Figure 2

a,b. Vitagenes and the pathway of cellular stress response. Cumulating misfolded proteins in response to proteotoxic environmental stress conditions triggers the cellular stress response (Figure 2a). HSPs that are normally bound to HSF1, maintaining it in a repressed state before stress, are titrate away by damaged or misfolded proteins with resulting HSF-1 activation. Multi-step activation of HSF1 involves post-translational modifications, such as hyperphosphorylation and deacetylation, 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, including carnosic acid, resveratrol, sulforaphane, dimethyl fumarate, acetyl-L-carnitine or carnosine are able to activate vitagenes, such as heme oxygenase, Hsp70, thioredoxin reductase and sirtuins which represent an integrated system for cellular stress tolerance. Phytochemicals and Acetyl-L-carnitine act through the activation of the vitagene system, with up-regulation of HO-1, Thioredoxin, the GSH and Sirtuin system, results in counteraction of pro-oxidant conditions (Figure 2b). During aging, 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.