Mitochondrial dysfunction, characterized by decreased efficiency of the Electron Transport Chain (ETC) and loss of structural integrity, is linked to cellular senescence, an irreversible end to the cell-division cycle that contributes to aging. Minimizing senescence through late age intervention may prevent aging tissue dysfunction. Systematic treatment of old mice with a tetrapeptide, SS-31 reduced mitochondrial dysfunction and senescence in kidneys. We hypothesized that a similar effect would occur in other organs, and with other mitochondrial targeting interventions. These interventions included the SS-31 tetrapeptide which interacts with mitochondrial cardiolipin to improve structure and function, and NMN (Nicotinamide Mononucleotide), which fuels the organelle for more efficient adenosine triphosphate generation through the ETC. We treated old mice at 24 months-of-age for 8 weeks with either SS-31, NMN, or both interventions combined. Control groups included young-untreated mice at 4 months-of-age and old-untreated mice sacrificed with the treatment groups at 26 months-of-age. By comparing tissues, including heart, kidney, liver, skeletal muscle, skin and brain, within individual mice, we were able to account for differing rates of aging between mice. To determine the relative levels of senescence and treatment response in each tissue, we used Immunohistochemistry to quantify known senescence markers p16 and HMGB1, and quantitative-PCR to measure p16 mRNA transcript levels. As expected, preliminary results from p16 staining showed higher overall senescence burden in old as compared to young mice. The staining patterns also revealed senescence susceptible cells, with majority of p16 positivity in liver satellite cells, glomeruli and tubules of kidney, fibrocytes of heart and myocytes of skeletal muscle. Overall, the kidney and liver had more p16 positive senescent cells than did heart and muscle. These tissues are currently under analysis to determine whether intervention treatments can reduce cellular senescence.