Aging gene signatures in rodent tissues

In order to get a greater understanding as to the genes and signaling pathways which are up- or down-regulated in a consistent manner throughout the rodent lifespan, we generated a high N age-related gene expression atlas in mice and rats, by profiling 28 tissues in male and female C57BL/6J mice, and 32 tissues in male Sprague Dawley rats (> 5000 samples) over multiple time points. We identified age-related genes and pathways that change either early in life, at mid-age, late in life, or linearly. Linear genes dominated many but not all tissues, and certain tissues (e.g. gut tissues) were relatively spared from age-related changes. Genes which encode proteins involved in the immune and inflammatory response increased, mostly linearly, in many tissues in both species, with rats showing a weaker response. We identified tissues that showed a strong sex bias or species bias: in mice, the pituitary gland and hypothalamus show more age-related pathways in females, while femur, fat, liver and duodenum are more male biased. Between species, soleus, colon, and jejunum in rats showed more changes with age, while cerebellum, hippocampus, right ventricle etc. were biased towards male mice. Sex bias and species bias in a pathway were often due to a few tissues rather than a pan-tissue difference. For example, pathways related to glucose metabolism and mitochondrial respiration were down-regulated in the rat skeletal muscles, but not in those of mice. Correlation analyses by tissue aging revealed that highly correlated tissues are predominately from the same organ (e.g. the various heart chambers correlated) or have interconnected functions (e.g. spinal cord and skeletal muscles in rats). More tissues showed correlated aging in male mice than in female mice or male rats.