Characterizing expression changes in noncoding RNAs during aging and heterochronic parabiosis across mouse tissues.

Nature biotechnology 2024 Jan

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Molecular mechanisms of organismal and cell aging remain incompletely understood. We, therefore, generated a body-wide map of noncoding RNA (ncRNA) expression in aging (16 organs at ten timepoints from 1 to 27 months) and rejuvenated mice. We found molecular aging trajectories are largely tissue-specific except for eight broadly deregulated microRNAs (miRNAs). Their individual abundance mirrors their presence in circulating plasma and extracellular vesicles (EVs) whereas tissue-specific ncRNAs were less present. For miR-29c-3p, we observe the largest correlation with aging in solid organs, plasma and EVs. In mice rejuvenated by heterochronic parabiosis, miR-29c-3p was the most prominent miRNA restored to similar levels found in young liver. miR-29c-3p targets the extracellular matrix and secretion pathways, known to be implicated in aging. We provide a map of organism-wide expression of ncRNAs with aging and rejuvenation and identify a set of broadly deregulated miRNAs, which may function as systemic regulators of aging via plasma and EVs. © 2023. The Author(s).

Citation

Viktoria Wagner, Fabian Kern, Oliver Hahn, Nicholas Schaum, Nicole Ludwig, Tobias Fehlmann, Annika Engel, Dominic Henn, Shusruto Rishik, Alina Isakova, Michelle Tan, Rene Sit, Norma Neff, Martin Hart, Eckart Meese, Steve Quake, Tony Wyss-Coray, Andreas Keller. Characterizing expression changes in noncoding RNAs during aging and heterochronic parabiosis across mouse tissues. Nature biotechnology. 2024 Jan;42(1):109-118