Network Rewiring in the Aging Immune System: From Chronic Inflammation to Age-Related Pathologies.

Area of Science:

• Immunology
• Gerontology
• Systems Biology

Background:

• Aging significantly alters immune function, leading to increased susceptibility to infections, reduced vaccine efficacy, and heightened risk of age-related diseases (ARDs).
• Immune aging is characterized by immunosenescence (age-related decline in immunity) and inflammaging (chronic, low-grade inflammation).
• These changes represent a systems-level reprogramming of immune networks, disrupting inflammatory response phases.

Purpose of the Study:

• To review recent advances in understanding the mechanisms of immune dysfunction during aging.
• To focus on the interplay between chronic inflammation, failed resolution, and defective repair in immune aging.
• To discuss how immune aging contributes to major ARDs and highlight potential therapeutic strategies.

Main Methods:

• Literature review of recent advances in immunology, gerontology, and systems biology.
• Analysis of mechanisms underlying immune dysfunction, including innate and adaptive immunity, immunometabolism, and cellular senescence.
• Discussion of immune-tissue interactions and their role in inflammaging and ARDs.

Main Results:

• Aging impairs the resolution of inflammation, efferocytosis, and responsiveness to pro-resolving signals, leading to persistent inflammation and tissue damage.
• Alterations in innate and adaptive immunity, immunometabolism, cellular senescence, and immune-tissue interactions drive inflammaging.
• Immune aging is a significant contributor to ARDs such as cancer, neurodegenerative diseases, and cardiometabolic diseases.

Conclusions:

• Immune aging is a complex, systems-level phenomenon involving the reinforcement of chronic inflammation, failed resolution, and defective repair.
• Understanding these mechanisms is crucial for developing interventions to combat ARDs.
• Targeting immune aging presents a modifiable strategy for promoting healthy aging and extending healthspan.