TY - JOUR
T1 - Phagocyte dysfunction, tissue aging and degeneration
AU - Li, Wei
N1 - Funding Information:
I thank Dr. Duco Hamasaki for manuscript review. This work is partially supported by NIH R01GM094449 , R21HD075372 and grants from Florida James & Esther King Biomedical Research Program ( 1KF-38241 ), BrightFocus Foundation ( M2012026 ), Juvenile Diabetes Research Foundation ( 5-2012-189 ), Glaucoma Research Foundation and Florida Bankhead-Coley Cancer Research Program ( 2BF-04-46776 ).
PY - 2013/6
Y1 - 2013/6
N2 - 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.
AB - 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.
KW - Aging
KW - Macrophage
KW - Microglia
KW - Phagocyte dysfunction
KW - Phagocytosis
KW - Retinal pigment epithelium
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U2 - 10.1016/j.arr.2013.05.006
DO - 10.1016/j.arr.2013.05.006
M3 - Review article
C2 - 23748186
AN - SCOPUS:84888198684
VL - 12
SP - 1005
EP - 1012
JO - Ageing Research Reviews
JF - Ageing Research Reviews
SN - 1568-1637
IS - 4
ER -