Evidence of a pan-tissue decline in stemness during human aging

Abstract

Despite their biological importance, the role of stem cells in human aging remains to be elucidated. In this work, we applied a machine learning methodology to GTEx transcriptome data and assigned stemness scores to 17,382 healthy samples from 30 human tissues aged between 20 and 79 years. We found that ∼60% of the studied tissues present a significant negative correlation between the subject’s age and stemness score. The only significant exception to this pattern was the uterus, where we observed an increased stemness with age. Moreover, we observed a global trend of positive correlations between cell proliferation and stemness. When analyzing the tissues individually, we found that ∼50% of human tissues present a positive correlation between stemness and proliferation and 20% a negative correlation. Furthermore, all our analyses show negative correlations between stemness and cellular senescence, with significant results in ∼80% of the tissues analyzed. Finally, we also observed a trend that hematopoietic stem cells derived from old patients might have more stemness. In short, we assigned stemness scores to human samples and show evidence of a pan-tissue loss of stemness during human aging, which adds weight to the idea that stem cell deterioration contributes to human ageing.