Organ Specificity and Commonality of Epigenetic Aging in Low- and High-Running Capacity Rats

Area of Science:

• Gerontology
• Epigenetics
• Molecular Biology

Background:

• Epigenetic drift, or age-related DNA methylation changes, is crucial in aging and disease.
• The interplay between exercise, epigenetics, and aging, including molecular mechanisms, remains unclear.

Purpose of the Study:

• To investigate the link between cardiorespiratory fitness (CRF), epigenetic aging, and gene promoter methylation across multiple organs.
• To explore organ-specific epigenetic responses to varying levels of CRF in aged rats.

Main Methods:

• Utilized selectively bred low- and high-capacity runner (LCR and HCR) aged rats.
• Analyzed DNA methylation patterns, global methylation, methylation entropy, and promoter methylation of specific genes in multiple organs.
• Applied epigenetic clocks trained on rat blood-derived data.

Main Results:

• Epigenetic clocks did not differentiate CRF levels across organs.
• Observed organ-specific differences in DNA methylation and entropy between LCR and HCR rats, contrasting with age-related blood changes.
• Soleus muscle showed the most significant CRF-related promoter methylation differences; seven genes were consistently affected across all four organs.
• Soleus muscle exhibited higher age acceleration than heart and hippocampus but lower than the large intestine, indicating organ-specific aging patterns.

Conclusions:

• Cardiorespiratory fitness (CRF) is associated with epigenetic aging in both organ-specific and common ways.
• Findings underscore the organ-specific nature of epigenetic aging, crucial for validating anti-aging interventions.