Hormesis and vitagenes in aging and longevity: Mitochondrial control and hormonal regulation (HMBCI.2013.0051) IF 1,034 citazione n 7

Mitochondria are major cellular sources (and targets) offree radicals, play key roles in the regulation of calciumhomeostasis, and are effectors of the intrinsic apoptoticpathway owing to the release of signaling moleculesthat activate and trigger specific caspase cascades. Mitochondrialdysfunction is inherent in a variety of humandisorders, from the classical mitochondrial diseasesarising from mtDNA mutations (encephalomyopathies)to those involving mitochondrial signaling pathways tothe rest of the cell, modulated by organellar dynamics,and culminating in programmed cell death. The roleof mitochondria in normal aging has been the focus ofextensive research in the last decades and is complementaryto and maturing from the free radical theory ofaging, to the oxidative stress theory of aging, to the mitochondrialoxidative stress theory of aging, and todayaddressing the tight co-regulation of mitochondrialenergy and redox signaling. In this scenario, it appearsthat the function of the carnitine system is a prototypicalvitagene operating at the functional interface of energydistribution between ancestral mechanisms of cell proliferationand differentiation and homeostatic mitochondrial-dependent processes of cell survival, whichrequire energy for cellular stress response and redoxhomeostasis [23]. Very importantly, the new envisionedrole exploited for mitochondrial targeted compounds,such as nutritional antioxidants, carnitines, or carnosine,which, by intersecting convergent mechanisms thatrely on cellular energy distribution and availability suchas cellular stress response pathways, DNA repair, andmolecular fidelity mechanisms as well as maintenanceCornelius et al.: Hormesis and vitagenes in aging and longevity 15of optimum antioxidant potential, appears to be a promisingnovel therapeutic approach for those pathophysiologicalconditions such as neurodegeneration or cancer,where hormetic stimulation of the vitagene pathway isstrongly warrant