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An aged immune system drives senescence and ageing of solid organs.
Yousefzadeh, Matthew J; Flores, Rafael R; Zhu, Yi; Schmiechen, Zoe C; Brooks, Robert W; Trussoni, Christy E; Cui, Yuxiang; Angelini, Luise; Lee, Kyoo-A; McGowan, Sara J; Burrack, Adam L; Wang, Dong; Dong, Qing; Lu, Aiping; Sano, Tokio; O'Kelly, Ryan D; McGuckian, Collin A; Kato, Jonathan I; Bank, Michael P; Wade, Erin A; Pillai, Smitha P S; Klug, Jenna; Ladiges, Warren C; Burd, Christin E; Lewis, Sara E; LaRusso, Nicholas F; Vo, Nam V; Wang, Yinsheng; Kelley, Eric E; Huard, Johnny; Stromnes, Ingunn M; Robbins, Paul D; Niedernhofer, Laura J.
Afiliação
  • Yousefzadeh MJ; Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, USA.
  • Flores RR; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
  • Zhu Y; Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, USA.
  • Schmiechen ZC; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
  • Brooks RW; Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
  • Trussoni CE; Center for Immunology, University of Minnesota Medical School, Minneapolis, MN, USA.
  • Cui Y; Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL, USA.
  • Angelini L; Division of Gastroenterology, Center for Cell Signaling in Gastroenterology, Mayo Clinic, Rochester, MN, USA.
  • Lee KA; Department of Chemistry, University of California Riverside, Riverside, CA, USA.
  • McGowan SJ; Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, USA.
  • Burrack AL; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
  • Wang D; Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, USA.
  • Dong Q; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
  • Lu A; Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, USA.
  • Sano T; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
  • O'Kelly RD; Center for Immunology, University of Minnesota Medical School, Minneapolis, MN, USA.
  • McGuckian CA; Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
  • Kato JI; Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
  • Bank MP; Department of Orthopedic Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
  • Wade EA; Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL, USA.
  • Pillai SPS; Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, USA.
  • Klug J; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
  • Ladiges WC; Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, USA.
  • Burd CE; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
  • Lewis SE; Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL, USA.
  • LaRusso NF; Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL, USA.
  • Vo NV; Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL, USA.
  • Wang Y; Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Kelley EE; Department of Comparative Medicine, University of Washington, Seattle, WA, USA.
  • Huard J; Department of Comparative Medicine, University of Washington, Seattle, WA, USA.
  • Stromnes IM; Departments of Molecular Genetics and Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA.
  • Robbins PD; Department of Physiology & Pharmacology, West Virginia University, Morgantown, WV, USA.
  • Niedernhofer LJ; Division of Gastroenterology, Center for Cell Signaling in Gastroenterology, Mayo Clinic, Rochester, MN, USA.
Nature ; 594(7861): 100-105, 2021 06.
Article em En | MEDLINE | ID: mdl-33981041
ABSTRACT
Ageing of the immune system, or immunosenescence, contributes to the morbidity and mortality of the elderly1,2. To define the contribution of immune system ageing to organism ageing, here we selectively deleted Ercc1, which encodes a crucial DNA repair protein3,4, in mouse haematopoietic cells to increase the burden of endogenous DNA damage and thereby senescence5-7 in the immune system only. We show that Vav-iCre+/-;Ercc1-/fl mice were healthy into adulthood, then displayed premature onset of immunosenescence characterized by attrition and senescence of specific immune cell populations and impaired immune function, similar to changes that occur during ageing in wild-type mice8-10. Notably, non-lymphoid organs also showed increased senescence and damage, which suggests that senescent, aged immune cells can promote systemic ageing. The transplantation of splenocytes from Vav-iCre+/-;Ercc1-/fl or aged wild-type mice into young mice induced senescence in trans, whereas the transplantation of young immune cells attenuated senescence. The treatment of Vav-iCre+/-;Ercc1-/fl mice with rapamycin reduced markers of senescence in immune cells and improved immune function11,12. These data demonstrate that an aged, senescent immune system has a causal role in driving systemic ageing and therefore represents a key therapeutic target to extend healthy ageing.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Especificidade de Órgãos / Envelhecimento / Imunossenescência / Sistema Imunitário Limite: Animals Idioma: En Revista: Nature Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Especificidade de Órgãos / Envelhecimento / Imunossenescência / Sistema Imunitário Limite: Animals Idioma: En Revista: Nature Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos