Calorie restriction does not increase short-term or long-term protein synthesis

Area of Science:

• Aging and Metabolism
• Molecular Biology
• Nutritional Science

Background:

• Caloric restriction (CR) is linked to lifespan extension, with increased protein synthesis proposed as a key mechanism.
• However, the tissue-specific and feeding-dependent effects of CR on protein synthesis remain unclear.
• Understanding these dynamics is crucial for elucidating CR's impact on aging and metabolism.

Purpose of the Study:

• To investigate whether CR uniformly increases protein synthesis across tissues and feeding states.
• To determine if any observed increase in protein synthesis is attributable to the anabolic effects of feeding.
• To examine the relationship between CR, protein synthesis, and mammalian target of rapamycin (mTOR) signaling.

Main Methods:

• In vivo measurement of protein synthesis rates in mice subjected to lifelong ad libitum (AL) feeding versus CR.
• Short-term (4 hours) and long-term (6 weeks) CR protocols were employed.
• Analysis of liver and heart tissue for mTOR signaling pathway activation.

Main Results:

• CR did not elevate mixed protein synthesis rates over the long term or in response to acute feeding.
• Liver mitochondrial protein synthesis was significantly lower in CR mice compared to AL mice.
• Mammalian target of rapamycin (mTOR) signaling was suppressed in the liver and heart of CR mice, suggesting energetic stress.

Conclusions:

• Caloric restriction does not appear to extend lifespan by increasing overall protein synthesis.
• Protein synthesis is maintained in CR mice despite suppressed mTOR signaling, indicating adaptive mechanisms.
• The findings challenge the prevailing hypothesis linking CR-mediated lifespan extension directly to enhanced protein synthesis.