Aging Impairs Mitochondrial Function and Mitophagy and Elevates Interleukin 6 Within the Cerebral Vasculature

Area of Science:

• Neuroscience
• Gerontology
• Vascular Biology

Background:

• The blood-brain barrier (BBB) is vital for brain health, but its integrity declines with age.
• Mechanisms linking aging, mitochondrial dysfunction, and BBB impairment remain unclear.
• Mitochondrial dysfunction can trigger inflammatory responses, potentially affecting the BBB.

Purpose of the Study:

• To investigate how aging affects mitochondrial function, mitophagy, and inflammation in cerebral vasculature.
• To determine the correlation between these changes and BBB integrity.
• To explore the role of Interleukin-6 (IL-6) in age-related BBB dysfunction.

Main Methods:

• Isolated cerebral vessels from young and aged mice.
• Assessed mitochondrial function, senescence markers (p16), and mitophagy proteins (Parkin, Nix).
• Utilized mitophagy reporter mice and treated vessels with rotenone, IL-6, and mitochondrial N-formyl peptides.

Main Results:

• Aged mice showed increased senescence, impaired mitochondrial function, and BBB leak.
• Aging reduced the capacity for mitophagy and increased IL-6 and stimulator of interferon genes expression.
• IL-6 exacerbated mitochondrial dysfunction and mitophagy, while its inhibition improved mitochondrial function in aged vessels. Mitochondrial N-formyl peptides increased IL-6 and Parkin, reducing Claudin-5.

Conclusions:

• Aging compromises cerebrovascular mitochondrial function and mitophagy, increasing IL-6 levels.
• These age-related alterations in cerebral vessels likely contribute to BBB impairment.
• Targeting mitochondrial dysfunction and IL-6 signaling may offer strategies to preserve BBB integrity and cerebrovascular health during aging.