Platelets from young and old mice have a distinctive mitochondrial respiration and metabolome. (A) Bioenergetics Seahorse analysis of platelets from young and old mice shows that platelets from old mice have significantly higher respiration upon activation with 0.1 U/mL thrombin (n = 4-6 mice per group; mean plus or minus SEM). (B) Platelet metabolomics experimental approach. (C) Partial least squares discriminant analysis (PLS-DA) of platelets from young and old mice at resting and activated state shows distinctive metabolomic profiles of platelets due to age and activation (n = 4 mice per group; plus or minus SEM). (D) Pentose phosphate pathway metabolites of platelets from old mice are elevated at baseline and show preferential glycolytic metabolism at baseline. (E) TCA cycle upstream metabolites glucose, pyruvate, and lactate between platelets of young and old mice. (F) Differences in the adenylates AMP, ADP, and ATP between platelets from young and old mice. *P < .05; **P < .01; and ***P < .001. Student t test and Mann-Whitney test. AU, arbitrary unit; FCCP, carbonylcyanide p-trifluoromethoxyphenylhydrazone; LC-MS, liquid chromatography–mass spectrometry; R/A, rotenone/antimycin A.