Selection-, age-, and exercise-dependence of skeletal muscle gene expression patterns in a rat model of metabolic fitness

Aerobic exercise capacity can influence many complex traits including obesity and type 2 diabetes. We established two rat lines by divergent selection of intrinsic aerobic capacity. The high capacity runners (HCR) and low capacity runners (LCR) differed by ~9-fold in aerobic capacity after 32 generations, and diverged in body fat, blood glucose, and other health indicators. To study the interplay among genetic differentiation, age, and strenuous exercise, we performed microarray-based gene expression analyses in skeletal muscle with a 2×2×2 design to compare HCR and LCR, old and young animals, and between rest and exhaustion, for a total of eight groups (n=6 each). Transcripts for mitochondrial function are expressed higher in HCR than LCR at both rest and exhaustion, for both age groups. Extracellular matrix components decrease with age in both lines and both rest and exhaustion. Interestingly, age-effects in many pathways are more pronounced in LCR, suggesting that HCR's higher innate aerobic capacity underlies both increased lifespan and heathspan.