Phagocyte Dysfunction, Tissue Aging and Degeneration
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Immunologically-silent phagocytosis of apoptotic cells is critical to maintaining tissue homeostasis and innate immune balance. Aged phagocytes reduce their functional activity, leading to accumulation of unphagocytosed debris, chronic sterile inflammation and exacerbation of tissue aging and damage. Macrophage dysfunction plays an important role in immunosenescence. Microglial dysfunction has been linked to age-dependent neurodegenerations. Retinal pigment epithelial (RPE) cell dysfunction has been implicated in the pathogenesis of age-related macular degeneration (AMD). Despite several reports on the characterization of aged phagocytes, the role of phagocyte dysfunction in tissue aging and degeneration is yet to be fully appreciated. Lack of knowledge of molecular mechanisms by which aging reduces phagocyte function has hindered our capability to exploit the therapeutic potentials of phagocytosis for prevention or delay of tissue degeneration. This review summarizes our current knowledge of phagocyte dysfunction in aged tissues and discusses possible links to age-related diseases. We highlight the challenges to decipher the molecular mechanisms, present new research approaches and envisage future strategies to prevent phagocyte dysfunction, tissue aging and degeneration.
Bonilla M, Martin-Morales N, Galvez-Rueda R, Raya-Alvarez E, Mesa F J Clin Med. 2024; 13(22).
PMID: 39597974 PMC: 11594594. DOI: 10.3390/jcm13226831.
Li C, Xu W, Li L, Zhou Y, Yao G, Chen G Adv Sci (Weinh). 2024; 11(48):e2408044.
PMID: 39455287 PMC: 11672322. DOI: 10.1002/advs.202408044.
Influence of the spaceflight environment on macrophage lineages.
An R, Blackwell V, Harandi B, Gibbons A, Siu O, Irby I NPJ Microgravity. 2024; 10(1):63.
PMID: 38862517 PMC: 11166655. DOI: 10.1038/s41526-023-00293-0.
The immunobiology of herpes simplex virus encephalitis and post-viral autoimmunity.
Cleaver J, Jeffery K, Klenerman P, Lim M, Handunnetthi L, Irani S Brain. 2023; 147(4):1130-1148.
PMID: 38092513 PMC: 10994539. DOI: 10.1093/brain/awad419.
The impact of early RPE cell junction loss on VEGF, Ang-2, and TIMP secretion in vitro.
Paterson C, Cannon J, Vargis E Mol Vis. 2023; 29:87-101.
PMID: 37859808 PMC: 10584031.