In this manuscript, I discuss the direct link between abnormalities in inflammatory responses, mitochondrial metabolism and autophagy during the process of aging. It is focused on the cytosolic receptors nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) and cyclic GMP-AMP synthase (cGAS); myeloid-derived suppressor cells (MDSCs) expansion and their associated immunosuppressive metabolite, methyl-glyoxal, all of them negatively regulated by mitochondrial autophagy, biogenesis, metabolic pathways and its distinct metabolites.