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Aging Brain: Interplaying between bone marrow aging, immunosenescence, and neuroinflammation

Our bone marrow and immune system undergo significant changes as we age, impacting our brain health. This fascinating mini-review by Müller and Di Benedetto dives deep into how aging bone marrow contributes to immunosenescence and neuroinflammation, which are key players in age-related neurological disorders.

Key Points:


1. Bone Marrow Aging and Immune Cell Dysfunction:

     Hematopoietic Stem Cells (HSCs): With age, HSCs lose their self-renewal capacity and differentiation potential, leading to a decline in immune cell production.

    Altered Niche Composition: Aging changes the bone marrow environment, disrupting the balance of supportive cells like mesenchymal stromal cells and osteoblasts.

    Increased Adiposity: More fat cells in the bone marrow displace essential hematopoietic cells, impairing immune function.


2. Molecular Mechanisms:

     Pro-inflammatory Cytokines: Aging increases the production of cytokines like IL-6, TNF-α, and IL-1β, which disrupt hematopoiesis and promote a pro-inflammatory state.

    Oxidative Stress: Higher levels of reactive oxygen species (ROS) activate pathways that enhance pro-inflammatory cytokine production.

    Cellular Senescence: Accumulation of senescent cells within the bone marrow contributes to chronic inflammation and further disrupts immune function.


3. Neuroinflammation and Brain Health:

     Impact on Neurons: Pro-inflammatory cytokines from aged bone marrow affect neuronal health, leading to increased neuroinflammation and synaptic dysfunction.

    Cognitive Decline: Studies show that aged HSCs transplanted into young mice decrease hippocampal neurogenesis and cognitive functions.


Potential Therapies: Research on young blood and bone marrow transplants shows promise in reversing some aging effects, improving synaptic density, and reducing microglial activation.

Müller, L. and S. Di Benedetto, Aging brain: exploring the interplay between bone marrow aging, immunosenescence, and neuroinflammation. Frontiers in Immunology, 2024. 15.


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