title: Aging neural progenitor cells have decreased mitochondrial content and lower oxidative metabolism.
abstract: Although neurogenesis occurs in discrete areas of the adult mammalian brain, neural progenitor cells (NPCs) produce fewer new neurons with age. To characterize the molecular changes that occur during aging, we performed a proteomic comparison between primary-cultured NPCs from the young adult and aged mouse forebrain. This analysis yielded changes in proteins necessary for cellular metabolism. Mitochondrial quantity and oxygen consumption rates decrease with aging, although mitochondrial DNA in aged NPCs does not have increased mutation rates. In addition, aged cells are resistant to the mitochondrial inhibitor rotenone and proliferate in response to lowered oxygen conditions. These results demonstrate that aging NPCs display an altered metabolic phenotype, characterized by a coordinated shift in protein expression, subcellular structure, and metabolic physiology.
authors: Neurobiology and Behavior Program, University of Washington, Seattle, Washington 98109.
authors: Elizabeth A
authors: EA
authors: Stoll
authors: Department of Computer Science, University of Washington, Seattle, Washington 98109.
authors: Willy
authors: W
authors: Cheung
authors: Department of Neurological Surgery, University of Washington, Seattle, Washington 98109.
authors: Andrei M
authors: AM
authors: Mikheev
authors: Department of Medicine, University of Washington, Seattle, Washington 98109; Diabetes Endocrine Research Center, University of Washington, Seattle, Washington 98109.
authors: Ian R
authors: IR
authors: Sweet
authors: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington 98109; Department of Pathology, University of Washington, Seattle, Washington 98109.
authors: Jason H
authors: JH
authors: Bielas
authors: Department of Pathology, University of Washington, Seattle, Washington 98109.
authors: Jing
authors: J
authors: Zhang
authors: Department of Neurological Surgery, University of Washington, Seattle, Washington 98109.
authors: Robert C
authors: RC
authors: Rostomily
authors: Neurobiology and Behavior Program, University of Washington, Seattle, Washington 98109; Department of Neurological Surgery, University of Washington, Seattle, Washington 98109. Electronic address: phorner@uw.edu.
authors: Philip J
authors: PJ
authors: Horner
mesh_terms: D000375:Aging; D000818:Animals; D049109:Cell Proliferation; D005260:Female; D000860:Hypoxia; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal / Q000379:methods; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000473:pathology*; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption; D040901:Proteomics / Q000379:methods; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology*
chemical_list: D010100:Oxygen