Transcriptomic signals of mitochondrial dysfunction and OXPHOS dynamics in fast-growth chicken

INTRODUCTION: Birds are equipped with unique evolutionary adaptations to counter oxidative stress. Studies suggest that lifespan is inversely correlated with oxidative damage in birds. Mitochondrial function and performance are critical for cellular homeostasis, but the age-related patterns of mitochondrial gene expression and oxidative phosphorylation (OXPHOS) in birds are not fully understood. The domestic chicken is an excellent model to understand aging in birds; modern chickens are selected for rapid growth and high fecundity and oxidative stress is a recurring feature in chicken. Comparing fast- and slow-growing chicken phenotypes provides us an opportunity to disentangle the nexus of oxidative homeostasis, growth rate, and age in birds. METHODS AND RESULTS: We compared pectoralis muscle gene expression patterns between a fast and a slow-growing chicken breed at 11 and 42 days old. Using RNAseq analyses, we found that mitochondrial dysfunction and reduced oxidative phosphorylation are major features of fast-growth breast muscle, compared to the slow-growing heritage breed. We found transcriptomic evidence of reduced OXPHOS performance in young fast-growth broilers, which declined further by 42 days. DISCUSSION: OXPHOS performance declines are a common feature of aging. Sirtuin signaling and NRF2 dependent oxidative stress responses support the progression of oxidative damage in fast-growth chicken. Our gene expression datasets showed that fast growth in early life places immense stress on oxidative performance, and rapid growth overwhelms the OXPHOS system. In summary, our study suggests constraints on oxidative capacity to sustain fast growth at high metabolic rates, such as those exhibited by modern broilers.