Abstract Background Aging-related production decline is widely observed in poultry farming, making it challenging to prolong the laying cycle of hens. However, its genetic determinants remain unclear. This study aimed to systematically identify key genes associated with hens with age-related production decline and reveal dynamic changes in gene expression during tissue functional decline. Results This study integrated multi-tissue transcriptomic data from 216 samples obtained from Rhode Island Red laying hens, covering nine tissues (hypothalamus, pituitary, cecum, duodenum, liver, ovary, magnum, isthmus, and uterus) at three age points (50, 70, and 100 weeks of age). Through comprehensive analysis, we identified 87 genes that showed significant changes across all nine tissues (|log 2 -fold change| > 1, FDR < 0.05) and 20 hub genes playing critical roles in mitochondrial and ribosome functions. In addition, we identified 106 differentially expressed genes (DEGs) with tissue-specific expression patterns and interaction networks. We further screened 51 genes that are associated with both the age-related production decline process and economically important traits in chickens. Finally, functional validation using a hydrogen peroxide-induced senescence model in DF-1 cells highlighted NDUFB9 , a gene associated with mitochondrial respiratory chain complex I, as a potential anti-aging target. Conclusions This study provides a systematic multi-tissue transcriptomic framework for understanding aging-associated productivity decline in laying hens. Our findings highlight conserved mitochondrial and ribosomal dysfunction as key molecular features of age-related production decline and identify NDUFB9 as a potential anti-aging target, offering valuable insights for improving poultry longevity and production performance. Graphical Abstract
Gao et al. (Tue,) studied this question.