Tuesday, April 20, 2021

Maintaining muscle function in to old age

An aside: Public Service announcement. I seem to have a lot of Faceache/book friend requests coming through at the moment. Once upon a time I accepted all friend request and have read some interesting posts as a result. But I don't use Faceache for anything technical. The occasional orchid picture or flat water paddling snap is about it. So now I don't accept friend requests unless I know the person. There's nothing Hyperlipid-ish in my FB posts and the algorisms bury the social stuff I'd like to see if I have too many friends. Sorry if it seems rude, it's not meant to be but there is no way round it. End of Public Service announcement.

Back to the post:

The start of the current gross stupidity of lockdown-2 seems to have vanished in to the haze of the past. I can't remember when I last went bouldering, pre-idiocity. I guess it was some time last December. In the dim and distant past of lockdown-1 the climbing wall was completely reset but during the current period of enforced sarcopaenia only small areas were changed, so I got the chance to see how well I fared on some familiar routes after months of enforced idleness.

Pretty well. Endurance was a bit down and finger strength was laughable but on routes with big chunky handholds going up the main competition wall my bulk muscle seems to cope remarkably well.

On which subject I was interested in this paper put up on Faceache by Jay Wortman

The ketogenic diet preserves skeletal muscle with aging in mice

which is strong in it bias-confirming ability, bearing in mind that the keto mice were not exactly spending hours a day in the gym. It's the same group that produced this study

which is also exactly what you want to hear if you are an old bloke like me with young kids.

But I never blogged about the original paper. It has a certain flaw, common to both papers, which made me slightly cautious. The paper is best described as one of those "think about it" studies. Here are the diets used for both:

and here are the survival curves

The first problem is that there is no mention of gas chromatography. We have no idea of what the PUFA content of the lard was and the lard makes up something over 80% of the calories of the ketogenic diet.

In a deeply ketogenic diet such as F3666 it doesn't matter what the PUFA content is and the lard content is relatively low anyway. But for a rodent diet supplying 10%of calories as protein and maybe 20-25% of calories as PUFA it might matter. It mattered in these papers:

"During this one month [ie the lead-in at 12 months of age] period, food intake was measured to determine the daily food intake required by these animals. At 12 months of age, mice were randomly placed on one of three diets: control, low-carbohydrate diet (LCD), or ketogenic diet (KD). The control diet contained (% of total kcal) 18% protein, 65% carbohydrate, and 17% fat. The LCD contained 20% protein, 10% carbohydrate, and 70% fat. The KD contained 10% protein, <1% carbohydrate, and 89% fat. For the longevity study, food intake was set at 11.9 kcal/day, and decreased to 11.2 kcal/day after weight gain was observed during the first weeks of the study."

The studies combined a ketogenic diet with calorie restriction. Calorie restriction is a known longevity promoter. Duh. And keto didn't maintain a normal weight.

Lard can contain anything from almost no PUFA up to more than 30% PUFA, depending on what the pig was fed on and how adulterated the lard has been with cheap vegetable oils.

So these ketogenic mice had to be on a calorie restricted diet because otherwise they gained weight. They were on a diet containing around 20%-ish of calories from linoleic acid. If they felt a hypo in the middle of the light period they would have eaten to correct the hypo. Pathological insulin sensitivity. Or just the loss of calories in to adipocytes without a hypo would generate simple hunger to off set those calories lost in to fat calls, ie weight gain.

Of course it's just a rodent study and maybe people would be different.

Or, more likely, maybe not.

As a more general point it's also worth noting that the improvement is in the median lifespan, not peak longevity. The first mouse to die was in the keto group, the last in the low carb group. Median does not mean an intervention is invariably perfect for all individuals.

But it's as good as we have at the moment.



Christopher Kelly said...

Hi Peter! My colleague Megan N. Roberts is the first author on the second paper you cited. I was wondering, could I persuade you to join her as a guest on the Nourish Balance Thrive podcast? I'd like to hear you both talk about protons and obesity :)

Peter said...

Hi Christopher, that would be excellent! Best contact me via email, it's on the upper left side of my Blogger profile.


Justin said...

Man, I was just getting ready to send you a friend request. Lol!!!! ;)

karl said...

This type of paper, once again, has multiple and poorly defined variables. Imagine instead, if they had used a chemically defined diet with only one variable. The new generation needs a new Richard Feynman.

I think muscle mass is quite important for insulin sensitivity. They closed the place I would run in the winter due to the CoVid hysteria, I couldn't always run outside due to ice etc.. I also find I have strolled less, just so depressing and isolating seeing people with masks - in and out of doors. I too have lost some endurance.

My life improved when I quite FB - and after that lesson, I knew better than to ever use twatter. Quite literally, YOU the user is what they sell (I think the collected information is over valued - but they collect every key stroke - posted or not - pass it through Bayesian filters and sell to the highest bidder. Does the average user know they are collecting keystrokes - mouse position - pauses over icons?).

I've thought more about the crazy-time we are in - even before CoVid people were more isolated due to substituting social media for real life socializing. Talking to people in public ends up with us rubbing up against people that may disagree and not share our same views. This is a good thing - helps people test reality. Post CoVid we have masks which hide a bunch of the 46 facial muscles that express emotion. Add to that the canceling communication that varies from the official line and we have a huge paradigm shift.

Tolerance of different opinion is evaporating - some businesses use systems to avoid group-think because they know that it prevents people from showing a full range of options. It is a hall-mark of totalitarianism to prevent dissenting points of view.

The internet provides the opportunity to only see/watch people with the same opinion - what in electronics we would call positive-feedback - and it results in a signal that goes to one extreme or the other. With out negative feedback, there is no analog signal - just extremes - polarized output.

Testing of reality is quite important. I know there are a number of people who's on-line persona is fiction - play acting - and seems to be associated with hypersensitivity - no tolerance of other points of view or anything that might disrupt their fantacy. Teasing, is in part, pushing an alternative interpretation of one's actions - not evil.

I think we all share a common reality - it is not always easy to discover - the scientific method - epistemology take discipline and hard work.

I remember being taught that psychosis is different than neurosis - because of the break with reality. Where is humanity headed?

Tucker Goodrich said...

"For the longevity study, food intake was set at 11.9 kcal/day, and decreased to 11.2 kcal/day after weight gain was observed during the first weeks of the study."

Nice catch there. Skimmed these the other day but am working on something else, so didn't drill down.

Yes, would be interesting to see a longevity curve of fat ketogenic mice...

HR Enduro said...

Do you have any thoughts on time restricted eating Peter? Do you follow any such protocol? I have just finished reading this article and the improvement on biomarkers for patients and mice in these studies is interesting, https://www.foundmyfitness.com/topics/time-restricted-eating

kind regards,


Peter said...

Justin, sorry, that's how it goes!

karl, I have to agree the masks is what gets me down a little. There was a time when they simply symbolised gullibility. Now they are a symbol of unquestioning obedience to morons.

Tucker, I'd love to see the same study substituting beef dripping for lard, with no soy oil. Could be a winner. Jim Johnson's lab work with Surwit fed, fat, non-ketogenic mice showed they do really well for median lifespan. Keeping their inner mitochondrial membranes relatively PUFA free and MCTs, especially caprylate, convert to palmitic acid in vivo... Sounds fine to me.

Hi HR Enduro, not deliberately. I find I work and climb best fasted. So some days breakfast will be at 3pm, but otherwise not... I work two mornings a week and climb once a week on a good week.


Passthecream said...


Moving from the sublime to the ridiculous. Very sophisticated technology however ???Palmitate is used in their heart prep but there is no breakdown of the contents of the feed. Zilch. To cap it off they add intralipid to their mitochondrial prep ...

Passthecream said...

Mea culpa. It's oil! Octane rating not specified.

"half the rats were switched from standard chow to a custom-produced high fat diet (Special Diet Services, Witham, Essex, UK), which had an AFE of 5.1 kcal/g, comprising 55% from oil,"

Results as expected.

Peter said...

Haha Pass, they've clearly not read the literature on low dose 2,4-DNP!

And fructose, the need is to get right down to basics. Does it have anything to do with insulin, the ETC and why does it release free fatty acids from adipocytes? Very, very complex...


karl said...

Re fructose - I think a diet high in fructose isn't good for people - ends up down the same metabolic pathway as ethanol - which ends up stressing the liver. So the question is at how many grams/day of ethanol does the damage begin? - which could be converted to fructose.

The other narrative I have heard is it is more reactive than glucose - forming AGE 10x - but I couldn't find the research this claim is based on. The liver seems to think it is important to get rid of fructose ASAP..

Lustig claims it causes T2D - not sure how he imagines the low level mechanics.


I remember a study showing people ate more if they had a fructose containing drink - could be effecting appetite via the liver response? Could be the tryglys blind the brain from the effect of leptin? https://diabetes.diabetesjournals.org/content/53/5/1253.long

We do know from chemically defined diet work that fructose spikes trygly - Milton Winitz papers from back in the 1960's..

Shouldn't have been a surprise - Harold Higgens back in 1916 said fructose more easily converted to fats (can't find the original reference - or why he thought that).

The problem is at these system levels, everything effects everything - with non linear nested rats nest of feedback loops - one can grab what ever bit of some loop and start a narrative.

If someone can't resist the carbs - might be a good idea to get carbs without the fructose.

Most starch is just glucose - but a chemically defined diet study where they switch out glucose/fructose/galactose/lactose/ etc.. probably could help find the unexpected bits. (not sure the research industry actually wants to find anything unexpected..)

T2D will kill a lot more people than CoVid - you would think systematic targeted research would be important..

Peter said...

karl, "The problem is at these system levels, everything effects everything" absolutely. This is my drive to get to the most basic signalling level. Above that 4 billion years can weave quite a cat's cradle! How boring would it be if it was all cytoplasmic signalling.


Passthecream said...

Karl, this is a paper Peter linked recently. It gives a convincing overview of fructose wrt human evolution


It's hardly surprising that fructose has deep hooks into our metabolism if we are descended from fructivores. The authors are a part of a group working on ways of countering fructose metabolism. (Why bother to change your lifestyle when there might be a drug for it?)

The lead author has done some interesting work: https://pubmed.ncbi.nlm.nih.gov/?term=Johnson+RJ&cauthor_id=31621967
Including 'Uric acid-dependent inhibition of AMP kinase induces hepatic glucose production in diabetes and starvation: evolutionary implications of the uricase loss in hominids'


"These studies identify a key role AMPD and uric acid in mediating hepatic gluconeogenesis in the diabetic state, via a mechanism involving AMPK down-regulation and overexpression of PEPCK and G6Pc. The uricase mutation in the Miocene likely provided a survival advantage to help maintain glucose levels under conditions of near starvation, but today likely has a role in the pathogenesis of diabetes. "

Passthecream said...

BTW Peter the link to the myocyte paper in the previous post has gone weird.

Passthecream said...

.. myotubule ...

karl said...

@ Pass -
A bit skeptical on the Fructose metabolism as a common evolutionary pathway of survival associated with climate change, food shortage and droughts - paper.

I think fructose is important in terms of endogenously production -- polyol pathway but I don't think it was a major source of food other than specialty species. If you look at modern food sources, most calories just don't come from fructose. More like an occasional treat of calories. But why did some fruits learn to produce fructose?


Did these folks get the arrow of causation right?
High salt intake causes leptin resistance and obesity in mice by stimulating endogenous fructose production and metabolism
Did the high salt cause T2D or did the high carbs cause retention of sodium?

This paper Endogenous fructose production and metabolism in the liver contributes to the development of metabolic syndrome begs questions about dietary fructose.

I think too much fructose is a bad thing - did earlier life really live on it - Not sure that there is a 'good minimum amount to eat'? Or was there once a reason to convert glucose to fructose that is lost now?

Strange detail - seamen has a bit of fructose - appears important for sperm. How did that evolve!? Legacy or earlier life used it or for some other purpose?

There are bits about fructose being anti-bacterial.
- could this explain above?

Uric acid and polyol pathway activation in fatty liver

Endogenous fructose production and metabolism in the liver contributes to the development of metabolic syndrome

Here is a riddle:
Fructose Production and Metabolism in the Kidney
They ask "Why humans have such a deleterious mechanism to produce fructose is unknown, but it may relate to an evolutionary benefit in the past."

Seems like we might learn something if we can figure out the 'why'.

I think we can't ignore Lustig. I think there are a lot of people who would have better lives if they consumed less fructose containing sugars.

So what if BOTH things matter - fructose containing sugars got cheap - people started eating large amounts of concentrated PUFA (both happened about the same time) - and now we have a seriously sickly population - not just in the US - even the third world is getting hurt.

The various idiopathic syndromes - CF/Fibror etc - could be related to fructose consumption

But I am still thinking that some of these syndromes are actually from life times of viral exposure - dormant/dead viruses that have mucked up Mitochondria - Perhaps particularly in nerves..

Passthecream said...

Karl "I don't think it was a major source of food other than specialty species"

Seems to be the case that we are ultimately descended from just such a species. The loss of the relevant food sources due to the Miocene catastrophe kicked off the processes which led to where we are currently.

Whether or not that is the case, there's no no doubt that now, massive amounts of sugar together with seed oils in the food chain are giving rise to another evolutionary bottleneck via the diseases of civilisation. Any rise in viral infections is probably secondary to the increase in human population density which is in turn due to the Neolithic 'revolution'.

altavista said...

If you're in the last 50% to go, it's pretty unimpressive. Better go for the pizza when young. Hopefully the difference was in quality of life. But for the worst 25% of genes, LC looks worthy.

Passthecream said...


Judith Johnson said...

Peter-are you still following the Paleolithic Ketogenic diet? Just wondering how that is working out. Thanks

Peter said...

Hi Judith, no, I've introduced a small amount of dairy. Coffee has come and gone and come and gone again. I have a small portion of root vegetables once a week but this doesn't take me out of ketosis. I currently mostly eat high fat beef (20% fat by weight) with some extra beef dripping but the ratio will not hit the PKD 2:1 value.

If I had a specific medical issue (that I was aware of!) I would have no trouble in tightening right down but logistically the lapsed version is very easy compared to the therapeutic correct PKD. But I wouldn't call it that.


altavista said...

Whats the fattiest cut? Bolar blade?