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Study from CABD and UGR discovered that cellular aging affects gene expression and messenger RNA maturation

Researchers from the Andalusian Center for Developmental Biology and the University of Granada demonstrate that changes in stem cell behavior during aging are accompanied by modifications (at the level of gene expression and mRNA processing) in the transcriptome of niche cells.

This work highlights the importance of studying the molecular processes that occur during aging.

A study led by Acaimo González Reyes, from the Andalusian Center for Developmental Biology (CABD) - a joint center of the Spanish National Research Council (CSIC), the Pablo de Olavide University of Seville and the Andalusian Regional Government - and Federico Zurita, from the University of Granada, describes for the first time the aging mechanisms of the cells that make up a stem cell niche. The study was carried out in collaboration with Manuel Irimia's group (CRG) and Gretel Nusspaumer (CABD).

The work, published in the prestigious journal Nature Communications, analyzes in depth the molecular profile of aging cells that form a stem cell niche. To do this, they have taken as a study model the ovary of the fruit fly (Drosophila melanogaster), which is composed of several cell types and is an example of a well-defined stem cell niche. This research has allowed the study of functional changes in both gene expression and maturation of messenger RNAs during aging.

Gene expression contributes to the formation of new interaction networks with potentially significant cellular functions. The Drosophila melanogaster germline stem cell niche comprises three supporting cell types whose transcriptomes during aging undergo differential variations in gene expression and maturation of messenger RNAs related to cell adhesion, cytoskeleton, and neuronal signaling, among others. Because each cell population showed distinctive changes in these molecular features, niche cell types have been shown to possess unique aging signatures. “It is surprising that cells so closely related to each other, due to their origin and function, age so differently,” says CABD researcher Acaimo González Reyes.

Likewise, the research has made it possible to establish that the cells of the niche, as they age and modify their transcriptome (which genes, and how much they are expressed) and the maturation of messenger RNAs, can do so in a coordinated manner. “We observed that groups of genes showed changes in both gene expression and mRNA maturation, revealing a coordinated regulation of both during niche aging,” explains one of the senior researchers of the study, Federico Zurita (UGR).

In fact, one of the genes responsible for the correct processing of mRNAs, the Smu1 gene, itself undergoes maturational changes with age, providing a molecular mechanism to explain the coordination between the two phenomena during aging.


The next challenge of this research will be to demonstrate the universality of the findings of this work. This would help to understand why, with age, stem cell populations are less efficient at producing new cells or regenerating tissue damage, as observed with the appearance of gray hair or the increased difficulty of wound healing. Increased knowledge can contribute to the biomedical field to solve problems related to aging.

Reference:
Even-Ros, D., Huertas-Romero, J., Marín-Menguiano, M. et al. Drosophila ovarian stem cell niche ageing involves coordinated changes in transcription and alternative splicing. Nat Commun 16, 2596 (2025). https://doi.org/10.1038/s41467-025-57901-8