Reactive oxygen species (ROS) is a group of species that includes hydrogen peroxide (H2O2), superoxide ion (O2•-) and hydroxyl radical (•OH). They are outcomes of the oxidative metabolism in mitochondria, typically scavenged by the superoxide dismutase (SOD) enzyme. Upon mitochondrial malfunction, ROS are released producing oxidative damage to mitochondrial and cellular DNA. These reactions signal a DNA damage response similar to that produced by telomere shortening, causing senescence. Thus, changes in mitochondrial biology resulting in enhanced ROS concurrently alter epigenetic status at the DNA methylation level. Moreover, DNA methylation and histone acetylation vary upon aging and convey modifications in expression of mitochondrial genes, thus producing a feedback loop of failing mitochondrial function. Senescent cells undergo significant changes in their mitochondrial function, dynamics, and morphology. They exhibit decreased membrane potential, higher proton leak, intensified enzyme release, higher mass, and higher amount of tricarboxylic acid cycle metabolites. The number of mitochondria in senescent cells is enhanced, due to the accumulation of old and dysfunctional mitochondria because of deficient mitophagy (mitochondrial removal). Furthermore, mitophagy deficiency appears as a distinct mechanism for mitochondrial mass expansion. Regardless of their abundance, mitochondria in senescent cells typically exhibit a lower ability to produce ATP. Instead, senescent cells are characterized by a Warburg shift (a shift from oxidative phosphorylation to rapid aerobic glycolysis); this produces more ROS, thus causing protein and lipid damage, telomere shortening, and DNA damage response. • Accumulation of sphingolipids & dysregulation of cholesterol metabolism