Genomica nutrizionale e approccio sperimentale Go et al., 2003

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

Mantenimento del pattern di metilazione durante la duplicazione del DNA

L’acetilazione degli istoni

Nutrienti, attività genica e tumore

Ross et al., 2003

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

Manson, 2002

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

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

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

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

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

Mattson, 2003

Koubova et al., 2003

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

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

Possibile meccanismo attraverso cui la CR migliora la funzionalità neuronale

Restrizione calorica e invecchiamento Barja, 2002

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

Shelke et al., 2003

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

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

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

Lee et al., 1999