Deciphering the Transcriptomic Signatures of Aging Across Organs in Mice

Aging is a key risk factor for disease in mammals, yet its molecular basis across organs remains unclear. Here, we performed bulk RNA sequencing on eight organs (brain, heart, kidney, liver, lung, skeletal muscle, spleen, testis) from male C57BL/6J mice at distinct life stages. Our analysis revealed that age-related transcriptomic shifts vary in timing and magnitude: early in lung, spleen, testis; mid-life in heart, kidney, skeletal muscle; and late in brain and liver. Magnitude ranged from very low (testis), low (brain, heart), moderate (lungs, skeletal muscle) to high (kidneys, liver, spleen). We uncovered organ-specific aging signatures, for instance, mitochondrial and epigenetic regulation in the kidney, metabolic/detoxification in the lung, and angiogenesis as well as ribosome biogenesis in the spleen). We also identified shared transcriptomic signatures, such as cellular senescence in the kidney and skeletal muscle, ECM remodeling in the heart, skeletal muscle and spleen), or inflammation in the heart, kidney, liver and lungs. These findings highlight unique and overlapping transcriptomic aging signatures, informing future therapeutic strategies to improve healthspan. Overall design: Towards addressing some of the shortcomings from previous studies, we employed an experimental design with a relatively large sample size (n = 45), 6 time points- 3, 5 (both young adult), 8 (adult), 14 (mid-life), 20 and 26 (late life) months and profiled overall age-associated transcriptomic changes in 8 organs harvested from male C57BL/6J mice, using the likelihood ratio test (LRT).