CRON and 'pha-4'

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Al Pater <old542000@...> wrote: Date: Wed, 2 May 2007 15:32:27 -0700 (PDT)From: Al Pater <old542000@...>Subject: Re: [ ] CRON and 'pha-4' Hi All,It seems that one of the the http://en.wikipedia.org/wiki/Forkhead_box_proteins called FOXA1 has a http://www.cbil.upenn.edu/RAD/php/displayStudy.php?study_id=1030 role in pancreas function.The below paper is pdf-availed. Notes:"The role of PHA-4 in lifespan determination is specific for dietary restriction, because it is not required for the increased longevity caused by other genetic pathways that regulate ageing.""PHA-4 is orthologous to

the human Foxa family of transcription factors (Supplementary Fig. 2)16. Foxa1 homozygous mutant mice die shortly after birth, do not gain weight and are hypoglycaemic, suggesting an important role for Foxa1 in pancreatic cell function and a central role in metabolic homeostasis17, 18. Foxa2 is also required for glucagon expression in the pancreas and induction of gluconeogenic genes during fasting in the liver19. Foxa3 mutant mice become hypoglycaemic after a prolonged fasting20, 21."PHA-4/Foxa mediates diet-restriction-induced longevity of C. elegansSiler H. Panowski, Suzanne Wolff, Hugo Aguilaniu, Jenni Durieux & DillinNature advance online publication 2 May 2007Reduced food intake as a result of dietary restriction increases the lifespan of a wide variety of metazoans and delays the onset of multiple age-related pathologies. Dietary restriction elicits a genetically programmed response to nutrient availability that cannot be

explained by a simple reduction in metabolism or slower growth of the organism. In the nematode worm Caenorhabditis elegans, the transcription factor PHA-4 has an essential role in the embryonic development of the foregut and is orthologous to genes encoding the mammalian family of Foxa transcription factors, Foxa1, Foxa2 and Foxa3. Foxa family members have important roles during development, but also act later in life to regulate glucagon production and glucose homeostasis, particularly in response to fasting. Here we describe a newly discovered, adult-specific function for PHA-4 in the regulation of diet-restriction-mediated longevity in C. elegans. The role of PHA-4 in lifespan determination is specific for dietary restriction, because it is not required for the increased longevity caused by other genetic pathways that regulate ageing.Rodney <perspect1111@...> wrote: http://news.bbc.co.uk/2/hi/science/nature/6612411.stmRodney.-- Al Pater, PhD; email: Alpater@... Ahhh...imagining that irresistible "new car" smell?Check out new cars at Autos. -- Al Pater, PhD; email: Alpater@...

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