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.
Competing Interest Statement
JPM is CSO of YouthBio Therapeutics, an advisor/consultant for the Longevity Vision Fund and NOVOS, and the founder of Magellan Science Ltd, a company providing consulting services in longevity science.
Footnotes
Conflict of interest: JPM is CSO of YouthBio Therapeutics, an advisor/consultant for the Longevity Vision Fund and NOVOS, and the founder of Magellan Science Ltd, a company providing consulting services in longevity science.
Funding: Gabriel Arantes dos Santos is financed by the scholarship “Bolsa de Excelência em Medicina Domingos Nelson Martins” of the Faculty of Medicine of the University of São Paulo (FMUSP). Work in our lab is supported by grants from the Wellcome Trust (208375/Z/17/Z), Longevity Impetus Grants, LongeCity and the Biotechnology and Biological Sciences Research Council (BB/R014949/1 and BB/V010123/1).