Answer the following questions in regards to the paper “Sirtuins, epigenetics and longevity.”

1. Briefly, without re-wrting the paper, describe how yeast and mammalian sirtuins are conserved across the divergent species.
2. Choose one surtuin that is conserved between yeast and mammals and describe in detail its mechanism of action and how that effects longevity.
3. How does calorie restriction affect DNA methylation leading to an increase in longevity?
4. Descriibe briefly the general function of micro RNAs.
5. Using your own words, describe the role of miR-34, SIRT1 and p53 in aging.
6. In your own words, what are the overall conclusions of the paper?

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1. Briefly, without re-writing the paper, describe how yeast and mammalian sirtuins are conserved across the divergent species.
The sirtuins, NAD-dependent protein deacetylases, are broadly conserved from yeast to human. In yeast, C. elegans and D. melanogaster most studied protein is Sir2, and in mammals there are seven sirtuins (SIRT1-7). Although they have different substrate affinity and subcellular localization, they all share a similar catalytic core domain and use NAD+ as a co-substrate. They are involved in the cell metabolism and can prevent telomere shortening, inflammation and aging. Sirtuins prevent DNA damage by suppressing ROS production, activating PARP and facilitating DNA double-strand breaks through homologous recombination. The epigenetic mechanisms which activate sirtuins and their deacetylase, deacylase and O-ADP-ribosylase activity on histone modifications are conserved across the species. Yeast Sir2 and mammals SIRT1 and SIRT6 are activated by calorie restriction which affects longevity. In aging, sirtuins expression is downregulated by miRNAs and p53....

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