#8 NS 160 Sirtuins - Sirtuins - Metabolic Regulation &...

Info iconThis preview shows pages 1–9. Sign up to view the full content.

View Full Document Right Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: Sirtuins - Metabolic Regulation & Longevity Caloric Restriction Caloric restriction (CR), normally defned as a 20-40% reduction in caloric intake without malnutrition, extends the longevity in yeast, spiders, worms, Fies, fsh, mice, rats and rhesus monkeys CR protects rom many aging associated pathophysiologies including type-2 diabetes, atherosclerosis, oxidative damage and senescence o the immune system CR and Longevity - Why & How Live extension due to CR may represent adaptation to scarcity. Slowing down aging and reproduction during scarcity maximizes chances of survival and reproduction when food is available again. CR affects many metabolic pathways. Mammalian signaling pathways involved in CR effect on aging are not completely understood but include insulin signaling, AMPK activation and Sirtuins CR and Longevity - Why & How Live extension due to CR may represent adaptation to scarcity. Slowing down aging and reproduction during scarcity maximizes chances of survival and reproduction when food is available again. CR affects many metabolic pathways. Mammalian signaling pathways involved in CR effect on aging are not completely understood but include insulin signaling, AMPK activation and Sirtuins Sirtuins are mediators of CR The yeast protein Sir2 (silent information regulator 2) was isolated in a screen for silencing factors of the mating locus and later found to extend lifespan in S. cerevisiae. Humans express 7 Sir2 homologs (sirtuins SIRT1-7) that differ in their subcellular localization. CR enhances sirtuin expression and CR dependent lifespan extension in sirtuin- deFcient yeast and mice is abolished. Sirtuins are mediators of CR The yeast protein Sir2 (silent information regulator 2) was isolated in a screen for silencing factors of the mating locus and later found to extend lifespan in S. cerevisiae. Humans express 7 Sir2 homologs (sirtuins SIRT1-7) that differ in their subcellular localization. CR enhances sirtuin expression and CR dependent lifespan extension in sirtuin- deFcient yeast and mice is abolished. Sirtuins and Nutrient Sensing Sirtuins are NAD +-dependent protein deacetylases. CR may activate sirtuins by changing the redox balance between NADH and NAD + . Alternatively, CR may decrease nicotinamide (a product and inhibitor of SIRT1 catalytic activity). In mammalian cells Nampt (NAM phosphoribosyltransferase) is the rate- limiting enzyme of the NAM -> NAD+ resynthesis pathway and regulation of Nampt activity by CR can lead to SIRT1 activation Sirtuins and Nutrient Sensing Sirtuins are NAD +-dependent protein deacetylases. CR may activate sirtuins by changing the redox balance between NADH and NAD + ....
View Full Document

This document was uploaded on 02/21/2010.

Page1 / 29

#8 NS 160 Sirtuins - Sirtuins - Metabolic Regulation &...

This preview shows document pages 1 - 9. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online