Sulfur amino acid restriction–induced changes in redox-sensitive proteins are associated with slow protein synthesis rates
Optimal maintenance of protein quality is critical for proper cellular functions. Protein turnover (PT) is a critical contributor to protein integrity and serves other functions, such as providing amino acids during starvation or dietary deficiency. By controlling the rates of synthesis and degradation of specific proteins, PT can also help regulate a number of physiological processes, including inflammation, immunity, cholesterol metabolism, and gene transcription. Thus, a decline in PT results not just in the accumulation of damaged and nonfunctional proteins but also has wider implications for overall healthspan and lifespan.
The mechanisms underlying lifespan extension by sulfur amino acid restriction (SAAR) are still unclear. Caloric restriction and SAAR are the two dietary interventions that have shown to extend lifespan in rodent models. A significant number of mechanistic studies suggest that caloric restriction increases PT by increasing autophagy and proteasomal functions. However, some recent studies in C. elegans suggest that lower rates of protein synthesis are associated with lifespan extension. Depending on the biological context, both an increase and a decrease in protein synthesis rates could lead to increased protein quality and contribute to lifespan extension. An increase in protein synthesis would result in less damage under conditions of oxidative stress, but would also cause energy usage. Slower protein synthesis, as a result of SAAR, would lead to a decrease of energy usage. This saved energy could then be used for other cellular functions.
Restriction of protein synthesis not only minimizes cell senescence but also increases the resistance to environmental damage, including UV radiation, oxidative stress, and starvation. These advantages, when coupled with reduced oxidative insult, as shown in previous studies, might lead to a significant improvement in hepatic proteostasis. Additional studies are required to confirm whether slower rates of protein synthesis result in improved proteostasis and whether it is a contributing factor in SAAR-induced lifespan extension.