You sure hear a lot about bodybuilders who die young.

This was one of the big things I wanted to dig into when Rachel and I started researching the science behind human longevity.

I’ve always been a pretty skinny guy, and as I looked into what it would take for me to put on some muscle, I kept coming across internet rumors and vague warnings about how people who were too into building muscle were dying in their 50s and 60s (or sometimes earlier).

A lot of these guys were dying of heart attacks, cancers, and kidney failure, and many people blamed their poor health on, partly, eating way too much protein.

Protein was vilified as “as bad as smoking” and even directly linked to a bodybuilder’s sudden death at 25.

In the longevity community of spanners and others concerned with extending their lives, protein is also a concern because it switches on the mTORThe 'mammalian Target Of Rapamycin.' A complex in most cells that directs cell growth. and IGF-1Insulin-like growth factor 1, a growth hormone that helps build muscle. growth pathways in the body, and switches off the AMPK'Adenosine monophosphate-activated protein kinase.' An enzyme in cells that that inhibits mTOR and activates autophagy, or self eating, to clear out damaged parts of the cell. repair pathway. Following certain theories of aging, this could cause us to age faster as the body devotes more time and energy to grow than to repair the damage caused by aging. This paradox is often framed as “the growth-longevity tradeoff.”

So, does protein accelerate aging?

Research studies on the subject are all over the place. I’ll get into them below (as well as what I could find on the difference between plant and animal sources of protein, and what I plan to do with my protein intake after all my research), plus, an answer to the question of bodybuilder longevity!

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How might protein accelerate aging?

There’s some interesting science behind the idea that protein could speed up aging, and lots of people in the longevity space, including longevity experts like David Sinclair and Valter Longo, believe it might.

A lot of the evidence for this view comes from studies on protein restriction in animals. For instance, a low-protein diet extends lifespan in fruit flies, in mice (though notably not as much for female mice), and in yeast.

Additionally, studies that restricted several specific essential amino acids, the key building blocks of protein, also showed life extension and health-promoting effects in animals. Specifically, restricting methionine in mice and in yeast, leucine in mice, and tryptophan in rats either increased lifespan, improved metabolic health, or protected against diseases like cancer.

In humans, high intake of amino acids like methionineAn essential amino acid that helps with metabolism and blood vessel growth, but has also been tied to cancer growth and shorter lifespan. are also associated (in men) with greater risk for acute coronary events like heart attacks, and branch chain amino acid (BCAA) supplements have been proposed to play a role in athletes developing ALS (though, also, maybe BCAAs aren’t that bad as they seem to extend lifespan in mice?).

Protein restriction also appears to inhibit cancer growth in human cell cultures.

The other half of the evidence for protein accelerating aging comes from research into mTOR and IGF-1, the body’s growth signalling pathways.

When these two growth pathways are switched on, the body goes into growth mode, building lots of new, fresh cells. However, with these growth pathways turned on, the repair pathways (like AMPK) are turned off, so the body doesn’t spend energy shutting down damaged, senescent, or possibly malignant cells. If growth is always turned on, your body never repairs all the age-related damage that accumulates over time, and you age and get cancer and die faster.

And guess what turns on mTOR and “upregulates” IGF-1?

Yup. Protein (among other things).

Specifically, it seems certain of the amino acids in protein turn on mTOR as well as activate IGF-1.

High mTOR activation has been linked to a whole host of bad outcomes in both animals and humans including higher rates of cancer and obesity. Conversely, inhibiting mTOR seems to be a major way to increase lifespan in all kinds of organisms like roundworms and mice. In fact, inhibiting mTOR may be a key reason caloric restriction works to extend lifespan.

The same seems to be true with IGF-1, where high levels are associated with increased risks for cancer and faster cardiac aging. A big 2014 study found that lower protein intake correlated with lowered IGF-1, cancer, and overall mortality in people 65 and under (but interestingly had the opposite effect for those over 65, which we’ll discuss below). For those over 90 lower IGF-1 levels seem to predict greater survival as well.

That said, several studies and meta analyses have suggested IGF-1 levels that are both too high and too low increase all-cause mortality risk, so there may be more of a Goldilocks thing going on with IGF-1.

In fact (spoiler alert) there may be some evidence for a Goldilocks thing going on with protein as a whole, as well.

Let’s dive into the other, potentially healthier, side of protein and lifespan.

Can protein be good for longevity?

Remember all those bodybuilders dropping dead of heart attacks from too much protein at 27?

Turns out, if you go beyond the sensationalist headlines and dive into the numbers, it’s not actually that scary.

The Barbell looked at the men who competed in all of the Mr. Olympia and Arnold Classic bodybuilding competitions and found they had a lower death rate than the general population of American males (12.6% vs. 14.3%). This included nine born in the 1930s, of whom, they noted: “five are still alive; a sixth died at 85; only one—a suicide—failed to exceed the male life expectancy.” While bodybuilders do seem to die a little more frequently than other pro-athletes, most of the causes for this seem best explained by performance enhancing drug abuse rather than eating too much protein.

Maybe protein isn’t quite the villain it’s been painted as?

This shouldn’t be a total surprise; we need some protein just to stay alive, after all (they’re not called essential amino acids for nothing).

Plus, dietary protein is crucial for building and maintaining muscle, especially when paired with resistance exercise.

And muscle mass and strength has all sorts of health benefits, including protecting against age-related diseases like cancer, cardiovascular disease, and diabetes. Skeletal muscle mass is also, perhaps unsurprisingly, a predictor of longevity (being a frail 90-year-old is not ideal).

The flip side is also true: low muscle mass—especially sarcopenia in older people—is associated with a ton of bad health outcomes.

Sarcopenia predicts significantly higher mortality rates in older people, and also lowers survival rates and increases mortality for those with cancer. Protein supplementation (specifically whey plus resistance exercise) has been shown to help rebuild and maintain muscle in people afflicted with sarcopenia.

Other studies have shown a positive connection between protein intake and lifespan. For instance, a 2020 meta analysis of 31 different studies concluded, “Higher intake of total protein was associated with a lower risk of all cause mortality.”

Still more studies broke this down by age, with a 2019 mice study on dietary ratios finding, “Mortality in early and middle life was minimized at around one-part protein to two-parts carbohydrate, whereas in later life slightly greater than equal parts protein to carbohydrate reduced mortality.” The 2014 study in humans I mentioned in the previous section suggested high protein intake may increase mortality for people 65 and under, but actually decreases it for those above 65.

A 2019 review recommended a higher protein intake for older adults, noting:

“Several epidemiological studies have found a positive correlation between higher dietary protein intake and higher bone mass density; slower rate of bone loss; and muscle mass and strength. One epidemiological study showed a positive association between higher dietary protein intake and fewer health problems in older women.”

Still other studies have challenged the notion that eating less protein explains the life-extending effects of caloric restriction. A 2016 analysis suggested that, at least in rodents, “The effect of dietary restriction on lifespan in rodents is explained by calories alone,” and not by restricting protein intake.

In terms of gender differences, some research indicates women may even need more protein than is currently recommended. For instance, a study of elderly women found, “women with protein intakes greater than the midrange of 0.8–1.2 g/kg of body weight…tended to have fewer health problems over the next 10 y than those with protein intakes <0.8 g/kg.”

Another study of 80,000 women aged 34-59 years concluded, “[O]ur findings suggest that replacing carbohydrates with protein may be associated with a lower risk of ischemic heart disease.” And, as was also mentioned in the previous section, female mice seem to get no health benefit from protein dilution in their diets compared to male mice.

We know that women tend to lose skeletal muscle mass after menopause for a variety of reasons, including possibly hormone changes, and can get sarcopenia as a result. Higher protein intake is one suggested remedy to maintain muscle mass for post-menopausal women.

Plus, a lot of research has suggested high protein intake is not a concern for kidney function in healthy people (though it may be if you already have kidney problems), with a 2019 review arguing: 

“Concerns are frequently raised regarding the impact of high-protein diets on renal function, particularly in older persons. However, reviews of research studies reveal little or no evidence that high-protein diets cause kidney damage in healthy individuals, including those who are older.”

And it turns out negative effects of certain amino acids in protein, like methionine, seem like they can be mitigated by supplementing with glycine.

What all the above seems to suggest to me is that protein is not all bad, or all good. 

We need some of it to build muscle and survive, but maybe more of it when we’re older than when we’re younger, and when we do eat it we should try and do it in such a way as to minimize how frequently we’re activating mTOR and IGF-1—like eating it in a short window a la intermittent fasting, and combining it with resistance exercise to actually put it to good use building muscle.

But there’s still one more important aspect of protein we need to look into: its source.

Plant protein vs. animal protein: does the protein source matter?

We’ve touched on the meat vs. plant diet wars a little bit already with our posts on low-carb diets and on vegan/vegetarian diets and boy, they sure can get contentious. As a warning, this following section is probably not going to make people in either camp all that happy with me.

The question of which protein source is healthier is a complex one, and the science is not at all conclusive from what I could find.

On the one hand, most of the studies looking at the actual chemical composition of animal protein and its short-term impact on human health (like building muscle, losing fat, and improving metabolic health) seem to conclude it’s superior to plant protein in almost every way.

• It’s a more complete protein, having all the essential amino acids present compared to plant protein sources which require additional supplementation or combination with other sources
• It’s more bioavailable and digestible than plant proteins like legumes.
• It stimulates more muscle building (“anabolic response”) compared to plant proteins when consumed.
• Animal protein may better protect the bones of meat eaters from fractures compared to vegetarians and vegans.

But on the other hand, almost all of the epidemiological studies comparing animal and plant protein sources conclude that, in the long term, animal protein sources are worse for your health.

• High animal protein intake (especially from processed red meat) is positively associated with cardiovascular mortality.
• High plant protein intake is associated with lower all-cause mortality and cardiovascular disease (but not lower cancer) compared to high animal protein intake.
• Substituting animal protein with plant protein is associated with a lower risk of all‐cause mortality, cardiovascular disease mortality, and dementia mortality.

And on and on.

While, yes, epidemiological studies are far from the gold standard of scientific research given how many possible confounding variables there are (maybe vegetarians exercise more than meat eaters and that explains their healthier outcomes better than their diets, etc.) the sheer number of them that have come to similar conclusions about animal-based protein should give us pause.

As Randall Munroe likes to say, “Correlation doesn’t imply causation, but it does waggle its eyebrows suggestively and gesture furtively while mouthing ‘look over there’.”

Of course, there’s a little more nuance to the above picture.

For instance, several additional studies have indicated it may not be all animal protein that’s to blame, just processed red meat (so put down that Slim Jim!).

• Substituting out carbs for lean, unprocessed red meat doesn’t increase cardiometabolic risk even in an already healthy diet.
• Eating processed red meat, but not unprocessed red meat or poultry, is associated with a higher all-cause mortality risk.
• Replacing red meat with poultry, nuts, or fish (but not legumes) is associated with a lower risk of stroke.

In fact, several studies have found positive health effects of other specific animal proteins:

• Fish consumption is associated with lower cardiovascular risk.
• Poultry consumption is inversely associated with cancer and all-cause mortality.

But, to counter some of the initial evidence in favor of animal proteins being more complete and digestible, some good research indicates several sources of plant protein may be just as complete, bioavailable and muscle-promoting as their animal-based counterparts, particularly soy protein, which was shown to promote the same strength and muscle gains after exercise as animal proteins.

My personal conclusion from all this is that processed red meat is probably bad, but that healthy amounts of fish, poultry, and unprocessed red meat seem perfectly in line with a longevity-focused diet, while plant-based protein sources, if eaten in sufficient amounts or in the form of soy protein, can more than adequately meet nutritional and muscle-promoting needs.

So uh, you do you.

As long as you’re following a nutrient-rich diet, “Overall mortality is similar for vegetarians and comparable non-vegetarians” anyway.

What I plan on doing with protein and how much protein to eat

Taking all the above research and distilling it down, here’s what I took away as important issues to address regarding protein and longevity:

• Some amino acids in protein, specifically methionine, leucine, and tryptophan may be pro-aging.
• Protein can turn on mTOR and IGF-1, which can both age you faster if they’re on all the time or at too high levels (though also if too low for IGF-1, particularly in old age).
• But, higher skeletal muscle mass is incredibly important for longevity and for preventing sarcopenia, especially for women, and protein (plus resistance exercise) is required to build and maintain that muscle mass.
• And as we age, higher protein intake is associated with lower mortality.

So here’s my rough plan for dealing with each of those issues. Before mimicking these decisions, please note that I am a 34-year-old male and that not all of my choices will be appropriate for you:

• Counteract the dangers of methionine by taking a glycine supplement or eating foods high in glycine or glycine precursors when eating protein (for instance egg yolks are high in choline which the body synthesizes into glycine).
  • Glycine supplementation has been shown to mimic methionine restriction and extend lifespan in rats and mice, and also improves a whole host of biomarkers in humans as well. 
• I couldn’t find specific ways of mimicking leucine or tryptophan restriction (other than possibly taking the diabetes drug metformin along with a high-leucine meal) so if you’re aware of any let me know!
• Do intermittent fasting (and eventually work up to multi-day water fasts every month or quarter) to downregulate mTOR and IGF-1 after eating protein.
• Do resistance training after eating a high-protein meal to encourage muscle growth and make sure, when mTOR is active, I’m getting something productive out of it.
• Eat moderate protein (about 1.6 g/kg of lean body weight/day) until my 60s, and then increase the amount of protein after 65 (to about 1.8-2.2 g/kg/day).
• Take an IGF-1 blood test semi-annually as a way to make sure I’m not overstimulating my body’s growth pathways.

Anything I miss?

Anybody got recommendations for good muscle-building routines for a skinny guy?

J.P.

I’m the co-founder of Longevity Advice and have been passionate about radical life extension ever since I was a teenager. Formerly I was a content marketing director in the B2B software space. I’m also a sci-fi novelist, wargame rules writer, and enthusiast for cooking things in bacon fat. My sister once called me “King of the Nerds” and it’s a title I’ve been trying to live up to ever since.