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Profiling microRNA expression during senescence and aging: mining for a diagnostic tool of senescent-cell burden

Weigl, M.; Krammer, T. L.; Pultar, M.; Wieser, M.; Chaib, S.; Suda, M.; Diendorfer, A.; Khamina, K.; Giorgadze, N.; Pirtskhalava, T.; Johnson, K. O.; Inman, C. L.; Ailing, X.; Laemmermann, I.; Meixner, B.; Wang, L.; Xu, M.; Grillari, R.; Ogrodnik, M. B.; Tchkonia, T.; Hackl, M.; Kirkland, J. L.; Grillari, J.

2024-04-10 molecular biology
10.1101/2024.04.10.588794 bioRxiv
Show abstract

In the last decade cellular senescence, a hallmark of aging, has come into focus for pharmacologically targeting aging processes. Senolytics are one of these interventive strategies that have advanced into clinical trials, creating an unmet need for minimally invasive biomarkers of senescent cell load to identify patients at need for senotherapy. We created a landscape of miRNA and mRNA expression in five human cell types induced to senescence in-vitro and provide proof-of-principle evidence that miRNA expression can track senescence burden dynamically in-vivo using transgenic p21high senescent cell clearance in HFD fed mice. Finally, we profiled miRNA expression in seven different tissues, total plasma, and plasma derived EVs of young and 25 months old mice. In a systematic analysis, we identified 22 candidate senomiRs with potential to serve as circulating biomarkers of senescence not only in rodents, but also in upcoming human clinical senolytic trials.

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The top 2 journals account for 50% of the predicted probability mass.

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19
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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.