Calorie restriction and rapamycin distinctly mitigate aging-associated protein phosphorylation changes in mouse...

Area of Science:

• Aging research
• Molecular biology
• Skeletal muscle physiology

Background:

• Calorie restriction (CR) and rapamycin (RM) are known to slow aging and promote health.
• CR and RM have partially overlapping effects on transcriptome and proteome.
• The impact of CR and RM on protein phosphorylation in signaling pathways remains uncompared.

Purpose of the Study:

• To compare the long-term effects of CR and RM on the phosphoproteome of mouse skeletal muscles.
• To identify novel phosphosites and analyze their tissue-specificity.
• To understand the impact of nutrient-sensing pathway inhibition on aging-related muscle changes.

Main Methods:

• Analysis of phosphoproteomes in soleus, tibialis anterior, triceps brachii, and gastrocnemius muscles of adult and aged mice.
• Mice received control, CR, or RM diets from 15 months of age.
• Reproducible detection and extensive analysis of 6960 phosphosites, including 1415 novel sites.

Main Results:

• CR and RM interventions demonstrated largely consistent but quantitatively distinct long-term effects on the phosphoproteome.
• Both interventions mitigated age-related changes in skeletal muscle to varying degrees.
• CR exhibited greater between-muscle variation in its effects compared to RM.
• Identified 1415 novel phosphosites, expanding the mouse phosphoproteome catalog.

Conclusions:

• Long-term CR and RM interventions have significant, distinct impacts on the mouse skeletal muscle phosphoproteome.
• These findings provide insights into tissue-specific effects and novel phosphosites related to aging and nutrient-sensing pathways.
• The study expands the understanding of how CR and RM modulate cellular signaling in skeletal muscle during aging.