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Aging networks in Caenorhabditis elegans: AMP-activated protein kinase (aak-2) links multiple aging and metabolism pathways.
Curtis, Rory; O'Connor, Greg; DiStefano, Peter S.
Afiliación
  • Curtis R; Elixir Pharmaceuticals, One Kendall Square, Building 1000, Cambridge, MA 02139, USA.
Aging Cell ; 5(2): 119-26, 2006 Apr.
Article en En | MEDLINE | ID: mdl-16626391
Molecular genetics in lower organisms has allowed the elucidation of pathways that modulate the aging process. In certain instances, evolutionarily conserved genes and pathways have been shown to regulate lifespan in mammals as well. Many gene products known to affect lifespan are intimately involved in the control of energy metabolism, including the fuel sensor AMP-activated protein kinase (AMPK). We have shown previously that over-expression of an AMPK alpha subunit in Caenorhabditis elegans, designated aak-2, increases lifespan. Here we show the interaction of aak-2 with other pathways known to control aging in worms. Lifespan extension caused by daf-2/insulin-like signaling mutations was highly dependent on aak-2, as was the lifespan extension caused by over-expression of the deacetylase, sir-2.1. Similarly, there was partial requirement for aak-2 in lifespan extension by mitochondrial mutations (isp-1 and clk-1). Conversely, aak-2 was not required for lifespan extension in mutants lacking germline stem cells (glp-1) or mutants of the eating response (eat-2). These results show that aging is controlled by overlapping but distinct pathways and that AMPK/aak-2 represents a node in a network of evolutionarily conserved biochemical pathways that control aging.
Asunto(s)
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Envejecimiento / Proteínas Serina-Treonina Quinasas / Caenorhabditis elegans / Proteínas de Caenorhabditis elegans / Complejos Multienzimáticos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Aging Cell Año: 2006 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Envejecimiento / Proteínas Serina-Treonina Quinasas / Caenorhabditis elegans / Proteínas de Caenorhabditis elegans / Complejos Multienzimáticos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Aging Cell Año: 2006 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido