Dos Santos Gabriel Arantes, Magdaleno Gustavo Daniel Vega, de Magalhães João Pedro
Laboratory of Medical Investigation (LIM55), Urology Department, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo 01246 903, Brazil.
Genomics of Ageing and Rejuvenation Lab, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2WB, United Kingdom.
Aging (Albany NY). 2024 Apr 4;16(7):5796-5810. doi: 10.18632/aging.205717.
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 exhibit a significant negative correlation between the subject's age and stemness score. The only significant exception was the uterus, where we observed an increased stemness with age. Moreover, we observed that stemness is positively correlated with cell proliferation and negatively correlated with cellular senescence. Finally, we also observed a trend that hematopoietic stem cells derived from older individuals might have higher stemness scores. In conclusion, 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 may contribute to human aging.
尽管干细胞具有生物学重要性,但其在人类衰老过程中的作用仍有待阐明。在这项研究中,我们将机器学习方法应用于GTEx转录组数据,并为来自30种人体组织、年龄在20至79岁之间的17382个健康样本赋予了干性评分。我们发现,约60%的研究组织在受试者年龄和干性评分之间呈现出显著的负相关。唯一显著的例外是子宫,在子宫中我们观察到干性随年龄增长而增加。此外,我们观察到干性与细胞增殖呈正相关,与细胞衰老呈负相关。最后,我们还观察到一种趋势,即来自老年个体的造血干细胞可能具有更高的干性评分。总之,我们为人类样本赋予了干性评分,并证明了在人类衰老过程中存在全组织干性丧失的证据,这进一步支持了干细胞退化可能导致人类衰老的观点。