title: Overcoming the aging systemic milieu to restore neural stem cell function.
abstract: As mammals age, the rate of neurogenesis in the brain declines with a concomitant reduction in cognitive ability. Recent data suggest that plasma-borne factors are responsible for inhibition of neurogenesis. When the circulatory systems of old and young mice are connected, the old mice experience increased neurogenesis and the young mice exhibit less neurogenesis, suggesting the importance of systemic circulating factors. Chemokine CCL11/eotaxin has been identified as a factor that increases with aging. Injections of CCL11 inhibit neurogenesis in young mice, an effect likely mediated by CCR3 receptors on neural stem cells. Identification of a specific factor that plays a causative role in stem cell dysfunction in aging is consistent with data showing that transforming growth factor-β (TGF-β) inhibits satellite cell-mediated repair. Together, these data suggest that the systemic milieu plays a critical role in the aging of adult stem cells. Because adult stem cells help maintain homeostasis by providing the possibility of replacing metabolically damaged differentiated cells, aging of the systemic milieu and stem cell niches may drive functional decline during aging. The identification of a specific systemic change suggests that aging is more amenable to therapeutic modulation than work on global metabolism-derived damage and cellular senescence implies.
authors.affiliation: Panorama Research Institute, 1230 Bordeaux DriveSunnyvale, CA 94089, USA. amend@regensci.org
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Mendelsohn
authors.forename: James W
authors.initials: JW
authors.lastname: Larrick
mesh_terms: D000375:Aging; D000818:Animals; D001921:Brain / Q000378:metabolism; D016922:Cellular Senescence; D054413:Chemokine CCL11 / Q000378:metabolism; D003071:Cognition; D007107:Immune System; D008568:Memory; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology*; D055495:Neurogenesis; D054397:Receptors, CCR3 / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C515457:Ccl11 protein, mouse; C515351:Ccr3 protein, mouse; D054413:Chemokine CCL11; D054397:Receptors, CCR3; D016212:Transforming Growth Factor beta