Protein and amino acid restriction, aging and disease: from yeast to humans

Abstract

Many of the effects of dietary restriction (DR) on longevity and health span in model organisms have been linked to reduced protein and amino acid (AA) intake and the stimulation of specific nutrient signaling pathways. Studies in yeast have shown that addition of serine, threonine, and valine in media promotes cellular sensitization and aging by activating different but connected pathways. Protein or essential AA restriction extends both lifespan and healthspan in rodent models. In humans, protein restriction (PR) has been associated with reduced cancer, diabetes, and overall mortality. Thus, interventions aimed at lowering the intake of proteins or specific AAs can be beneficial and have the potential to be widely adopted and effective in optimizing healthspan.

Lysine Restriction Affects Feed Intake and Amino Acid Metabolism via Gut Microbiome in Piglets

“…Meanwhile, feed intake was significant higher in the lysine-restricted group than that in the control group, which is contrast with the effect of protein restriction on feed intake [1]. These results concluded that lysine limitation failed to contribute to the merit of protein restriction.…”

“…Dietary restriction is a promising therapeutic potential for preventing aging-related diseases and extending healthspan via mediating feeding behavior and metabolic reprograming, especially for protein restriction [1-4]. Lysine serves as a key building block for protein synthesis and has been classified as an essential amino acid in humans and animals [5-7].…”

Protective effects of short-term dietary restriction in surgical stress and chemotherapy

“…Notably, glucose metabolism alone does not supply all the required building blocks necessary for cell-proliferation and cancer cells therefore depend on the availability of amino acids, particularly glutamine, as a nitrogen source (Vander Heiden et al, 2009). In line with this requirement of cancer cells, protein/amino acid restriction have been demonstrated to delay the onset of many aging-related diseases, including cancer, and increase longevity (Mirzaei et al, 2014). …”

An increased need for dietary cysteine in support of glutathione synthesis may underlie the increased risk for mortality associated with low protein intake in the elderly

“…The favorable impact of mid-life protein restriction might be anticipated, given that diets restricted in proteins or essential amino acids, consumed in unrestricted amounts, have been shown to boost mean and maximal lifespans in rodents (Mirzaei et al 2014;Sanchez-Roman and Barja 2013). A recent study evaluating the impact of ad libitum diets of widely varying macronutrient composition on longevity in mice found that the highest mean and maximal lifespan was seen in mice consuming a diet providing 5 % protein and 75 % carbohydrates (Solon-Biet et al 2014).…”