Microglia-aging: roles of microglial lysosome- and mitochondria-derived reactive oxygen species in brain aging.
The accumulation of lysosome- and mitochondria-derived reactive oxygen species (ROS) are the most important causative factors for aging. Autophagic dysfunction and mitochondrial DNA damage in the central nervous system (CNS) are prominently found in microglia, the resident mononuclear phagocyte population within the CNS. The autophagic dysfunction may induce the defective turnover of mitochondria, which results in the accumulation of ROS-hypergenerating older mitochondria in microglia. ROS activate redox-dependent transduction cascades and transcription factors, including nuclear factor-kappaB, which induce the expression of inflammatory genes. Therefore, "microglia-aging" could function as a major driver for brain aging. Furthermore, the prevention of lysosomal autophagic dysfunction and mitochondrial DNA damage in microglia may therefore be a potentially effective new pharmaceutical intervention against brain aging.
Nakanishi
Hiroshi
H
Laboratory of Oral Aging Science, Faculty of Dental Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan. nakan@dent.kyushu-u.ac.jp
Wu
Zhou
Z
D000375:Aging; D000818:Animals; D001343:Autophagy / Q000502:physiology; D001921:Brain / Q000502:physiology*; D002402:Cathepsin D / Q000378:metabolism; D002403:Cathepsins / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D008062:Lipofuscin / Q000378:metabolism; D008247:Lysosomes / Q000502:physiology*; D017628:Microglia / Q000166:cytology / Q000502:physiology*; D008928:Mitochondria / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000378:metabolism; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D008959:Models, Neurological; D009457:Neuroglia / Q000166:cytology / Q000502:physiology; D009474:Neurons / Q000502:physiology; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D008062:Lipofuscin; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D014157:Transcription Factors; C422562:mitochondrial transcription factor A; D002403:Cathepsins; D002402:Cathepsin D; C103607:mitochondrial ATPase subunit c; D025261:Mitochondrial Proton-Translocating ATPases