Reviewing What is Known of the Ability of Reduced Protein Intake to Slow Aging
Reduced protein intake is robustly demonstrated to improve long-term health and slow aging in animal studies, and the human evidence is supportive. Many of the sensors and triggers of the beneficial metabolic response to fasting and other forms of calorie restriction react to protein availability specifically, increasing cellular maintenance activities to improve cell and tissue function. "Protein" in dietary matters usually means essential amino acids, those not manufactured in the body. The actual definition that leads to a measurement reported on a food label is more complicated than this, but is still largely an attempt to reflect availability of essential amino acids per ingested unit of a given food type.
As researchers point out in today's open access paper, despite the strong evidence for lower protein intake to be favorable over the long term, government bodies continue to recommend higher protein intake, driven by ongoing concerns over the prevalence of obesity (high protein intake tends to reduce overall calorie intake) and frailty (high protein intake tends to increase muscle growth). There is also the point that not all protein sources are the same from a health perspective. For example, obtaining protein from plant sources is well established to produce better effects on health than protein from animal sources. Further, the intake level of different essential amino acids have different, overlapping effects on health. There is quite a deep rabbit hole underneath the simple point that lower protein intake should be considered beneficial, and researchers here attempt to explore some of it.
Reviewing What is Known of the Ability of Reduced Protein Intake to Slow Aging
In rodents, the ratio of dietary macronutrients profoundly impacts lifespan, with low-protein, high-carbohydrate diets extending lifespan and improving metabolic health. A low-protein diet, also referred to as protein restriction (PR), is a robust geroprotective regimen that lowers total dietary protein intake while still meeting nutritional needs. PR improves healthspan and increases the lifespan of yeast, flies, and rodents. Despite these findings, human dietary recommendations generally suggest increasing protein intake. While the official Recommended Dietary Allowance (RDA) for protein is 0.8 g/kg of bodyweight regardless of sex or age, intakes of 1.0-1.2 g protein/kg of bodyweight are routinely recommended for individuals over the age of 65 to prevent sarcopenia and frailty, and the most recent Dietary Guidelines for America suggest 1.2-1.6 g protein/kg of body weight. These recommendations are supported by studies finding that short-term high protein diets promote weight loss, largely by promoting satiety and reducing food intake in highly compliant subjects.
However, accumulating evidence challenges the idea that higher protein intake is beneficial. Human association studies have found that high-protein diets are associated with an increased risk of diabetes, cancer, and mortality, as well as an increased risk of death due to cardiovascular events. An analysis of the National Health and Nutrition Examination Survey (NHANES) data found that higher protein consumption correlates with increased mortality and age-associated disease incidence, including diabetes.
Randomized controlled trials (RCTs) support the metabolic benefits of PR in humans. We reported that individuals consuming a low-protein diet for 43 days exhibited decreased body weight and fat mass and reduced fasting blood glucose despite increased caloric intake, mirroring our findings in rodents. A recent study in lean men found that a 5-week PR intervention improves insulin sensitivity and increases energy expenditure.
In this review, we detail, for the first time, the hallmarks of PR: improved metabolic health, induction of nutrient-sensing pathways, decreased senescence, improved mitochondrial function, altered epigenome, and the promotion of healthy aging. Taken together, these hallmarks describe the robust impact of PR on aging-related phenotypes. While these hallmarks are seen in most organisms on dietary PR, some variations exist based on biological sex or animal strain. The hallmarks discussed in this review are highly interconnected, providing a firm foundation for future exploration on the causal nature of these hallmarks to understand which hallmarks are most important in orchestrating the response to PR.