In going through and catching up on all the online issues of Science, I finally reached the most current issue, which contains an article of interest. Originally published in 1970 in the journal Nature, this article was featured in the current issue of Sage KE, an anti-aging supplement to Science, as a blast from the past in their Classic Papers section.

The paper was the first to show that the accumulation of non-functional, or junk, proteins play a role in the aging process. This article caught my eye because of another on ketosis I had read recently and had touched upon in a previous post.
ketosis cleans lysosomes
Anti-aging scientists are now pretty sure that one of the forces behind the aging and senescence process is the junk protein matter that accumulates in the cells, hampering cellular function. If the junk builds up enough, it basically crowds out the working part of the cell, killing the cell off in the process.

As this inexorable process proceeds, more and more cells function less and less well until we, as a being, cease to function. There are other processes driving the aging function besides this accumulation of cellular debris, but if we can make some headway with cleaning out the junk, then we should be able to make the cells, and by extension us, function better for longer.

We have little chemically-operated waste disposal systems in our cells called lysosomes. Cellular debris that gets hauled to the lysosomes and dumped in gets degraded into individual amino acids, which are released into the circulation and used to re-synthesize other, functional, proteins.

The process of transporting the junk proteins to the lysosomes is handled by enzymes designed for that purpose found within the cells. As long as the enzymes are working up to snuff, the junk doesn’t accumulate. But as the Nature paper shows, the aging process takes its toll.

Random errors in protein synthesis of these enzymes due to the aging process means that some end up being functional while others aren’t. The non-functional enzymes then not only don’t help haul the junk to the lysosomes, they themselves become junk. It’s easy to see what’s going to happen as time marches on.

But how can we slow this process and de-junk our cells?

Stay in ketoses a lot of the time. How do we stay in ketosis? By following a low-carbohydrate/ketogenic diet.

How does ketosis help us de-junk our cells?

A paper appeared in the Journal of Biological Chemistry last year that tells the story.

Ketones stimulate the process of chaperone-mediated autophagy (CMA). What is CMA?

It is

a cellular process that allows cells to remove proteins, organelles, and foreign bodies from the cytosol [the watery interior of the cell] and deliver them to the lysosomes for degradation.

Why would the body be designed for ketones to stimulate CMA?


Ketosis is one of the signs of long term starvation. Ketones are produced throughout the day and are perfectly normal, but sustained ketosis takes place during starvation and sends a message that the body needs to conserve both glucose and protein.

The body begins to conserve glucose by signaling to many of the organs and tissues to start using ketones for energy instead of glucose. The body conserves protein by decreasing its use of glucose because in the absence of dietary carbohydrate (as in starvation) the body makes glucose out of protein.

Conserving glucose by switching to ketones allows the body to preserve its protein stores. The other thing the body can do is to make sure that the protein it does break down to use for glucose formation comes from non-essential sources. What more non-essential source can we have than useless junk proteins floating around inside the cells?

The ketones themselves stimulate the process of CMA to salvage all the junk protein to be used for glucose conversion.

Ain’t nature great?

Now, all we have to do to slow the aging process is to stay in some degree of ketosis most of the time and let nature take her course and clean all the junk out of our cellular attics. How do we do that? Easy. Keep our carbohydrate intake at (or preferably below) 100 grams or so per day.

Why that particular number?

Let’s figure.

It takes about 200 grams of carbohydrate per day to provide glucose for all the structures in the body that require it. After a period of low-carbohydrate intake or starvation that amount required drops to about 130 grams per day because about 70 grams are replaced by ketones.

We never really get below that because certain cells can’t convert totally to ketone use and continue to require some glucose. For instance, the red blood cells must use glucose for energy as do some cells in the kidneys and the brain and central nervous system.

But not to worry, the liver can easily make 200 plus grams of sugar per day to ensure that these tissues get all they need. But the liver makes most of this glucose via a process called gluconeogenesis (the generation of ‘new’ glucose) out of protein.

So, if we decrease our carbohydrate intake to below, say, 50 grams per day, the amount advised in Protein Power and other enlightened books on carb restriction, we’re in a deficit to the tune of about 150 grams per day. No problema. The liver makes up the deficit out of protein.

As we start making ketones to replace the glucose, the deficit drops to about 80 grams per day, which the liver can easily provide. But here is the neat part. Most of the glucose the liver makes won’t really come from protein from our tissues; it will come from the protein we eat. We’re not starving; we’re eating a high-protein diet. So we have plenty of protein to make glucose as we need it without robbing our muscles and other protein tissues that would get pillaged were we really starving.

But, deep in the bowels of our cells this fact is unknown. All the cells know is that ketones are all over the place, which is the signal to start the CMA process to break up junk protein.

We end up losing body fat, which is both burned for energy and converted to ketones to replace glucose, while at the same time we maintain our needed protein structures because we’re eating protein, and we de-gunk our cells. All while eating steak and eggs and lamb chops and ham and…

It just one more reason the low-carb diet rules.


  1. This is an interesting theory. The Inuits, on their traditional diet must have stayed in ketosis for the major part of their lives. I wonder if that translated in longer healthier lives for them? (those who survived to old age).

  2. The question one needs to ask is did staying in ketosis most of their lives lead the Inuit to live longer lives than they would have in the conditions under which they lived? Remember, in primitive societies the biggest impediments to longevity were trauma and infectious diseases. As societies became Westernized trauma and infections were replaced by diabetes, heart disease, cancer, and all the rest of the disorders of the ‘civilized’ world.

  3. It was possibly just a subjective impression, and even if true, may be due to factors other than diet, but Steffanson seemed to think the Inuit, in spite of being healthy, aged more quickly than Americans of his time:
    “The danger is that you may reason from this good health to a great longevity. But meat eaters do not appear to live long. So far as we can tell, the Eskimos, before the white men upset their physiological as well as their economic balance, lived on the average at least ten years less than we. Now their lives average still shorter; but that is partly from communicated diseases.
    It has been said in a previous article that I found the exclusive meat diet in New York to be stimulating – I felt energetic and optimistic both winter and summer. Perhaps it may be considered that meat is, overall, a stimulating diet, in the sense that metabolic processes are speeded up. You are then living at a faster rate, which means you would grow up rapidly and get old soon. This is perhaps confirmed by that early maturing of Eskimo women which I have heretofore supposed to be mainly due to their almost complete protection from chill – they live in warm dwellings and dress warmly so that the body is seldom under stress to maintain by physiological processes a temperature balance. It may be that meat as a speeder-up of metabolism explains in part both that Eskimo women are sometimes grandmothers before the age of twenty-three, and that they usually seem as old at sixty as our women do at eighty.”

  4. I’m curious as to where this quote from Stefansson came from. A lot in it seems strange. For example, for one to become a grandmother at 23 would mean being impregnated at age 10, having a daughter at age 11, who was herself impregnated at age 11 and having a child at age 12. This is all highly improbable given that women in primitive societies reach menarche at much greater ages than women in modern times. It has been estimated that women in most primitive societies didn’t reach menarche sometimes until in their late teens. This fact alone makes the idea of one lady being a grandmother at 23 fairly preposterous, much less it’s being a somewhat common finding.
    As far as I know there is no proof that meat is a “speeder” of metabolism just as it is absurd to think that people mature early by avoiding exposure to chill.
    Stefansson was a pretty bright, observant guy, and I would be deeply suspicious of this quote unless I positively knew it came from him. If it did come from him, I would say he was a little off the mark the day be wrote it.

  5. I had a hard time finding any information about the actual life expectency of the Inuit of old, before the exposure to the West/Europeans and the diseases they brought. It’s too bad that the history of the Inuit was not recorded before this introduction. Inuit populations of today are not following their traditional diet, and have been “incorporated” into the Canadian/Icelandic/Russian government government programs. All this has led to a decreased life expectancy (my opinion). Alcholism, diabetes, heart disease, and suicide are all taking their toll on the Inuit. There are some elders that still subsist on large quantities of fish and game that have remained healthier than their offspring (that eat a more urbanized, civilized diet). But the culture and lifestyle of the Inuit of old has been lost for the most part.
    That being said, I suspect that the Inuit of old (more than 1,000 years ago) had far better health and greater life expectancy than the Inuit of today, solely because of their being a hunting culture. It is fascinating how every single part of their hunt was used. The fur, hide, muscle, stomach, bones, intestines, feet, fins – everything.

  6. Right now in Sweden a TV-series about the Inuit is being sent. It’s called “The Inuit Experiment” lead by Physiology Prof. Bengt Saltin, Muscle Research Centre University of Copenhagen. 16 Danish subjects are staying 42 days in Greenland together with the 8 Inuits. Physiology tests were made on the Danish group and the Inuit group, prior to the experiment. One difference found was that the Danish burned fat mainly in their thigh muscles, whereas the Inuit had effective fatburning in both legs and arm muscles.
    The Danish group was divided into two groups. Their task is to pull 80 kg loads for 8 hours a day. Next week comes part 2. So if there is an interest I can continue to report from Sweden! =)

  7. Google contains some information on where the quote might have come from:
    My opinion is that native people in general seem to age faster… even American Indians who don’t eat all meat. This could be due to hard living or any number of factors, including genetics. I believe that the only massively vegan society on earth is India and I wouldn’t say they are unusually young looking.

  8. A few things. The description of where minimum carbohydrate requirements are derived from was the first actual description of how they are derived. The only other one I’ve come across was from Dr. Lutz in his book, ?Life Without Bread?, who as I understand it found that 72 grams of Carbs per day was the most Type 1 Diabetics could tolerate without insulin. Maybe this discussion of minimum carb needs could find its way into a future Protein Power book.
    In re: Ketosis as a cell cleaner, more study is needed to determine its limits, i.e can it eliminate all the excess protein. Does enough ketosis occur in even lower carb diets to purge the cells of waste protein etc. This appears to tie into your 9/9/05 BLOG
    “Build muscle while you de-junk your cells”
    as one of the sources of the negative nitrogen balance.
    The discussion of Vilhjalmur Stefansson and the Inuit is also of interest. The quote apparently comes from an article in Harpers Monthly Magazine November 1935 also appears on the following website; with comments
    This website has some interesting comments on Mr. Stefansson?s observations. However, even if we take his observations that the Inuit are living at a faster rate as true, that does not necessarily mean it is a bad thing. My view point is that low carbing is not so much about life extension as quality of life extension.It is better to live, for example 60 healthy productive years than 70 years with increasing deterioration in particularly the last 10 years to the point that one is practically a vegetable in their last few years. Hopefully we are getting both, a relatively minimal life extension with a great improvement in quality of life.
    One final point is that the Inuit are not the only meat eating culture. The Masai of South Africa are also often cited as another example. It would be interesting to see how their lifespan compare to nearby tribes.

  9. Lost comment
    Excellent post, Mike! Very informative. I do have one comment about the use of the term, “starvation.” As you point out, there are two processes involved, both referred to as starvation, gluconeogenesis from dietary and non-essential proteins, and the breakdown of muscle tissue for that purpose. Only the breakdown of muscle tissue is actual starvation. We should use another term to refer to what is, as you point out, a normal and beneficial process. Again, why refer to lowered carbohydrate intake as starvation when what we”re really doing is getting our carbohydrates to a level that will allow more beneficial processes to take over.
    See, it’s not just attacks on the left that get me to comment!

  10. Yes, there is interest in the report from Sweden, at least on my part. Please keep us updated. Thanks.

  11. Good point, Chuck. And I am glad to see you commenting on a non-political blog.
    I agree that there should be a better term, so let’s invent one. The medical literature refers to the metabolism under discussion as the ‘starvation response.’ It’s also called the post-absorptive state, but that’s not really accurate either because the post-absorptive state means the period of time ‘after’ digestion has taken place, and, as you point out, these metabolic changes are in place most of the time, not just during the ‘post-absorptive’ state. I’ve seen it referred to as the ‘fasting’ response also, which, though accurate in a sense, isn’t really accurate because one doesn’t fast on a low-carb diet. The whole idea shows that, at least in the minds of the metabolic scientists of the last century or so, the high-carbohydrate diet and its metabolic consequences are considered the ‘normal’ state, whereas the perfectly normal metabolic responses to a low-carbohydrate diet are tagged as somehow being abnormal.

  12. Just saw this one. Sounds a little misguided to me:
    Atkins Diet Linked to Life Threatening Complication
    Thursday, March 16, 2006
    LONDON � The popular Atkins diet could be linked to a life-threatening complication which one woman who claimed to be following it developed, according to doctors who published a case report on it Friday in a British medical journal.
    The Atkins diet calls for restricting carbohydrates to achieve weight loss, then gradually adding them back in. However, many people who say they’re following the diet actually eat large amounts of protein and fat.
    Doctors from New York University wrote in The Lancet journal of a 40-year-old woman who developed a dangerous condition called ketoacidosis, a dangerous buildup of acids called ketones in the blood which can lead to patients falling into a coma.
    However some outside experts said the case is rare and does not reflect a major health threat associated with low-carb diets.
    “I think this is an isolated case. The idea that serious ketoacidosis could be triggered by a low-carb diet does not happen very often,” said Dr. Paul Clayton, president of the forum on food and nutrition at the Royal Society of Medicine in London.
    Atkins Nutritionals referred calls for comment to the Dr. Robert C. Atkins Foundation, a medical research charity run by Atkins’ widow, Veronica. No one at the foundation could immediately be reached for comment.
    The patient, who was not identified, was admitted to an intensive care unit for four days after becoming short of breath. Before being hospitalized, she had lost her appetite, felt nauseous and was vomiting four to six times a day, the doctors wrote in the paper.
    Tests confirmed ketoacidosis.
    Ketones are produced in the liver when insulin levels fall due to starvation or diabetes.
    “Our patient had an underlying ketosis caused by the Atkins diet … This problem may become more recognized because this diet is becoming increasingly popular worldwide,” said Professor Klaus-Dieter Lessnau, who led the team from the New York University School of Medicine.
    Clayton said that the main problem of high protein diets is in the strain they put on kidneys and the risk of renal failure.

  13. Just wanted to clarify that Type 1 diabetics cannot “tolerate” ANY carbohydrates without insulin, much less 72 grams (Approx. 5 slices of bread). Type 1 diabetics do not produce ANY significant level of insulin, and thus do not even make enough to stay alive (basal insulin) during complete fasting. That is why ALL Type 1 diabetics died before the availability of manufactured insulin, regardless of a “starvation diet” or not. With the proper corresponding injected insulin amount, carbohydrates are not harmful to Type 1 diabetics, as their proplem is that they have an insulin deficiency, NOT a carbohydrate metabolism problem.

  14. Barry Sears says in his books that ketosis is bad because continued ketosis within three to six months will cause fat to become “fat magnets” which are 10 times more active in their ability to accumulate fat. Do you agree? If so, is your position that you should alternate periods of being in and out of ketosis?
    I don’t agree. Ketosis is a perfectly normal condition that most people are into and out of throughout the day–even those on higher carb diets. Most tissues can use ketones as fuels; some tissues–heart muscle, for example–prefer them. The idea that prolonged ketosis converts the fat cells into ‘fat magnets’ sounds like something Jane Brody would write.

  15. Natures law says – in the unfavorable condition, developing and aging processes of ALL organisms speed up. They must hurry to give ‘seeds’ before they die. In the inuits case this condition could be a cold climate, in the Western societies – excessive consumption of carbs. In my ‘previous’ life, I’ve never heard of a menarche at 8 – 9 years of age. Every girl I knew got there when 12 – 16 yrs old.
    Another thing. Talking about life expectancy we should consider insulin, bypass surgeries, knee and hip replacements, all life stile medications and alike – the stuff that keeps so many people alive. Sorry, but I cannot help thinking of these folks as of walking and talking ghosts. These lives are due to the economical status of the society only.
    Probably an astute observation.

  16. Phenomenal explanation. I am in moderate ketosis per ketostix testing today and must say am excited about the potential results I am going to see and the life long path to better health. I appreciate the detailed simple explanation of what is going on in my body and how the process occurs to keep me looking BEYOUtiful!
    Tonya L. Woods

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