Nutrient sensing – a cell’s capacity to recognize and respond to fuel sources – plays a critical role in human health, ultimately influencing the aging process and susceptibility to age-related disease. Findings from a recent study suggest that dietary interventions exert powerful effects on proteins produced in the liver, fundamentally “reprogramming” nutrient-sensing pathways.

Multiple studies have investigated the possibility that dietary strategies or drugs can alter nutrient-sensing pathways to improve metabolic health and extend lifespan. For example, robust evidence indicates that intermittent fasting and calorie restriction prolong lifespan in rodents and monkeys. Other findings suggest that altering dietary composition, such as increasing or decreasing protein, fat, or carbohydrate content, also influences longevity. Similarly, many drugs and bioactive compounds have demonstrated longevity-promoting qualities.

The study investigators assessed the effects of various diets and drugs on liver protein production in mice, using the Geometric Framework for Nutrition, a research tool that identifies links between diet, health, and disease. Diets included in the analysis varied in terms of overall nutrient content and calories. Drugs under study included metformin (an anti-diabetes drug), rapamycin (an anti-parasitic drug), and resveratrol (a bioactive compound derived from certain fruits and vegetables).

Diets with lower caloric content accelerated production of proteins required for overall protein synthesis (particularly genes for a cellular machine called the spliceosome). As dietary protein content increased, oxidative stress in mitochondria increased. Higher protein content also increased SLC25A51, a cellular protein involved in the transport of nicotinamide adenine dinucleotide (NAD+). NAD+ participates in many aspects of metabolism, and its depletion has been implicated in the onset and progression of metabolic dysregulation. Interestingly, anti-aging drugs diminished the effects of diet. For example, metformin and rapamycin impaired mitochondrial responses to protein, and resveratrol decreased the response to fats and carbohydrates.

These findings suggest that diet dramatically influences cellular processes involved in metabolism and longevity and is superior to current anti-aging drugs and compounds. Learn more about dietary strategies, drugs, and bioactive compounds that may promote longevity in our overview articles about caloric restriction, time-restricted eating, metformin, and resveratrol.

• Link to study abstract.

• Learn more about dietary strategies that may promote longevity in this episode featuring Dr. Valter Longo.