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Extracellular Nicotinamide Phosphoribosyltransferase Is a Component of the Senescence-Associated Secretory Phenotype.
Kuehnemann, Chisaka; Hu, Kang-Quan; Butera, Kayla; Patel, Sandip K; Bons, Joanna; Schilling, Birgit; Aguayo-Mazzucato, Cristina; Wiley, Christopher D.
Afiliación
  • Kuehnemann C; Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, United States.
  • Hu KQ; Buck Institute for Research on Aging, Novato, CA, United States.
  • Butera K; Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, United States.
  • Patel SK; Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, United States.
  • Bons J; Buck Institute for Research on Aging, Novato, CA, United States.
  • Schilling B; Buck Institute for Research on Aging, Novato, CA, United States.
  • Aguayo-Mazzucato C; Buck Institute for Research on Aging, Novato, CA, United States.
  • Wiley CD; Joslin Diabetes Center, Harvard Medical School, Boston, MA, United States.
Front Endocrinol (Lausanne) ; 13: 935106, 2022.
Article en En | MEDLINE | ID: mdl-35909566
Cellular senescence is a stress or damage response by which a cell adopts of state of essentially permanent proliferative arrest, coupled to the secretion of a number of biologically active molecules. This senescence-associated secretory phenotype (SASP) underlies many of the degenerative and regenerative aspects of cellular senescence - including promoting wound healing and development, but also driving diabetes and multiple age-associated diseases. We find that nicotinamide phosphoribosyltransferase (NAMPT), which catalyzes the rate-limiting step in nicotinamide adenine dinucleotide (NAD) biosynthesis, is elevated in senescent cells without a commensurate increase in NAD levels. This elevation is distinct from the acute DNA damage response, in which NAD is depleted, and recovery of NAD by NAMPT elevation is AMPK-activated protein kinase (AMPK)-dependent. Instead, we find that senescent cells release extracellular NAMPT (eNAMPT) as part of the SASP. eNAMPT has been reported to be released as a catalytically active extracellular vesicle-contained dimer that promotes NAD increases in other cells and extends lifespan, and also as free monomer that acts as a damage-associated molecular pattern and promotes conditions such as diabetes and fibrosis. Senescent cells released eNAMPT as dimer, but surprisingly eNAMPT appeared in the soluble secretome while being depleted from exosomes. Finally, diabetic mice showed elevated levels of eNAMPT, and this was lowered by treatment with the senolytic drug, ABT-263. Together, these data reveal a new SASP factor with implications for NAD metabolism.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Citocinas / Diabetes Mellitus Experimental / Nicotinamida Fosforribosiltransferasa / Fenotipo Secretor Asociado a la Senescencia Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: Front Endocrinol (Lausanne) Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Citocinas / Diabetes Mellitus Experimental / Nicotinamida Fosforribosiltransferasa / Fenotipo Secretor Asociado a la Senescencia Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: Front Endocrinol (Lausanne) Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza