Tracing Contributions to Neuroinflammation Back to the Bone Marrow
In today's open access paper, researchers discuss the role of bone marrow aging in the chronic inflammation observed in the aging brain. This inflammation is clearly of great importance in the onset and development of neurodegenerative conditions such as Alzheimer's disease; it is disruptive to the function of the brain. The immune system of the body originates in the hematopoietic cell populations of bone marrow, where cells of the innate immune system are created, as well as the thymocyte precursors to adaptive immune cells. With age, the production of immune cells becomes biased towards innate immune cells (myeloid cell lineages) over adaptive immune cells (lymphoid lineage), but this is far from the only change that takes place.
The immune system of the brain is distinct from that of the body, and originates from different progenitor populations established during early development. Microglia of the central nervous system, for example, are analogous to the macrophages found in the rest of the body, but are thought to originate in the yolk sac during embryonic growth. Still, the immune system of the brain is influenced by that of the body, both by the passage of inflammatory signal molecules, and by the transport of some small number of immune cells into the brain. This transfer appears to increase with age, either due to dysfunction of the blood-brain barrier, or as an adaptive process in response to some aspect of aging. Regardless, while the immune system of the brain is distinct, it is far from isolated from the state of the body, and is thus affected by aspects of aging taking place in the bone marrow.
Aging is a complex process characterized by a myriad of physiological changes, including alterations in the immune system termed immunosenescence. It exerts profound effects on both the bone marrow and the central nervous system, with significant implications for immunosenescence in neurological contexts. Our mini-review explores the complex relationship between bone marrow aging and its impact on immunosenescence, specifically within the context of neurological diseases.
The bone marrow serves as a crucial hub for hematopoiesis and immune cell production, yet with age, it undergoes significant alterations, including alterations in hematopoietic stem cell function, niche composition, and inflammatory signaling. These age-related shifts in the bone marrow microenvironment contribute to dysregulation of immune cell homeostasis and function, impacting neuroinflammatory processes and neuronal health.
In our review, we aim to explore the complex cellular and molecular mechanisms that link bone marrow aging to immunosenescence, inflammaging, and neuroinflammation, with a specific focus on their relevance to the pathophysiology of age-related neurological disorders. By exploring this interplay, we strive to provide a comprehensive understanding of how bone marrow aging impacts immune function and contributes to the progression of neurological diseases in aging individuals. Ultimately, this knowledge can hold substantial promise for the development of innovative therapeutic interventions aimed at preserving immune function and mitigating the progression of neurological disorders in the elderly population.