Diet and longevityTwo studies, one in humans and one in mice, made a big splash when they were published in the highly respected journal, Cell MetabolismThe results challenged the perceived wisdom about the optimal amount of protein in the diet. Let’s take a look at them.


The human study

The first study, led by Valter Longo and his graduate student Morgan Levine, at the University of Southern California, analyzed data from 6,831 U.S. adults aged 50 years and older. The data came from the Third National Health and Nutrition Examination Survey (NHANES III). The highlights of their study showed that:

  • High protein intake is linked to increased cancer, diabetes, and overall mortality.
  • High IGF-1 levels increased the relationship between mortality and high protein.
  • Higher protein consumption may be protective for older adults.
  • Plant-derived proteins are associated with lower mortality than animal-derived proteins.

Although high protein diets in middle age folks are linked to a higher mortality, things were different for seniors. The researchers found that in oldsters, those over 65, a high protein diet was linked to lower mortality. So what gives?

There is no experimentally-backed answer, but it is theoretically possible that there is reduced absorption of amino acids in the older group. Another possibility is there could be reduced proteolytic digestion of proteins to their amino acids building blocks. And yet another possibility, nay, probability is that both explanations are wrong and something completely unexpected is the real cause.

Now, nutritional studies are problematic, especially ones that rely on self-reporting, such as the NHANES survey. Using death records to determine cause of death, as was done in this study, is also problematic. Did the person die of heart disease, or was that secondary to type 2 diabetes? Frequently, death records are not sufficiently complete to tell the whole story.


The role of IGF-1

Let’s leave study methodology aside for now because these results actually fit neatly with some biochemical clues. Cutting dietary protein intake is known to reduce levels of insulin-like growth factor 1 (IGF-1), and lower levels of this regulatory protein are correlated with longer life span.

Longo and his team tested stored samples from the participants of the NHANES survey and found that higher protein intake correlated with higher IGF-1 levels. This finding raises the question of whether beneficial effect of a severely caloric restricted diet on longevity is really due to lower protein intake as opposed to consuming fewer calories.


The mouse study

To answer this question, Stephen Simpson, David Le Couteur, and colleagues at the University of Sidney, assigned 858 mice to one of 25 diets with different mixes of protein, carbohydrates, fats, and fiber. The lucky participant mice were allowed to eat ad libitum, or “all you can eat” in English. And, the highlights of the results are as follows:

  • Food intake is regulated primarily by dietary protein and carbohydrate
  • Low-protein, high-carbohydrate diets are associated with the longest lifespans
  • Energy reduction from high-protein diets or dietary dilution (with fiber) does not extend life
  • Diet influences hepatic mTOR (more on this later) via branched-chain amino acids and glucose

Of course, mice are not human, and their metabolism differs from ours. Also, this experiment was done on one strain of mice. There are known metabolic differences among the different strains. Yet…

Here is a graphical summary of the findings of the two studies:

Graphic of results of two Cell Metabolism studies on dietary protein and health
Photo credit: metabolism



The finding that a high protein diet increases the activation of a hepatic mTOR (mammalian Target of Rapamycin) is intriguing. It is known that lower mTOR activation is associated with extended life in mice. I have written about this protein’s centrality in cell metabolism and its amazing history in the past. This is not just an “academic curiosity.”

Several chemotherapeutic agents in the treatment of several cancers are mTOR inhibitors. Also, metformin, a major anti-diabetes drug, is also a mTOR inhibitor.

To close the loop of the IGF-1 finding of Longo et al. and the mTOR findings of Simpson and his coworkers, we now know that elevated levels IGF-1 are associated with activation mTOR. And that elevated protein diet is associated with both the elevation of IGF-1 and mTOR activation.


So what should we do?

Can you guess his biological age/ Source; Wikimedia Commons
via Wikimedia Commons

So, if you followed all of that, you may be asking so what should I do? Avoid excess proteins and gorge on pasta? Aren’t we all supposed to be eating low carb? Does that mean substituting both with fat? No way!

And, to add to the confusion, remember that for whatever reason, for people older than 65, higher protein in the diet was associated with a longer life span.

So, as usual, as we, scientists, like to conclude, more research is needed to untangle all those confusing findings. In the meanwhile, my friends, remember the old saying, “moderation in all things.”

Dov Michaeli, MD, PhD
Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.



Please enter your comment!
Please enter your name here

This site uses Akismet to reduce spam. Learn how your comment data is processed.