Late-Life Aerobic Exercise Attenuates DNA Damage and Telomere Dysfunction in Non-Atheroprone but Not in Atheroprone...

Area of Science:

• Cardiovascular Biology
• Aging Research
• Cellular Biology

Background:

• Cellular senescence, driven by DNA damage response (DDR) and telomere dysfunction, significantly contributes to arterial aging.
• Aerobic exercise in late life is known to mitigate arterial aging, but its effects on DDR and telomere dysfunction across different aortic shear stress regions remain unclear.

Purpose of the Study:

• To investigate the impact of late-life aerobic exercise on DDR and telomere dysfunction in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) within aortic regions with varying shear stress patterns.
• To determine if exercise benefits are uniform across atheroprone and non-atheroprone aortic regions.

Main Methods:

• Old male C57BL6 mice were subjected to 16 weeks of voluntary wheel running (VWR) at low, moderate, or high intensities.
• DNA damage response (DDR) and telomere dysfunction were assessed in ECs and VSMCs from different aortic regions.
• Comparisons were made between control and VWR groups, and across varying exercise volumes.

Main Results:

• No significant differences in DDR or telomere dysfunction were observed in ECs and VSMCs in control, low, or moderate running groups across aortic regions.
• High running (HR) intensity exercise mitigated EC DDR and telomere dysfunction specifically in non-atheroprone aortic regions.
• These improvements in ECs were independent of telomere length and not observed in VSMCs.

Conclusions:

• Late-life aerobic exercise, particularly at higher volumes, selectively reduces DDR and telomere dysfunction in ECs within non-atheroprone aortic regions.
• The benefits are exercise volume-dependent and occur independently of changes in telomere length.
• These findings highlight a targeted effect of exercise on vascular aging mechanisms in specific aortic locations.