Cognitive decline associated with aging is increasingly recognized as a multifaceted issue, influenced not only by neural function deterioration but also by alterations in immune niches surrounding the brain and changes within the peripheral immune system.

The immune system is essential for various functions beyond pathogen defense, including tissue maintenance, damage repair, and debris clearance, highlighting its importance in overall health.

Recent research has reshaped our understanding of the relationship between the brain and the immune system, revealing that neurons depend on the adaptive immune system for support and effective communication.

Historically, the immune system was viewed as having little impact on a healthy central nervous system (CNS), often considered detrimental in brain disorders due to the concept of 'CNS immune privilege.'

The existence of the blood-brain barrier (BBB) and the previously assumed absence of a lymphatic system in the CNS reinforced the belief that the immune system had minimal interaction with brain health.

Interactions between the immune and nervous systems predominantly occur at the brain's borders, where immune cells are concentrated, playing a critical role in brain health.

Chronic inflammation has been shown to adversely affect cell behavior, contributing to immune aging and unresolved inflammatory signaling that can harm tissues.

As aging alters the function of the brain's borders and the composition of immune cells, it impacts the signals sent to the brain, further contributing to cognitive decline.

The concept of brain fitness is now linked to immune fitness, emphasizing that lifestyle choices can significantly influence this relationship.

A deeper understanding of the communication pathways between the immune and nervous systems may pave the way for strategies aimed at immune rejuvenation, potentially slowing or halting the aging process of the brain.