In this new study, researchers provide the first evidence of a pan-tissue decrease of stemness during human aging.
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Aging is still shrouded in proverbial darkness. But, some researchers hypothesize that aging may be linked to stem cell exhaustion. Stemness, the ability of a cell to differentiate into various cell types, is an essential characteristic defining the functionality of stem cells. It has been observed that stem cells seem to diminish with age, although the precise role of stem cells in human aging remains to be elucidated.
“Among the biological pathways associated with aging, we can highlight stem cell exhaustion, which argues that during normal aging, the decrease in the number or activity of these cells contributes to physiological dysfunction in aged tissues [4].”
In a new study, researchers Gabriel Arantes dos Santos, Gustavo Daniel Vega Magdaleno and João Pedro de Magalhães from the Universidade de Sao Paulo, University of Birmingham and the University of Liverpool applied a machine learning method to detect stemness signatures from transcriptome data of healthy human tissues. Their research paper was published on April 4, 2024, and chosen as the cover of Aging’s Volume 16, Issue 7, entitled, “Evidence of a pan-tissue decline in stemness during human aging.”
The Study
In this study, the researchers delve into the intricate relationship between aging and stemness, offering vital insights into this complex interplay. The researchers conducted an in-depth analysis of healthy human tissue samples, assigning “stemness scores” to track the stemness levels across different age groups.
“In this context, detecting stemness-associated expression signatures is a promising strategy for studying stem cell biology.”
This research is the first to provide evidence of a pan-tissue decline in stemness during human aging. It is an important step forward in understanding the cellular mechanisms involved in the aging process and their potential implications for human health.
Methodology & Data Sources
The researchers used the RNA-Seq-based gene expression data from human tissues, downloaded from the Genomics of Ageing and Rejuvenation Lab’s Genomics of Ageing (GTEx) portal. This comprehensive dataset included over 17,000 healthy human tissue samples, spanning an age range of 20 to 79 years.
A machine learning methodology, originally developed by Malta et al., was applied to the GTEx transcriptome data to assign stemness scores to all samples. This advanced machine learning model was trained on stem cell classes and their differentiated progenitors, enabling the researchers to detect stemness signatures from the transcriptome data of healthy human tissues.
Key Findings
The analysis revealed a significant negative correlation between the subject’s age and stemness score in approximately 60% of the studied tissues. Interestingly, the only exception was the uterus, which exhibited increased stemness with age. This finding is particularly noteworthy, as it provides the first evidence of a pan-tissue decline in stemness during human aging. It supports the hypothesis that stem cell deterioration may contribute to the aging process.
The researchers also observed interesting correlations between stemness and other cellular processes. They found that stemness was positively correlated with cell proliferation. However, this relationship was not universal, with some tissues showing exceptions.
In contrast, when they examined the association between stemness and cellular senescence, a negative correlation was observed across the board. This finding suggests that although senescent cells and stem cells are not technically opposite states, they behave in opposite ways at the transcriptomic level within a living organism.
Implications & Future Directions
The findings of this study have far-reaching implications for our understanding of the aging process and its cellular underpinnings. By providing the first evidence of a pan-tissue decline in stemness during human aging, the study adds significant weight to the notion that stem cell deterioration may contribute to human aging.
However, many questions remain. For instance, it is not yet clear whether the loss of stemness contributes to aging or is a consequence of it. Moreover, it is uncertain whether the decline in stemness is due to a direct reduction in the stem cell pool or refers to intrinsic changes in different cells within the tissue.
Further research is needed to address these questions, and more robust studies are required to draw more assertive conclusions. It is also crucial to determine which factors drive these changes and which patterns and genes are associated with this process. This will be pivotal in advancing our understanding of stemness aging and its potential implications for human health.
“In conclusion, we provide the first evidence of a pan-tissue decrease of stemness during human aging and report an association between stemness and cell proliferation and senescence. This study also assigned a stemness score to more than 17,000 human samples, and these data can be useful for the scientific community for further studies.”
Click here to read the full research paper published in Aging.
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Aging is an open-access, traditional, peer-reviewed journal that publishes high-impact papers in all fields of aging research. All papers are available to readers (at no cost and free of subscription barriers) in bi-monthly issues at Aging-US.com.
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