Genomica nutrizionale e approccio sperimentale Go et al., 2003.

Presentazione sul tema: "Genomica nutrizionale e approccio sperimentale Go et al., 2003."— Transcript della presentazione:

1 Genomica nutrizionale e approccio sperimentale Go et al., 2003

2 La metilazione dei dinucleotidi 5’CpG3’ nei promotori modula l’espressione dei geni

3 Mantenimento del pattern di metilazione durante la duplicazione del DNA

4 L’acetilazione degli istoni

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6 Nutrienti, attività genica e tumore

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9 Ross et al., 2003

10 Componenti nutrizionali bio-attivi Cancer prevention – the potential for diet to modulate molecular signalling Trends in Molecular Medicine, Manson, 2002

11 Manson, 2002

12 Depending on the circumstances, dietary compounds such as curcumin, epigallocatechin gallate (EGCG), resveratrol and indole-3-carbinol (I3C) can up- or down-regulate signalling to induce stress-response genes, or growth arrest and apoptosis Manson, 2002

13 Different chemopreventive agents can suppress the activity of IKK, PI3K and/or PKB, inhibit the translocation of NF-kB to the nucleus, or upregulate PTEN Manson, 2002

14 Chemopreventive agents, such as indole-3-carbinol and epigallocatechin gallate, can downregulate the expression or activity of CDKs and cyclins, and upregulate CDK inhibitors such as p21 and p27, thereby causing cell-cycle arrest in G1. Manson, 2002

15 Induction of stress-response genes by chemopreventive chemicals Manson, 2002

16 Restrizione calorica Regime dietetico a basso contenuto calorico in assenza di sottonutrizione o malnutrizione Allungamento della sopravvivenza del 50% in lievito, nematodi, roditori e scimmie

17 Mattson, 2003

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20 Koubova et al., 2003

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22 Pathways metabolici modificati dalla restrizione calorica Koubova et al., 2003

23 Hyon Jeen Kim et al., 2002 Restrizione calorica e stress ossidativo

24 Possibile meccanismo attraverso cui la CR migliora la funzionalità neuronale

25 Restrizione calorica e invecchiamento Barja, 2002

26 CR manipulates the membrane fatty acid components as an adaptive measure against age- related peroxidizability — an efficient and smart strategy to resist oxidative stress. Barja, 2002

27 Shelke et al., 2003

28 Suppression of microsomal production of reactive oxygen species by CR. AS, ad libitum- fed, sedentary; AE, ad libitum-fed, exercising; RS, CR, sedentary; RE, CR, exercising; DCF = 2'7'-dichlorodihydrofluorescin Exercised CR animals are shown to have an additional extended mean life span of  10% beyond their nonexercised CR counterparts. Yu et al., 2003

29 ARC (apoptosis repressor) levels in the brain of adult (12AD), old (26AD), and old caloric restricted (26CR) Fischer 344 male rats determined by Western blot analysis

30 Reduction of the incidence of tumors following reduction of food intake An even more remarkable example of CR’s ability to resist irradiation is shown in the work of Gross and Dreyfuss, who challenged mice with gamma irradiation to induce tumorigenesis. They not only show a clear-cut tumor suppression by CR (TABLE) but also that CR rats had a far better capability of resisting one of the most deleterious forms of stressors. Shelke et al., 2003

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32 Lee et al., 1999