Reducing Protein in Diet Improves Health and Extends Lifespan

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According to new research findings, reducing the amount of protein in the diet produces an array of favorable health outcomes, including an extension of lifespan, and these effects depend on a liver-derived metabolic hormone called Fibroblast Growth Factor 21.

A Single Hormone Directs Body’s Responses to Low-Protein Diet.

Mice live longer and lose weight while eating more when the hormone FGF21 is present.

A single hormone appears to be responsible for the lifespan extension produced by a low-protein diet.

A new study from Pennington Biomedical Research Center, published recently in the journal Nature Communications, found that reducing the amount of protein in the diet produced an array of favorable health outcomes, including an extension of lifespan, and that these effects depend on a liver-derived metabolic hormone called Fibroblast Growth Factor 21 (FGF21).

It has long been recognized that reducing the amount you eat improves health and extends lifespan, and there has been increasing interest in the possibility that reducing protein or amino acid intake contributes to this beneficial effect. Several recent studies indicate that diets that are low in protein, but not so low that they produce malnutrition, can improve health. Conversely, overconsumption of high-protein diets has been linked to increased mortality in certain age groups.

A few years ago, Pennington Biomedical’s Neurosignaling Laboratory discovered that the metabolic hormone FGF21 was a key signal linking the body to the brain during protein restriction. Without this signal, young mice failed to change their feeding behavior or metabolism when placed on a low-protein diet.

“Our data suggest that FGF21 talks to the brain, and that without this signal the mouse doesn’t ‘know’ that it is eating a low-protein diet. As a result, the mouse fails to adaptively change its metabolism or feeding behavior,” said Christopher Morrison, Ph.D., Professor and Director of the Neurosignaling Lab.

Christopher Morrison and Cristal Hill

Christopher Morrison, Ph.D. and Cristal M. Hill, Ph.D.

The group’s newest work, led by postdoctoral researcher Cristal M. Hill, Ph.D., demonstrates that low-protein diets produce beneficial metabolic effects in aged mice, improving metabolic health, reducing frailty, and extending lifespan. These beneficial effects were also apparent when protein intake was reduced in middle-aged mice, even protecting against the detriments of obesity. Importantly, these beneficial effects were lost in mice that lacked FGF21, suggesting that its action in the brain is critical for the increase in health and lifespan.

“We previously showed that FGF21 acts in the brain to improve metabolic health in young mice fed a low-protein diet. These new data extend this work by demonstrating that FGF21 also improves metabolic health and extends lifespan. Collectively, these data provide clear evidence that FGF21 is the first known hormone that coordinates feeding behavior and metabolic health to improve lifespan during protein restriction,” Dr. Hill said.

However, Dr. Hill said several questions remain. It’s unclear exactly how these observations will translate to aging humans, but the hope is that this work will uncover novel molecular and neural pathways that can be leveraged to improve health in people.

“This groundbreaking research has important implications for extending the health and lifespan of people. If scientists can better understand how diets and nutritional hormones like FGF21 act to extend lifespan, these discoveries could offset many of the health issues that occur in middle age and later,” said Pennington Biomedical Executive Director John Kirwan, Ph.D.

Reference: “FGF21 is required for protein restriction to extend lifespan and improve metabolic health in male mice” by Cristal M. Hill, Diana C. Albarado, Lucia G. Coco, Redin A. Spann, Md Shahjalal Khan, Emily Qualls-Creekmore, David H. Burk, Susan J. Burke, J. Jason Collier, Sangho Yu, David H. McDougal, Hans-Rudolf Berthoud, Heike Münzberg, Andrzej Bartke and Christopher D. Morrison, 7 April 2022, Nature Communications.
DOI: 10.1038/s41467-022-29499-8

This work was supported by the National Institutes of Health grants R01DK105032, R01DK121370, R01DK123083, and F32DK115137. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

17 Comments on "Reducing Protein in Diet Improves Health and Extends Lifespan"

  1. This seems almost too silly to comment seriously on.

  2. Again with the mice research. This website should change its name to Mice
    Because it happens in a mouse does not mean it will happen in a human. In fact it rarely ever transfers from house to human psychology, so the research is a complete waste of time and money.

  3. Headline: “Reducing Protein in Diet Improves Health and Extends Lifespan”

    Summary: “However, Dr. Hill said […] It’s unclear exactly how these observations will translate to aging humans…”

    People eat too well. Simple as that. Consume whatever your body is used to, but just a whole lot less. Any mouse will tell you ….

  4. So just not eating meat produces fibroblast? Is it a state,produced by a vegetable? This article is way too vague

    Suppose in moderation, most food ok.But this is giving me an eating disorder. WTF

  6. The exact opposite of these results were concluded by a Harvard medical study that was released two weeks ago. I will try to find the link and post.

  7. E Anubis Plurum | May 18, 2022 at 9:56 am | Reply

    What a horrible title, picture of foods most doctors tell you to eat and the article in general – it doesn’t specify a damn thing any one of us can identify with!


  8. They need to clarify what kind of protein. Animal protein is harder on the liver and kidneys.

  9. And yet another study has shown eating less calories and eating at the right time extend your longevity.

  10. Charles G. Shaver | May 19, 2022 at 8:17 am | Reply

    I don’t know about mice and NGF21 but I do know that in humans protein is what triggers a food allergy immune response. What is less obvious and a potential problem for vegans is that animal protein may contain more essential nutrients than an equivalent amount of plant protein, and/or be more digestible. Surely, reducing food allergy reactions can help to extend one’s life.

  11. You have got to be kidding me

  12. Then why do people in Hong Kong who are the biggest meat eaters, eating an average of 1.5 pounds per day, the longest living people on the planet?

  13. If studies are done on humans, I think demographics such as blood type (which has prompted entire books on blood type and nutritional needs especially protein intake) and heart health, lack of obesity, exercise regime, income level, and type of protein eaten should be considered (for example – is it fatty or lean meat people are eating? Does it have iron?). I’m a type O and I am not a good candidate for a vegetarian or low protein diet as compared to other blood types. I understand you were referring to a level where it isn’t malnurishing, but I was eating a bunch of lentil pasta and protein bars and my feet were still swelling for the first time in my life (in my 30s) when I was avoiding meat and eggs (pretty sure it was protein deficiency, I’m thin, my feet had never swollen in my life up until that point and it completely went away after I started eating meat and eggs again.) I also was bruising a lot more easily due to low levels of B vitamins I believe. I’m normally in excellent physical health and an excellent BMI and nothing had changed but my protein intake. That was the most unhealthy I remember feeling was when I cut out meat and eggs as a type O blood type. I think quality of life and lifespan are different. Ideally it would be nice to have both. I think my brain works better when I get meat and eggs also as a type O. If you do experimental human groups please consider asking about swollen feet and bruising and other signs of malnutrition. I think unless helped, people can’t identify signs of protein deficiency as connected to their diet, especially in those with blood type O.

    • Sorry Sarah but blood type doesn’t have anything to do with diet. Many authors will say anything to sell books. I feel like you’ll never be healthy if you go on the way your going Just go Whole-food Plant-based and do research on how to do it right and forget about the rest.

  14. William G Stewart | May 20, 2022 at 12:36 pm | Reply

    I went vegan a year ago, and I eat about half as much protein as I used to as a result. And I can say WOW I feel way better! Study seems obvious to me now. I train in junior gymnastics and noticed a that my healing and recovery time from workouts reduced as well. It’s so profound going Plant-based that everyone that seriously tried it would agree. It’s the diet of the future for sure.

  15. SteveMatthew | May 21, 2022 at 1:15 am | Reply

    This is a healthy approach to shed pounds. This works great with vegetarian protein powder.

  16. The article does not address what type of protein was used on the mice. All proteins are different. They have different absorption rates and blood plasma longevity.

    Protein is the building blocks of life. Two substances only can produce mitochondrial DNA and that’s protein and fat, not carbohydrates.

    Protein can do whatever fat and carbohydrates do but the latter two can not do what protein does i.e. brain fuel, body fuel, prevents muscle atrophy, build’s muscle, promotes higher GH levels, instant btu’s and energy, , promotes a lean body, easy digestion compared to fats and carbs, promotes higher metabolic rate, prevents mucke atrophy and cannabilism, never hungry, etc…

    I myself consume between 160 to 240 grams of protein per day with a #155 body weight. It’s all measured by hourly consumption and is adjusted to my bodies demand. My body stops functioning properly if not given a half gram of protein per every pound of body weight divided over a 24 hour period.

    Excess protein not used or causing spikes is bad which causes protein urea or flushing via cell walls.

    When my diet changes so does my metabolism. My body does not like carbs at all which promotes metabolic disease when intake is excess. I’m sluggish, low energy, brain fog occurs, muscle growth and maintenance is greatly reduced and my growth hormone levels vastly decrease. I’m 52 and still look 30 years younger then everyone my age and can only thank my high protein diet used since age 15.

    So maybe the study could have been improved. Nice do not give feedback like humans which should have been used since the study will be used for human reference.

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