Age-related myelin degradation burdens the clearance function of microglia during aging.
Myelin is synthesized as a multilamellar membrane, but the mechanisms of membrane turnover are unknown. We found that myelin pieces were gradually released from aging myelin sheaths and were subsequently cleared by microglia. Myelin fragmentation increased with age and led to the formation of insoluble, lipofuscin-like lysosomal inclusions in microglia. Thus, age-related myelin fragmentation is substantial, leading to lysosomal storage and contributing to microglial senescence and immune dysfunction in aging.
Max Planck Institute of Experimental Medicine, Göttingen, Germany.
Shima
S
Safaiyan
Department of Psychiatry, Ludwig-Maximillian University, Munich, Germany.
Nirmal
N
Kannaiyan
Max Planck Institute of Experimental Medicine, Göttingen, Germany.|Institute of Neuronal Cell Biology, Technical University Munich, Munich, Germany.
Nicolas
N
Snaidero
Department of Psychiatry and Psychotherapy, Freiburg, Germany.
Simone
S
Brioschi
Department of Psychiatry and Psychotherapy, Freiburg, Germany.|Department of Neuroscience, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Knut
K
Biber
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Simon
S
Yona
Department of Developmental and Cell Biology, University of California, Irvine, Irvine, California, USA.
Aimee L
AL
Edinger
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Steffen
S
Jung
Max Planck Institute of Experimental Medicine, Göttingen, Germany.|Department of Psychiatry, Ludwig-Maximillian University, Munich, Germany.
Moritz J
MJ
Rossner
Max Planck Institute of Experimental Medicine, Göttingen, Germany.|Institute of Neuronal Cell Biology, Technical University Munich, Munich, Germany.|German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.|Munich Cluster of Systems Neurology (SyNergy), Munich, Germany.
Mikael
M
Simons
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000378:metabolism; D008062:Lipofuscin / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism*
D008062:Lipofuscin