Calorie Restriction Greatly Slows Protein Turnover
Examination of the sweeping low-level changes in biochemistry brought on by calorie restriction continues apace: "Calorie restriction (CR) promotes longevity. A prevalent mechanistic hypothesis explaining this CR effect suggests that protein degradation, including mitochondrial autophagy, is increased, thereby removing damaged proteins. At steady state, increased catabolism must be balanced by increasing mitochondrial biogenesis and protein synthesis, resulting in faster protein replacement rates. To test this hypothesis, we measured replacement kinetics and concentrations of hundreds of proteins in vivo in long-term CR and ad libitum -fed mice ... CR reduced absolute synthesis and breakdown rates of almost all measured hepatic proteins and prolonged half-lives of most (~80%), particularly mitochondrial proteins ... Proteins with related functions exhibited coordinated changes in concentration as well as replacement rates. ... In summary, our combination of dynamic and quantitative proteomics suggest that long-term CR reduces mitochondrial biogenesis and mitophagy are reduced. Our findings contradict the theory that CR increases mitochondrial protein turnover, and provide compelling evidence that cellular fitness is accompanied by reduced global protein synthetic burden."