LONGECITY

How much of the declining function characteristic of aging is a matter of accumulated damage versus maladaptive responses to that damage? Damage to tissues alters the balance of molecules secreted by cells in those tissues, thereby changing the signaling environment both locally and throughout the body, causing other cells and tissues to react. Some of those reactions are harmful. The chronic inflammation of aging is a prominent example, the immune system serving as a broadcast network enabling dysfunction in one location in the body to contribute to harmful consequences everywhere else.

Aging brings about a myriad of degenerative processes throughout the body. A decrease in cognitive abilities is one of the hallmark phenotypes of aging, underpinned by neuroinflammation and neurodegeneration occurring in the brain. This review focuses on the role of different immune receptors expressed in cells of the central and peripheral nervous systems.

We will discuss how immune receptors in the brain act as sentinels and effectors of the age-dependent shift in ligand composition. Within this 'old-age-ligand soup,' some immune receptors contribute directly to excessive synaptic weakening from within the neuronal compartment, while others amplify the damaging inflammatory environment in the brain. Ultimately, chronic inflammation sets up a positive feedback loop that increases the impact of immune ligand-receptor interactions in the brain, leading to permanent synaptic and neuronal loss.

Link: https://doi.org/10.1042/BSR20222267