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      Aging brain: exploring the interplay between bone marrow aging, immunosenescence, and neuroinflammation

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          Abstract

          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.

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            Cellular senescence is a tumor-suppressive mechanism that permanently arrests cells at risk for malignant transformation. However, accumulating evidence shows that senescent cells can have deleterious effects on the tissue microenvironment. The most significant of these effects is the acquisition of a senescence-associated secretory phenotype (SASP) that turns senescent fibroblasts into proinflammatory cells that have the ability to promote tumor progression.
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              Chronic inflammation in the etiology of disease across the life span

              Although intermittent increases in inflammation are critical for survival during physical injury and infection, recent research has revealed that certain social, environmental and lifestyle factors can promote systemic chronic inflammation (SCI) that can, in turn, lead to several diseases that collectively represent the leading causes of disability and mortality worldwide, such as cardiovascular disease, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease and autoimmune and neurodegenerative disorders. In the present Perspective we describe the multi-level mechanisms underlying SCI and several risk factors that promote this health-damaging phenotype, including infections, physical inactivity, poor diet, environmental and industrial toxicants and psychological stress. Furthermore, we suggest potential strategies for advancing the early diagnosis, prevention and treatment of SCI.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/464258Role: Role: Role: Role: Role:
                Role: Role: Role: Role:
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                04 April 2024
                2024
                : 15
                : 1393324
                Affiliations
                [1]Max Planck Institute for Human Development, Center for Lifespan Psychology , Berlin, Germany
                Author notes

                Edited by: Junchi He, Upstate Medical University, United States

                Reviewed by: Xuchao Lyu, Stanford University, United States

                Cuncai Guo, Washington University in St. Louis, United States

                Dong Yang, The Scripps Research Institute, United States

                *Correspondence: Ludmila Müller, lmueller@ 123456mpib-berlin.mpg.de
                Article
                10.3389/fimmu.2024.1393324
                11024322
                38638424
                7eb2f760-eaa4-471b-afe6-9bc32cc45b14
                Copyright © 2024 Müller and Di Benedetto

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 28 February 2024
                : 25 March 2024
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 90, Pages: 10, Words: 4671
                Funding
                The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.
                Categories
                Immunology
                Mini Review
                Custom metadata
                Multiple Sclerosis and Neuroimmunology

                Immunology
                aging,brain,bone marrow,neuroinflammation,immunosenescence,inflammaging,neurological disorders
                Immunology
                aging, brain, bone marrow, neuroinflammation, immunosenescence, inflammaging, neurological disorders

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