Mitochondrial dysfunction is characterized by loss of structural integrity and decreased efficiency of the Electron Transport Chain. These changes are linked to cellular senescence, an irreversible end to the cell-cycle that contributes to aging phenotypes and is marked by a cellular senescence-associated secretory phenotype. Understanding this impact of late age mitochondrial dysfunction interventions will contribute to the field of, ‘senolytics’, anti-senescent drugs dedicated to improving health span. Previously, systematic treatment of old mice with tetrapeptide, Elamipretide (ELAM), which interacts with the inner mitochondrial membrane to improve cristae structure and function, reduced mitochondrial dysfunction and senescence in kidney and heart. We hypothesized that additional intervention with Nicotinamide Mononucleotide (NMN), a NAD+ precursor, which contributes to adenosine triphosphate generation, would supplement this finding by enhancing mitochondrial energetic capability and decreasing mitochondrial dysfunction and senescence in aged kidneys. Liver was selected to clarify intervention effects as global vs. kidney-specific mechanisms. Old mice were treated at 24 months-old (mo) for 8 weeks with: ELAM through osmotic pump (3mg/kg), NMN via drinking water (300mg/kg), or both simultaneously. Untreated control mice were 4 mo (young) and 26 mo (old). Contrary to our hypothesis, NMN treatment proved detrimental in kidney by increasing mRNA expression of IL-1b, an inflammatory cytokine, relative to untreated aged mice. Further exploration of IL-1b downstream targets showed consistent upregulation of CCL2, an inflammatory chemokine and KIM-1, a marker of proximal tubule injury in NMN treated mice. ELAM, however, provided rescue in the coupled treatment group, by significantly reducing mRNA expression of IL-1b and CCL2 relative to NMN alone. These data suggest that ELAM lessens senescent burden by reducing renal inflammation; conversely NMN exacerbates existing inflammation pathways in aged kidneys. This result was not observed in liver, demonstrating tissue specificity. Further work will investigate the cellular source of inflammation through RNA in situ hybridization.