Corticotropin-releasing factor (CRF) in brain aging: from mitochondrial dysfunction to inflammaging

Area of Science:

• Neuroendocrinology
• Molecular Biology
• Gerontology

Background:

• Aging is a complex biological process influenced by neuroendocrine stress mechanisms.
• The corticotropin-releasing factor (CRF) signaling pathway is implicated in connecting stress responses to aging.
• CRF exerts effects via its receptors, CRFR1 and CRFR2, with CRFR1 mediating primary effects and CRFR2 having a modulatory role.

Purpose of the Study:

• To systematically review and integrate research on the CRF signaling pathway and aging hallmarks.
• To explore the proposed "CRF-mitochondrial dysfunction-inflammation-aging" axis.
• To provide a theoretical foundation for understanding stress-driven aging and identifying intervention targets.

Main Methods:

• Literature review and synthesis of preclinical evidence.
• Focus on the molecular mechanisms linking CRF signaling to mitochondrial dysfunction, inflammation, and aging.
• Analysis of the proposed "CRF-mitochondrial dysfunction-inflammation-aging" axis.

Main Results:

• Excessive CRF signaling is linked to mitochondrial dysfunction, including impaired dynamics and biogenesis.
• Mitochondrial damage leads to reactive oxygen species (ROS) overproduction and DNA damage.
• DAMPs released from damaged mitochondria activate immune pathways, potentially causing chronic inflammation and cellular senescence.

Conclusions:

• The CRF signaling pathway plays a critical role in mediating stress-induced aging.
• Mitochondrial dysfunction and chronic inflammation are key downstream consequences of dysregulated CRF signaling.
• Elucidating the CRF-mitochondrial dysfunction-inflammation-aging axis offers potential therapeutic targets for mitigating stress-accelerated aging.