The effects of age on mitochondrial respiration occur in sex-specific ways. A-B.
Systems- level view of the total relative change (sum of all relative changes) present at each mitochondrial parameter (respiration via CI, CII, or CIV) for males (M) and females (F), respectively. All change is old (O) compared to young (Y). C. Heat maps of O / Y data for each mitochondrial parameter per tissue across lifespan. Male and female values are grouped and organized by greatest (top) to least (bottom) sum of relative change per tissue. Tissues with the largest positive relative change as a result of aging are located on the top-most region of the heat maps, while those with the largest negative relative change are at the bottom. The middle of each heat map represents tissues with little relative response to aging or with opposite effect directions across sex. D. Graphs showing magnitude of sex-effect with age across all tissues and mitochondrial parameters (CI, CII, or CIV). The blue line and circles represent log2(old male/young male) data and the red line and boxes represent log2(old female/young female) data; both linked to the left y-axis. The black line and triangles represent the absolute difference of male and female relative change data (linked to the right y-axis). All data is organized from left to right by highest to lowest absolute difference of relative change across sex. Tissues with the greatest relative difference across sex are located to the left-most region of the graph, while those with the most similar response to aging are located to the right. A hollow blue circle, red circle, and black triangle represent a tissue with a divergent sex-specific age response. E. Summary diagrams classifying the relative trends of each mitochondrial parameter assayed per tissue as age- or age-and-sex-specific. Age-specific effects have a shared relative change direction across sex. Tissues in the red “M + F Increased” box have a positive relative change for both males and females. Tissues in the blue “M + F Decreased” box have a negative relative change for both males and females. Tissues in the Purple box labeled “Divergent” have opposing log2(O/Y) directions (signs, + or -) for male and female values; these tissues display relative mitochondrial changes that are age-and-sex-specific. F. Summary diagram showing tissues with a shared increase (red box) or decrease (blue box) consistent across all complexes (CI, CII, and CIV). Tissues within the shared increase or decrease classifications are grouped by their tissue-type, for example. PL, DI, SL, and HV are all muscle, CO, HI, HY, and CE are all brain and so on. CI = respiration measured through complex I stimulated by NADH; CII = respiration through complex II stimulated by succinate in the presence of rotenone; CIV = respiration at complex IV stimulated by TMPD and ascorbate in the presence of rotenone and antimycin A. Tissues: BT = brown adipose tissue, CC = cecum, CE = cerebellum, CO =brain cortex, DI = diaphragm, DC = distal colon, DU = duodenum, EY = eyes, GS = gastrocnemius, GW = gonadal white adipose tissue, HS = hamstring, HA = heart atria, HV = heart ventricles, HI = hippocampus, HY = hypothalamus, IL = ileum, IW = inguinal white adipose tissue, JE = jejunum, KC = kidney cortex, KM = kidney medulla, LV = liver, LN = lung, MW = mesenteric white adipose tissue, PN = pancreas, PL = plantaris, PC = proximal colon, QD = quadriceps, SK = skin, SL = soleus, SP = spleen, ST = stomach, TN = tongue. Reproductive organs are omitted from cross-sex analysis.