The spleen is a lymphoid organ with multiple functions including blood filtration and immune activity. Aging changes the spleen’s anatomy for both immune and stromal cells and can lead to immunesenescence, contributing to the increased rates of mortality and morbidity commonly observed in the elderly. Much evidence indicates that the combination of food quantity and quality can influence chronic inflammatory states in the spleen. Quantitative amino-acids (AA) adequacy is pivotal to maintain cell integrity in mammals. Aged mice feed with balanced essential-AA (EAA) formulation improved mitochondrial biogenesis and morphological and molecular changes in many organs, as well as increased lifespan. Here, we evaluated the inflammatory state of the spleen in aged male mice (fifteen months old) chronically fed for twelve months with a particular EAA-rich diet compared to a standard laboratory diet. This study found that chronic consumption of an EAA-rich diet decreased inflammation and modulated reticular and mitochondrial chaperones, mitochondrial function and cells survival, maintaining the correct architecture of the spleen. These changes could also be beneficial for immune system integrity, providing a possible theoretical-speculative basis for the role of EAA improving the quality of life of the elderly by probably slowing immune-senescence.