their health they could ever imagine!

I know I'm going to keep with this plan. I've never felt better!
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Old 09-06-2012, 06:13 AM   #8
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As normal mice grew older, the researchers discovered that they became more susceptible to the effects of a high-fat diet than younger mice, showing that the protective effects of SIRT disappear as they age. Knowing that inflammation increases with age, Guarente is now researching if age-related inflammation also provokes SIRT1 loss.
I don't think I stated that question well. What I mean is that if the "protective effects of SIRT disappear" as normal mice age, I wonder if the addition of Resveratrol (or pterostilbene or other in the future) will be recommended less for younger people and more for older, who may have passed a point of the "SIRT-1 loss" mentioned at the very end of the article. It would be interesting if researchers might someday make a recommendation for taking supplements according to age.

I guess another question this would bring up in my mind for the researchers - what is meant by "SIRT-1 loss" in the article. Is there actual loss of SIRT-1 at some point in these normal mice's lives? Or is that just not stated well in the article and there is just loss of its protective effects, which, to my mind, could be affected by supplements.

I don't take a supplement aimed at SIRT-1, but this article makes me think that someday I'd be wise to start.
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Old 09-06-2012, 06:34 AM   #9
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My standard response: Who knows?

Well, I'm pretty casual about jumping in response to any of these single reports anyway. I just find them all interesting and file away the info, for what it may be worth, in my head with previous reading I've done. As they say, we're not mice. Some things seem to affect us the same and some things just don't. For example, the diet they fed these mice... They were fed a high fat diet. I don't eat a diet that is high in fat. I get plenty of it to my way of thinking, but I'm higher in vegetables and fruits (carbs) than I think these lab rats were fed.

I found the following interesting in regards to the high fat diet as it pertains to all of this:

"..........These results suggest that the development of metabolic disorders is a two-step process in normal mice. He said, "This first step is inactivation of SIRT1 by the high-fat diet, and the second step is all the bad things that follow that."

The scientists wanted to investigate how this occurs and discovered that in normal mice fed a high-fat diet, the SIRT1 protein is cleaved by an enzyme (caspase-1), which is induced by inflammation. They were already aware that inflammation can develop from high-fat diets, though it is still unknown how that exactly happens.........."


I'm 69 years now. I eat a diet that has some of everything and not too much of anything. I'm not a low carber, and my diet isn't a high fat diet, although like I said.. I think I get more than enough fat. I'm not very big on *supplements* and am not taking supplements outside of Vit D3, since I don't seem to spend much time outdoors making my own D.

I don't know, Whitlin'. I sure would like to know more about the inactivation of SIRT-1 by the high fat diet!!!!! That surprised me.

Last edited by SoHappy; 09-06-2012 at 06:37 AM..
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Old 09-06-2012, 06:54 AM   #10
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... I sure would like to know more about the inactivation of SIRT-1 by the high fat diet!!!!! That surprised me.
Hmmm, I would, too. It's all way over my head and while I'm new to JUDDD and liking it very much, I am a high fatter, very low carber and wonder if I'm pitting one against the other (JUDDD and high fat), as far as the SIRT-1 gene is concerned.
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Old 09-06-2012, 07:29 AM   #11
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Hmmm, I would, too. It's all way over my head and while I'm new to JUDDD and liking it very much, I am a high fatter, very low carber and wonder if I'm pitting one against the other (JUDDD and high fat), as far as the SIRT-1 gene is concerned.
Here's part of the problem. These studies are important and interesting. And I'm pretty sure more and more is being learned as the studies progress and the years go by. But the articles written are brief and, as this one illustrates, offer only a tidbit by a writer who wasn't even in on the study.

Their stated finding was that normal rats, fed a high fat diet, eventually developed internal inflammation which caused an increased caspase-1level, which 'cleaved' the SIRT-1 protein, thus causing the loss of its protective ability, apparently.

But.. what was this diet? What fat percentage? What fats? We aren't told.

My own personal thought is that a diet very high in fat and very low in carb isn't what would be considered natural to man as he lived across the continents of this world. I've eaten a lot of wild game animals, and none of that meat is very fatty. Most of it is very, very lean and in need of the addition of a lot of fat in cooking to my way of thinking! My thought is that primitive man hunted and gathered.. whatever they could get their hands on. That would include roots and bulbs, shoots and leaves, seeds from the grasses and nuts from the trees, buds and blossoms and fruits.. as well as any living creature of any size that they could grab or kill. But most wild creatures just aren't very fatty. So I just don't think our primitive ancestors ate an especially high fat diet.

And I do know that my thoughts aren't shared by many here. I guess I'm sort of a maverick.

But, you know.. we all just get to eat the diet we want to. What makes us feel the best? What gives us energy and vitality? And Joy?

All I know is, I'm not eating a high fat mouse diet!
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Old 09-06-2012, 08:01 AM   #12
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I did want to focus on this one paragraph too, of the protection active SIRT-1 protein brings for a healthy brain!

"..........In order to pinpoint the gene's effects more accurately, Guarente and his team deleted the gene from organs such as the brain and the liver. Their past research has shown that in the brain, SIRT1 protects against the neurodegeneration seen in Huntington's, Alzherimer's, and Parkinson's diseases.........."

I'm never going to stop JUDDDing, that's for sure!
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Old 09-06-2012, 11:00 AM   #13
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I just want to share my experience doing JUDDD eating low carb/high fat. First off I was eating very high calories because it doesn't fill me. Didn't lose wt(even though I'm in maintance). Started gaining. I was doing it because I thought it was good for me. Well I did not like how I felt. It's hard to describe other than I just didn't feel right. Out of balance, buzzing, almost like your on something. I was having sleeping issues(don't know if that's related). Mood swings.
I've now decided to just do juddd and worry about the calories. Not low carb or high fat or how much protein or anything else! Just good 'ol juddding! I've been keeping to my calories, eating fruits, veggies, bread oatmeal, meat. Anything. But staying with my calories.
I feel SO much better. My wt is going back down. I feel satisfied with what I'm eating. Mood is more calm. Sleeping better.
I would be interested to hear if anyone else has tried to eat high fat while on juddd and how they felt.
It may be different for others.
Just thought I'd share since high fat was being discussed.
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Old 09-06-2012, 11:09 AM   #14
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Pat-a lot of things you say really help me. I think you are right. I don't think it is natural to eat so high fat. The way you describe what you eat, enjoying all the foods that nature provides us just sounds the most natural to me.
Also you mentioned in another thread about vitamins and getting most of what you need from what you eat. I really like that.

Thanks for all your wisdom. I really value it!
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Old 09-06-2012, 11:32 AM   #15
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Very thought provoking article. Thanks for posting it.

I'm like you. I do not eat a high fat diet. But, I get plenty of it. I just don't consider it high fat. (Saying this after I made the most delicious egg noodle dish yesterday with melted butter and cheese.).

I think the JUDD WOE would prevent the overeating of too much fat because of the alternate day fasting. You can't eat "too much" fat and have a fast day IMHO.

I love reading articles about the benefits of SIRT1, especially the newer ones. (Even if they do keep talking about mice.)

The Horizon video was really great. The studies in that documentary are all being done on humans. They had real people fast and then did blood work. I especially liked the ADF lady and her findings that you really can eat whatever you want (low carb, low fat, high carb, whatever) on the UD as long as you don't over eat and as long as you stick to the DD fast or 500 calories.

And, Pat, I'm with you. I feel better than ever since I jumped on the JUDD wagon. I just don't get sick or tired, ever. I look healthy, feel healthy and happy and don't succumb to stress about anything, anywhere, any time. It's pretty cool living this way and keeping my weight in check at the same time!
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Old 09-06-2012, 01:16 PM   #16
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Old 09-07-2012, 12:21 PM   #17
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Fascinating reading.

Pat, do you think the last few sentences tell us that a person will benefit from supplementing with Resveratrol more as they age?
Better drink red wine just in case
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Old 09-07-2012, 12:26 PM   #18
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I just don't get sick or tired, ever.
Oh! I rarely get sick, but I wish I could say I don't get tired! I am tired RIGHT NOW. But I haven't been doing JUDDD as long as you or Kissa, either. Maybe there's hope for the future
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Old 09-07-2012, 01:54 PM   #19
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Better drink red wine just in case
lol maybe mega doses
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Old 09-08-2012, 07:23 PM   #20
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I was freaking out a little bit over this article, because I'm diabetic, so I can't eat too many carbohydrates and I've also read that I shouldn't eat too much protein; now I shouldn't eat fat, either? What's left; photosynthesis?!!!

But then I started looking around, because I remember reading something a while back about the high-fat diet fed to lab rats/mice; I haven't found it yet, but IIRC, this is the gist of it: originally, it was designed to eliminate Omega-3s, in order to see how that would affect the animals. And for some reason, other studies started using this formula (simply, some sort of oil--perhaps even something horrendous, like mineral oil--poured over their regular rat chow; not foods or fats that rats would naturally eat) for ALL studies involving fat.

And another thing to consider is that a high-fat diet is UNNATURAL for rats,
and that may be why they are experiencing inflammation;
this is without even considering what TYPE of fats are being used.
It's been pretty well established that excess Omega-6s can cause inflammation,
while Omega-3s can reduce it.

I respect that Pat & others may consider that the high-fat diet is unnatural for humans, too. But, this seems to me to be the most important sentence in the study:
Quote:
...the SIRT1 protein is cleaved by an enzyme (caspase-1), which is induced by inflammation.
Humans may have different inflammation triggers than mice, you know? Even if the mice were being fed high-quality fats that don't cause inflammation in humans.

Excerpt from the Fat Head site that made me lol:
"The Lipid Hypothesis became accepted partly because when researchers fed rabbits lard and cholesterol, the rabbits rapidly developed heart disease. Well, go figure … rabbits rarely attack pigs and eat them. When other researchers tried the same experiment on dogs, they couldn’t induce heart disease, no matter how much lard they fed them. So they concluded that dogs don’t get heart disease. But they do – if you feed them grains."
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Old 09-08-2012, 07:59 PM   #21
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I was freaking out a little bit over this article, because I'm diabetic, so I can't eat too many carbohydrates and I've also read that I shouldn't eat too much protein; now I shouldn't eat fat, either? What's left; photosynthesis?!!!

But then I started looking around, because I remember reading something a while back about the high-fat diet fed to lab rats/mice; I haven't found it yet, but IIRC, this is the gist of it: originally, it was designed to eliminate Omega-3s, in order to see how that would affect the animals. And for some reason, other studies started using this formula (simply, some sort of oil--perhaps even something horrendous, like mineral oil--poured over their regular rat chow; not foods or fats that rats would naturally eat) for ALL studies involving fat.

And another thing to consider is that a high-fat diet is UNNATURAL for rats,
and that may be why they are experiencing inflammation;
this is without even considering what TYPE of fats are being used.
It's been pretty well established that excess Omega-6s can cause inflammation,
while Omega-3s can reduce it.

I respect that Pat & others may consider that the high-fat diet is unnatural for humans, too. But, this seems to me to be the most important sentence in the study:


Humans may have different inflammation triggers than mice, you know? Even if the mice were being fed high-quality fats that don't cause inflammation in humans.

Excerpt from the Fat Head site that made me lol:
"The Lipid Hypothesis became accepted partly because when researchers fed rabbits lard and cholesterol, the rabbits rapidly developed heart disease. Well, go figure … rabbits rarely attack pigs and eat them. When other researchers tried the same experiment on dogs, they couldn’t induce heart disease, no matter how much lard they fed them. So they concluded that dogs don’t get heart disease. But they do – if you feed them grains."
I LOLed at the photosynthesis comment.

I've noticed before, too, that we are never really told what test subjects are actually fed, be they mice or men. So when we're told a diet is a *high fat* diet.. how high? What percentage from fat? And as you point out, what fats?

I do also think you have a good point when pointing out that a mouse's natural diet is most often not terribly high in fats, but is strongly vegetarian leaning and little carnivorous. So while a field mouse might munch on a grasshopper if he got his little mitts on it, chances are he's eating more roots and seeds, etc.

I always find the various studies interesting. I'm glad they've been looking into this SIRT-1 protein more and more. I didn't worry as much about what the diet was for the mice as I was interested more in the what happened when SIRT-1 was turned on or off. Regardless of what the mouse's natural diet is, I found it interesting that even when they were fed the fat, if they had an active level of SIRT-1 protein working for them, they were protected against the ills that befell those mice who had SIRT-1 *deactivated* and suffered consequences.
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Old 09-09-2012, 10:24 AM   #22
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I would be very interested in seeing the makeup of the "high fat" diet. LOTS of studies skew things and then you have the "interpretations" to deal with. I'm thinking of the rats in the China study. They were exposed to massive quantities of a known carcinogen and then given a protein isolate that promotes cancer. In the end the high protein rats had a higher incidence of cancer but all 30 of the high protein rats lived compared to only 12 of the low protein rats surviving. Vegan's like to tout this as proof that eating meat gives you cancer. I see it as proof that a low protein vegan diet is 66% more likely to kill you...

As for lean game meats, our ancestors, many 'traditional' meat eating tribes and most predators eat the organ meats first which are high in the essential fatty acids. As for other studies, I remember one about a group of settlers that tried to live off rabbit meat with very poor results because of how lean it was. Then there was a study using a high fat diet (87%) given to mice with type 1 and type 2 diabetes what were in renal failure that showed improvement in renal function. Of course ketogenic diets, which are typically high in fat, were used to treat epilepsy in children before drugs came out. In fact ketogenic diets are seeing a resurgence in that area as people are starting to shy away from drugs.

Then there are all the anecdotal reports of people on Atkins type diets that show a marked improvement in blood work after adopting a low carb diet.

Everyone is a little different but based on everything I've learned reserching my medical problems for the last few years and losing 75lbs at the same time I've come up with some general guidelines.

Protein - Between .8 and 2.0g per kg of ideal body weight. *Extreme weight lifters may need more.
Carbs -
Very LC <.3g per kg of ideal body weight
LC .3 - .7g per kg
Normal carbs .7 - 1.2g
Fat - Balance of calories. Should come from varied sources throughout the week/month.

Carbs and Protein are 4 cal/g and fat is 9 cal/g.

Highly insulinogenic foods should be avoided - these include sugar, HFCS, refined and processed grains, etc.

Additionally, mixing highly insulinogenic foods with fats should never be done. Some foods are naturally high in fat as well as being highly insulinogenic. Doughnuts anyone?

There's still a lot to learn but when these studies come out and they are less than transparent it does nobody any good IMO.
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Old 09-09-2012, 10:41 AM   #23
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Many of us here aren't concerned about the diet, fat levels, etc. of the test subject animals, other than that it caused the animals a poor health result, but rather the effects from inactive or activated SIRT-1 proteins. So regardless of the diet of test subjects, it's of interest to some of us to see whether SIRT-1 was protective for that test subject.. I'd say of even more interesting if the test subject ate a poor diet than if it had been eating its perfect natural diet.

Everyone here gets to eat however they choose to. We don't care what anyone else eats. But we're usually pretty interested in the effects of activating SIRT-1 through calorie restriction, regardless of what somebody chooses to eat in their diet.

As PirateJenny pointed out, a high fat diet isn't natural for a mouse. It caused them ill. Our interest is in the protective powers of SIRT-1, and the hope that it can also be protective for us as regards our many human ills.
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Old 09-09-2012, 07:56 PM   #24
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But they use mice for a reason and it's not simply to avoid PETA; they are omnivores and have similar enzyme/digestive capabilities/reactions including glucose/ insulin.

LC'ers tend to be so convinced that high fat is the best!! that it is hard to see beyond that and as soon as someone mentions lowering fat.....well, you know.

That said, I am assuming that the mouse fodder was reduced (unchanged otherwise) and fat was added to make up the cals.
So it was not a study of LCHF but just high fat w the normal nutrients that would include grain/starch/sugar.

I do not believe that we were meant eat very high fat just because we have to add, artificially increasing it.

But the bottom line is that those who follow the JUDDD rotation seem to reap the benefits that SIRT1 provides.
The markers studied in the Horizon special certainly show that.

Many of us are getting older and still healing through JUDDD.
So when do we start losing the ability?
I'll be 61 so not old, old age but certainly getting there.
And I think we have some 70 ish JUDDD'ers, right? If I get to that age eating this way and remain active, I'll be thrilled.

BUT, I do not want to be on this planet w poor quality.

I dumped all my supplements except D3, C, mineral salt combo.
My NP would like for me to take a multi but they repeat so.......That's it!!
I do not believe that supplements make up for nutrients missed via diet.
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Old 09-09-2012, 09:06 PM   #25
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I tend to eat quite a bit of fat, although it is mostly from walnuts, mac nuts and avocados. Very rarely eat cheese or dairy fat. I also love fat from salmon & turkey. I just recently decided to lower my protein and raise my carbs and fat. Don't know if it is going to affect my losses, but will report back.

I posted quite a few links to the benefits of Sirt-1 on the brain. I certainly hope my brain is getting a boost, because I definitely need it for the work I do.
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