Diet and longevityTwo recent studies in Cell Metabolism, a highly resected journal, threaten to upset the received wisdom about the optimal diet. Remember the Atkins diet and others that are based on a high-protein, low-carbohydrate, principle? Well, they may be doing more harm than good. Here are some interesting details. The first study, led by Valter Longo and his graduate student Morgan Levine, at the University of Southern California, analyzed data from 6831 adults over 50 years old who were interviewed once about their diet in the NHANES study (a national survey of health and nutrition). The highlights of their study show 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

After age 65, the effect of protein reverses course—the higher the better. So what gives? ThereDiet and longevity Diet and longevityDiet and longevityis no experimentally-backed answer. One possibility is the reduced absorption of amino acids in the older group. Another possibility: reduced proteolytic digestion of proteins to their amino acids building blocks. Another possibility, nay, probability is that both explanations are wrong and something completely unexpected is the real cause.

Nutritional studies are notoriously difficult, especially ones that rely on self-reporting. Using death records 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.

But, these results fit neatly with some molecular clues. Cutting protein intake is known to reduce levels of iGF-1 (insulin-like growth factor 1), and lower levels 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. So is it possible that the real effect of the low calorie diet on longevity is not really due to low calorie intake, but due to the lower protein intake that necessarily results from this torturous diet?

To answer this question Simpson and David Le Couteur, 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:

  • 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 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…

The finding that limiting protein intake also reduces the levels of a cellular protein called mTOR (mammalian Target of Rapamycin) is intriguing: Lower mTOR is known to extend life in mice. We 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, phenformin, a major anti-diabetes drug, is an mTOR inhibitor.

To close the loop of the IGF-1 finding of Longo et al and the mTOR findings of Stephenson and his coworkers, we now know that elevated IGF-1 causes elevation of mTOR. And that elevated protein diet causes elevation in IGF-1 and mTOR levels.

Case closed? Avoid excess proteins and gorge on pasta? Not so fast. Remember that for whatever reason, in people older than 65, higher protein in the diet is associated with a longer life span. And many observations suggest that pleasantly chubby, but not obese, older individuals actually live longer. As usual, more research is needed to untangle all those confusing findings. One experiment I would love to see: Pit a low protein diet against low-calorie diet. I have to admit to some schadenfreude (German for glee at one’s misfortune) if it turns out that those emaciated practitioners of an extreme low-calorie diet missed the pleasures of a rich chocolate cake and died hungry. All this suffering, for naught…