Long-Term Exercise Protects against Cellular Stresses in Aged Mice

Area of Science:

• Skeletal muscle physiology
• Aging research
• Cellular stress response

Background:

• Aging is associated with increased oxidative and endoplasmic reticulum (ER) stress in skeletal muscle.
• These stress pathways can lead to apoptosis signaling and impaired muscle function.
• The role of long-term exercise in mitigating these age-related cellular changes requires further investigation.

Purpose of the Study:

• To investigate the impact of aging and long-term voluntary wheel-running on heat shock protein (HSP) expression, redox regulation, and ER stress markers.
• To compare these markers in the tibialis anterior (T.A.) and soleus muscles of young, old-sedentary, and old-exercising mice.

Main Methods:

• Mice were divided into young (3-month-old), old-sedentary (24-month-old), and old-exercise (24-month-old) groups.
• The old-exercise group engaged in voluntary wheel-running from 3 to 24 months of age.
• Expression levels of HSPs, redox regulators (thioredoxin-interacting protein [TxNiP], thioredoxin-1 [TRX-1]), and ER stress markers (CHOP, GRP78) were analyzed in T.A. and soleus muscles.

Main Results:

• Aging elevated TxNiP, decreased the TRX-1/TxNiP ratio, and increased CHOP in both muscles, indicating redox imbalance and ER stress-related apoptosis signaling.
• GRP78 was selectively elevated in the T.A. muscle of aged mice.
• Long-term exercise reduced TxNiP, increased the TRX-1/TxNiP ratio in soleus muscle, and upregulated HSP70 while reducing CHOP in the soleus muscle of aged mice.

Conclusions:

• Aging induces oxidative stress and activates ER stress-related apoptosis signaling in skeletal muscle.
• Life-long wheel-running exercise improves redox regulation and ER stress adaptation in aged mice.
• Exercise attenuates ER stress-related apoptosis signaling, suggesting a protective effect against age-related cellular stress in skeletal muscle.