Figure 5: Schematic overview of nucleus-mitochondria communication in aging. Decreased SIRT1 activity due to decreased NAD+ levels leads to changes in various gene expression. (1) Decreased PGC-1α/β levels, leading to decline the mitochondria biogenesis. (2) Increased expression of HIF-α, leading to a pseudohypoxia state and, consequently, a missed nucleus-mitochondria communication, driving towards a failure in coding OXPHOS genes. (3) Increased expression of Nf-kB levels, leading to inflammation, plus decreasing NAMPT production, a precursor of NAD+. (4) Decreased expression of FOXO, a factor that participates in cytoprotection. These responses are accompanied by increased ROS levels, a factor that activates AMPK, acting together as factors that counteract the decrease of SIRT1 activity. Increasing the ROS levels from a certain limit promote DNA damage, creating a paradoxical effect. In the mitochondria, the failure in the OXPHOS leads to a decrease in energy supply and, combined with oxidative stress, drive towards mitochondrial dysfunction. These factors combined lead to cellular stress and consequently to senescence. The interaction of oxidative stress and NAD+ levels are still unclear and may be an important source to understand how redox potential controls cellular energy metabolism.