TY - JOUR
T1 - Targeting Efferocytosis in Inflammaging
AU - Poon, Ivan K.H.
AU - Ravichandran, Kodi S.
N1 - Publisher Copyright:
Copyright © 2024 by the author(s).
PY - 2024/1/23
Y1 - 2024/1/23
N2 - Rapid removal of apoptotic cells by phagocytes, a process known as efferocytosis, is key for the maintenance of tissue homeostasis, the resolution of inflammation, and tissue repair. However, impaired efferocytosis can result in the accumulation of apoptotic cells, subsequently triggering sterile inflammation through the release of endogenous factors such as DNA and nuclear proteins from membrane permeabilized dying cells. Here, we review the molecular basis of the three key phases of efferocytosis, that is, the detection, uptake, and degradation of apoptotic materials by phagocytes. We also discuss how defects in efferocytosis due to the alteration of phagocytes and dying cells can contribute to the low-grade chronic inflammation that occurs during aging, described as inflammaging. Lastly, we explore opportunities in targeting and harnessing the efferocytic machinery to limit aging-associated inflammatory diseases.
AB - Rapid removal of apoptotic cells by phagocytes, a process known as efferocytosis, is key for the maintenance of tissue homeostasis, the resolution of inflammation, and tissue repair. However, impaired efferocytosis can result in the accumulation of apoptotic cells, subsequently triggering sterile inflammation through the release of endogenous factors such as DNA and nuclear proteins from membrane permeabilized dying cells. Here, we review the molecular basis of the three key phases of efferocytosis, that is, the detection, uptake, and degradation of apoptotic materials by phagocytes. We also discuss how defects in efferocytosis due to the alteration of phagocytes and dying cells can contribute to the low-grade chronic inflammation that occurs during aging, described as inflammaging. Lastly, we explore opportunities in targeting and harnessing the efferocytic machinery to limit aging-associated inflammatory diseases.
KW - aging
KW - apoptosis
KW - cell clearance
KW - cell death
KW - efferocytosis
KW - inflammaging
UR - http://www.scopus.com/inward/record.url?scp=85183312180&partnerID=8YFLogxK
U2 - 10.1146/annurev-pharmtox-032723-110507
DO - 10.1146/annurev-pharmtox-032723-110507
M3 - Review article
C2 - 37585658
AN - SCOPUS:85183312180
SN - 0362-1642
VL - 64
SP - 339
EP - 357
JO - Annual Review of Pharmacology and Toxicology
JF - Annual Review of Pharmacology and Toxicology
ER -