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IL-6 can singlehandedly drive many features of frailty in mice.
Jergovic, Mladen; Thompson, Heather L; Bradshaw, Christine M; Sonar, Sandip Ashok; Ashgar, Arveen; Mohty, Niels; Joseph, Bellal; Fain, Mindy J; Cleveland, Kristan; Schnellman, Rick G; Nikolich-Zugich, Janko.
Afiliação
  • Jergovic M; Department of Immunobiology, University of Arizona College of Medicine-Tucson, Tucson, AZ, USA.
  • Thompson HL; University of Arizona Center on Aging, University of Arizona College of Medicine-Tucson, P.O.Box. 249221, 1501 N. Campbell Ave., Tucson, AZ, 85724, USA.
  • Bradshaw CM; Department of Immunobiology, University of Arizona College of Medicine-Tucson, Tucson, AZ, USA.
  • Sonar SA; University of Arizona Center on Aging, University of Arizona College of Medicine-Tucson, P.O.Box. 249221, 1501 N. Campbell Ave., Tucson, AZ, 85724, USA.
  • Ashgar A; Ventana-Roche Medical Systems, Oro Valley, AZ, USA.
  • Mohty N; Department of Immunobiology, University of Arizona College of Medicine-Tucson, Tucson, AZ, USA.
  • Joseph B; University of Arizona Center on Aging, University of Arizona College of Medicine-Tucson, P.O.Box. 249221, 1501 N. Campbell Ave., Tucson, AZ, 85724, USA.
  • Fain MJ; Department of Immunobiology, University of Arizona College of Medicine-Tucson, Tucson, AZ, USA.
  • Cleveland K; University of Arizona Center on Aging, University of Arizona College of Medicine-Tucson, P.O.Box. 249221, 1501 N. Campbell Ave., Tucson, AZ, 85724, USA.
  • Schnellman RG; Department of Immunobiology, University of Arizona College of Medicine-Tucson, Tucson, AZ, USA.
  • Nikolich-Zugich J; University of Arizona Center on Aging, University of Arizona College of Medicine-Tucson, P.O.Box. 249221, 1501 N. Campbell Ave., Tucson, AZ, 85724, USA.
Geroscience ; 43(2): 539-549, 2021 04.
Article em En | MEDLINE | ID: mdl-33629207
Frailty is a geriatric syndrome characterized by age-related declines in function and reserve resulting in increased vulnerability to stressors. The most consistent laboratory finding in frail subjects is elevation of serum IL-6, but it is unclear whether IL-6 is a causal driver of frailty. Here, we characterize a new mouse model of inducible IL-6 expression (IL-6TET-ON/+ mice) following administration of doxycycline (Dox) in food. In this model, IL-6 induction was Dox dose-dependent. The Dox dose that increased IL-6 levels to those observed in frail old mice directly led to an increase in frailty index, decrease in grip strength, and disrupted muscle mitochondrial homeostasis. Littermate mice lacking the knock-in construct failed to exhibit frailty after Dox feeding. Both naturally old mice and young Dox-induced IL-6TET-ON/+ mice exhibited increased IL-6 levels in sera and spleen homogenates but not in other tissues. Moreover, Dox-induced IL-6TET-ON/+ mice exhibited selective elevation in IL-6 but not in other cytokines. Finally, bone marrow chimera and splenectomy experiments demonstrated that non-hematopoietic cells are the key source of IL-6 in our model. We conclude that elevated IL-6 serum levels directly drive age-related frailty, possibly via mitochondrial mechanisms.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Envelhecimento / Interleucina-6 / Fragilidade Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Envelhecimento / Interleucina-6 / Fragilidade Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article