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

Hamed Mirzaei

Jorge A. Suarez

Valter D. Longo

Email the author Valter D. Longo

DOI: http://dx.doi.org/10.1016/j.tem.2014.07.002

Article Info

Highlights

•Protein or AA restriction has been shown to be as potent as calorie restriction in extending healthspan in multiple model organisms.
•AA restriction affects lifespan partly through modulation of the amino acid sensing pathways TOR and GCN2.
•Human epidemiological studies highlight the detrimental effects of high protein diets, in particular animal-derived protein sources in contrast to plant-based sources.
•Epidemiological studies indicate that low protein diets are associated with lower risk of chronic and age-related diseases such as CVDs, diabetes, and cancer.

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.