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 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.

Keywords: longevity; senescence; stem cells; transcriptomics.

Figure 1

Stemness levels during human aging. (A) Distribution of stemness in human tissues. (B) Heatmap of Pearson’s correlation coefficient between stemness scores and age in human tissues. (C) Linear trend between stemness scores and age in human tissues. *FDR <0.05.

Figure 2

Stemness in same individual and validation datasets. (A) Correlation matrix between stemness across tissues from the same individual (excluding sex-related tissues) from GTEx. Numbers in each square represent the Pearson correlation coefficient. (B) Stemness levels of different groups in the alternative bone dataset, data from Weivoda et al. [30]. (C) Correlation between stemness and aging in an alternative lung dataset (r = -0.22, p-value = 0.045), data from Lee et al. [31]. (D) Correlation between stemness and aging in an alternative muscle dataset (r = -0.11, p-value = 0.42), data from Tumasian et al. [32].

Figure 3

Relationship between stemness, cellular proliferation and senescence. (A) Correlation between stemness score and MKI67 expression. (B) Heatmap of Pearson’s correlation coefficient between stemness scores and MKI67 expression. (C) Correlation between stemness score and senescence scores. (D) Heatmap of Pearson’s correlation coefficient between stemness score and senescence score. *FDR <0.05.

Figure 4

Stemness levels in hematopoietic stem cells. (A) Direct comparison between young and old groups. (B) Correlation between stemness score and age of the HSC donors.