Aging networks in Caenorhabditis elegans: AMP-activated protein kinase (aak-2) links multiple aging and metabolism pathways.
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.
Curtis
Rory
R
Elixir Pharmaceuticals, One Kendall Square, Building 1000, Cambridge, MA 02139, USA.
O'Connor
Greg
G
DiStefano
Peter S
PS
D055372:AMP-Activated Protein Kinases; D000227:Adenine Nucleotides / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000254:growth & development / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D005247:Feeding Behavior; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental; D018095:Germ-Line Mutation / Q000235:genetics; D007814:Larva / Q000254:growth & development; D008136:Longevity; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000378:metabolism*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D037761:Sirtuins / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
D000227:Adenine Nucleotides; D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D009097:Multienzyme Complexes; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D017346:Protein Serine-Threonine Kinases; C510541:AAK-2 protein, C elegans; D055372:AMP-Activated Protein Kinases; C507014:SIR-2.1 protein, C elegans; D037761:Sirtuins