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Comparative Study
. 2011 Mar 15;10(6):904-11.
doi: 10.4161/cc.10.6.14912. Epub 2011 Mar 15.

Comparative transcriptional pathway bioinformatic analysis of dietary restriction, Sir2, p53 and resveratrol life span extension in Drosophila

Michael Antosh  1 , Rachel Whitaker, Adam Kroll, Suzanne Hosier, Chengyi Chang, Johannes Bauer, Leon Cooper, Nicola Neretti, Stephen L Helfand
Affiliations
Comparative Study

Comparative transcriptional pathway bioinformatic analysis of dietary restriction, Sir2, p53 and resveratrol life span extension in Drosophila

Michael Antosh et al. Cell Cycle. .

Abstract

A multiple comparison approach using whole genome transcriptional arrays was used to identify genes and pathways involved in calorie restriction/dietary restriction (DR) life span extension in Drosophila. Starting with a gene centric analysis comparing the changes in common between DR and two DR related molecular genetic life span extending manipulations, Sir2 and p53, lead to a molecular confirmation of Sir2 and p53's similarity with DR and the identification of a small set of commonly regulated genes. One of the identified upregulated genes, takeout, known to be involved in feeding and starvation behavior, and to have sequence homology with Juvenile Hormone (JH) binding protein, was shown to directly extend life span when specifically overexpressed. Here we show that a pathway centric approach can be used to identify shared physiological pathways between DR and Sir2, p53 and resveratrol life span extending interventions. The set of physiological pathways in common among these life span extending interventions provides an initial step toward defining molecular genetic and physiological changes important in life span extension. The large overlap in shared pathways between DR, Sir2, p53 and resveratrol provide strong molecular evidence supporting the genetic studies linking these specific life span extending interventions.

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Figures

Figure 1
Figure 1
DR is a highly pleiotropic process that influences a variety of biological processes, including physiology, fertility, behavior and life span. While the nature of most of these pathways remains unknown, a molecular framework for at least some aspects of DR-dependent life span regulation can be constructed. Under DR conditions (red), rpd3 is down and dSir2 is upregulated. dSir2 activity inhibits Dmp53 (amongst other targets), leading to a portion of the DR related life span extension seen. DR life span extension is larger than life span extension of rpd3, dSir2 or Dmp53 manipulation. Thus each of these interventions define only a portion of the DR life span extension. Reviewed from reference .
Figure 2
Figure 2
Heat map of KEGG gene sets from Sir2 and p53 long-lived flies show similarity with a DR signature gene set. Red are gene sets that are statistically significantly upregulated, blue are gene sets that are statistically significantly downregulated and black are gene sets that are not statistically significantly changed. RNA is from 10-day old whole body of females. Sir2 are flies expressing Sir2 in adult neurons and p53 are flies expressing DN-Dmp53 in adult neurons. yw, w1118 DR flies are genetically identical to Sir2 flies, but without RU486 and genetically very similar to the DN-Dmp53 flies. KEGG categories and scores are in Supplemental Table 2.
Figure 3
Figure 3
Heat map of KEGG gene sets from DR of female whole body and female head and thorax appear very different. Red are gene sets that are statistically significantly upregulated, blue are gene sets that are statistically significantly downregulated and black are gene sets that are not statistically significantly changed. RNA is from Canton-S (C-S) DR and high calorie fed 10-day old female whole bodies or only heads and thoraces. KEGG categories and scores are in Supplemental Table 3.
Figure 4
Figure 4
Heat map of KEGG gene sets from DR and resveratrol female head and thorax appear very similar. Red are gene sets that are statistically significantly upregulated, blue are gene sets that are statistically significantly downregulated and black are gene sets that are not statistically significantly changed. RNA is from the same cohort of Canton-S (C-S) 10-day old female heads and thoraces on a DR diet, high calorie food or fed resveratrol. KEGG categories and scores are in Supplemental Table 4.
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References

    1. Wanagat J, Allison DB, Weindruch R. Caloric intake and aging: mechanisms in rodents and a study in nonhuman primates. Toxicol Sci. 1999;52:35–40. - PubMed
    1. Weindruch R. The retardation of aging by caloric restriction: studies in rodents and primates. Toxicol Pathol. 1996;24:742–745. - PubMed
    1. Kayo T, Allison DB, Weindruch R, Prolla TA. Influences of aging and caloric restriction on the transcriptional profile of skeletal muscle from rhesus monkeys. Proc Natl Acad Sci USA. 2001;98:5093–5098. - PMC - PubMed
    1. Lane MA, Mattison J, Ingram DK, Roth GS. Caloric restriction and aging in primates: Relevance to humans and possible CR mimetics. Microsc Res Tech. 2002;59:335–338. - PubMed
    1. Chapman T, Partridge L. Female fitness in Drosophila melanogaster: an interaction between the effect of nutrition and of encounter rate with males. Proc R Soc Lond B Biol Sci. 1996;263:755–759. - PubMed

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