Immune Aging as a Driver of Brain Aging
The immune system isn't just a means to defend against pathogens and potentially cancerous cells. It is also intimately involved in tissue function and maintenance, in regeneration from damage, in clearing debris, and communicates at a distance throughout the body via a panoply of signaling molecules. Beyond these functions, which are affected by the age-related decline of the immune system, there is also the point that chronic inflammation changes cell behavior for the worse. A sizable part of the problem of immune aging is the rise of unresolved inflammatory signaling and its effects on tissues.
For decades, the general assumption was that the immune system had no impact on the healthy central nervous system (CNS) and was often regarded as exclusively harmful in the context of brain disorders. This understanding was largely based on the concept of "CNS immune privilege," supported by the presence of the blood-brain barrier (BBB) and the presumed absence of a lymphatic system in the CNS. More recently, a transformed understanding of brain-immune relationships has been established, which opened new avenues in the field of neuroscience, highlighting the fact that neurons require the assistance and tuning provided by the adaptive immune system in the form of novel communication routes between the two systems. According to this view, brain fitness depends on immune fitness, which in turn is modified by our lifestyle.
This intricate dance between the immune and the nervous systems takes part primarily at the brain's borders, where immune cells are concentrated. In aging, the function of these borders and the immune cell composition change, thereby altering the signals transmitted to the brain, negatively impacting brain function. This implies that the cognitive decline observed in aging is not caused solely by the decline in neural function but also by the age-dependent alterations in both the immune niches surrounding the brain and the peripheral immune system. Understanding this lifelong communication route and identifying those immune processes that become defective in aging could aid in developing potential strategies for immune system rejuvenation as a means to slow down or even arrest brain aging.