Fig. 1

Vitagenes and the pathway of cellular stress response. Proteotoxic stresses causing accumulation of misfolded proteins trigger the cellular stress response. HSPs that are normally bound to HSF1 are titrate away by damaged proteins with resulting HSF-1 activation. Multi-step activation of HSF1 involves post-translational modifications, such as hyperphosphorylation, deacetylation or sumoylation, which allow HSF1 to trimerize, translocate into the nucleus, and bind to heat-shock elements (HSEs) in the promoter regions of its target hsp genes. Nutritional antioxidants, are able to activate vitagenes, such as heme oxygenase, Hsp70, thioredoxin reductase and sirtuins which represent an integrated system for cellular stress tolerance. Activation of Vitagene system, with up-regulation of HO-1, Thioredoxin, GSH and Sirtuin, results in reduction of pro-oxidant conditions. During inflammaging, including aged-associated pathologies a gradual decline in potency of the heat shock response occur and this may prevent repair of protein damage, leading to degeneration and cell death of critical parenchymal cells. Phytochemicals and acetylcarnitine act through the activation of transcription factor Nrf2, which after binding to the antioxidant responsive element up-regulates vitagenes