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SIRT3 reverses aging-associated degeneration.
Brown, Katharine; Xie, Stephanie; Qiu, Xiaolei; Mohrin, Mary; Shin, Jiyung; Liu, Yufei; Zhang, Dan; Scadden, David T; Chen, Danica.
Afiliação
  • Brown K; Program in Metabolic Biology, Nutritional Sciences & Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
Cell Rep ; 3(2): 319-27, 2013 Feb 21.
Article em En | MEDLINE | ID: mdl-23375372
ABSTRACT
Despite recent controversy about their function in some organisms, sirtuins are thought to play evolutionarily conserved roles in lifespan extension. Whether sirtuins can reverse aging-associated degeneration is unknown. Tissue-specific stem cells persist throughout the entire lifespan to repair and maintain tissues, but their self-renewal and differentiation potential become dysregulated with aging. We show that SIRT3, a mammalian sirtuin that regulates the global acetylation landscape of mitochondrial proteins and reduces oxidative stress, is highly enriched in hematopoietic stem cells (HSCs) where it regulates a stress response. SIRT3 is dispensable for HSC maintenance and tissue homeostasis at a young age under homeostatic conditions but is essential under stress or at an old age. Importantly, SIRT3 is suppressed with aging, and SIRT3 upregulation in aged HSCs improves their regenerative capacity. Our study illuminates the plasticity of mitochondrial homeostasis controlling stem cell and tissue maintenance during the aging process and shows that aging-associated degeneration can be reversed by a sirtuin.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Senescência Celular / Sirtuína 3 Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Revista: Cell Rep Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Senescência Celular / Sirtuína 3 Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Revista: Cell Rep Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Estados Unidos