title: Cells derived from young bone marrow alleviate renal aging.
abstract: Bone marrow-derived stem cells may modulate renal injury, but the effects may depend on the age of the stem cells. Here we investigated whether bone marrow from young mice attenuates renal aging in old mice. We radiated female 12-mo-old 129SvJ mice and reconstituted them with bone marrow cells (BMC) from either 8-wk-old (young-to-old) or 12-mo-old (old-to-old) male mice. Transfer of young BMC resulted in markedly decreased deposition of collagen IV in the mesangium and less β-galactosidase staining, an indicator of cell senescence. These changes paralleled reduced expression of plasminogen activator inhibitor-1 (PAI-1), PDGF-B (PDGF-B), the transdifferentiation marker fibroblast-specific protein-1 (FSP-1), and senescence-associated p16 and p21. Tubulointerstitial and glomerular cells derived from the transplanted BMC did not show β-galactosidase activity, but after 6 mo, there were more FSP-1-expressing bone marrow-derived cells in old-to-old mice compared with young-to-old mice. Young-to-old mice also exhibited higher expression of the anti-aging gene Klotho and less phosphorylation of IGF-1 receptor β. Taken together, these data suggest that young bone marrow-derived cells can alleviate renal aging in old mice. Direct parenchymal reconstitution by stem cells, paracrine effects from adjacent cells, and circulating anti-aging molecules may mediate the aging of the kidney.
authors.affiliation: Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Hai-Chun
authors.initials: HC
authors.lastname: Yang
authors.forename: Michele
authors.initials: M
authors.lastname: Rossini
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Ma
authors.forename: Yiqin
authors.initials: Y
authors.lastname: Zuo
authors.forename: Ji
authors.initials: J
authors.lastname: Ma
authors.forename: Agnes B
authors.initials: AB
authors.lastname: Fogo
mesh_terms: D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D005355:Fibrosis; D015870:Gene Expression / Q000502:physiology; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000473:pathology* / Q000502:physiology*; D000090265:Klotho Proteins; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D010641:Phenotype; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics; D012060:Rejuvenation / Q000502:physiology*; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000235:genetics; D058258:Serpin E2 / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000235:genetics
chemical_list: D020574:Proto-Oncogene Proteins c-sis; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse; D058258:Serpin E2; C511869:Serpine2 protein, mouse; D053773:Transforming Growth Factor beta1; D005966:Glucuronidase; D000090265:Klotho Proteins