The inner fire: the shifting paradigm of complement system in aging
Paola Triggianese1,2,3, David Della-Morte1,3,4
1Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
Frontiers in Immunology
|April 30, 2026
Summary
The aging complement system (CS) shifts from causing inflammation to potentially protecting against neuroinflammation and autoimmunity in the elderly. Understanding this dual role is key for future therapies.
Area of Science:
- Immunology
- Aging Research
- Inflammation Biology
Background:
- The complement system (CS) is crucial for innate immunity, bridging to adaptive immunity and maintaining homeostasis.
- CS dysregulation is linked to infections, autoimmunity, and chronic inflammation.
- Aging involves persistent low-grade inflammation ('inflammaging') and continuous CS activation, potentially contributing to age-related diseases.
Purpose of the Study:
- To review the dual role of the aging complement system.
- To explore the potential protective effects of age-related CS dysregulation in the elderly.
- To understand CS modulation of immunosenescence, neuroinflammation, and autoimmunity.
Main Methods:
- Literature review of emerging evidence on complement system function in aging.
- Synthesis of research on CS modulation of immune responses in elderly populations.
- Exploration of the complex network involving immunosenescence, neuroinflammation, and autoimmunity.
Main Results:
- Aging shifts the complement system's role, potentially leading to chronic inflammation ('inflammaging').
- Elevated CS proteins in the elderly may offer protection against neuroinflammation and autoimmune diseases.
- The aging CS exhibits a complex, potentially protective, immunomodulatory function.
Conclusions:
- The aging complement system presents a 'Janus-faced' role, mediating inflammation and potentially providing protective immunomodulation.
- Understanding the shift in CS function during aging is vital for developing targeted therapeutic strategies.
- Future research should focus on harnessing the protective aspects of CS dysregulation while mitigating its inflammatory effects.
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