A natural compound Resveratrol (Rsv), which is found in high concentrations in grape skins and red wine, is expected to be a leading drug for elongating the life span and preventing oncogenesis. This compound is reported to have various beneficial effects on health, including the activation of complex I and anti-oxidative stress. We have been focusing on the regulation of the expression of human genes and have analyzed the promoter activities of several genes that encode DNA repair-functionassociated protein factors. Notably, the 5'-upstream regions of these genes very frequently contain the duplicated GGAA-motifs that allow HeLa S3 cells to respond to Rsv. In this review, we discuss the molecular mechanism by which Rsv regulates the expression of genes associated with DNA repair. We suggest the possibility of developing new anti-aging/cancer drugs without harmful side effects, based on a new concept of ameliorating or maintaining the cellular NAD + /NADH level.

Three Japanese individuals with homozygous delta zero-thalassemia from different families were the subjects of molecular genetic analysis. They were homozygous for seven polymorphic sites in the beta-globin gene cluster. Nucleotide sequence analysis of the delta-globin gene cloned from each patient revealed a single nucleotide substitution (T- C) 77 base pairs 5′ to the cap site, just upstream of the CCAAC box of the delta-globin gene. When introduced into COS cells, the gene was expressed at normal levels with proper processing of RNA. These results suggest that the complete suppression of delta-globin chain synthesis in these patients is not due to a defective promoter, a defective RNA processing or a chain terminator mutation, but rather to impaired regulation of gene expression specific to erythroid cells. The region around the CCAAC box may have a significant role in expression of the delta-globin gene in erythroid cells.

Recent analyses of the whole genome sequencing data enable us to predict cancer incidence for healthy people at present. In addition, metabolome analyses rediscovered that "cancer is a metabolic disease". Importantly, it has been suggested that mitochondrial dysfunction might precede the metabolic change. In this chapter, we would discuss if "cancer is a transcriptional disease". Analyzing 5′-upstream non-protein-encoding regions of the human mitochondrial function-associated genes, we speculate that mitochondrial functions could be recovered or improved at a transcriptional level. In the near future, novel chemo-/gene-therapies might be applied to treat cancer patient converting cancerous cells into normal differentiated cells.