The heart proteome and phosphoproteome were analyzed in young (5-6-month old), old (24-month old at the start of the study), and elamipretide-treated (for 8 weeks) old mice using shotgun proteomics methods in order to assess the effects of aging on signaling and the ability of mitochondrion-targeted drug elamipretide (SS-31) to reverse age-related changes. Enhancement and suppression of phosphorylation at sites along a variety of proteins was found to occur with age. Elamipretide treatment partially restored the phosphorylation state of proteins that had increased phosphorylation with age, but did not have a large effect those that had decreased phosphorylation with age.