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Modulation of miR-146b Expression during Aging and the Impact of Physical Activity on Its Expression and Chondrogenic
Luca Dalle Carbonare1, Arianna Minoia1, Michele Braggio1
1Department of Engineering for Innovative Medicine, University of Verona, 37100 Verona, Italy.
Abstract:
The finding of molecules associated with aging is important for the prevention of chronic degenerative diseases and for longevity strategies. MicroRNAs (miRNAs) are post-transcriptional regulators involved in many biological processes and miR-146b-5p has been shown to be involved in different degenerative diseases. However, miR-146b-5p modulation has not been evaluated in mesenchymal stem cells (MSCs) commitment or during aging. Therefore, the modulation of miR-146b-5p in the commitment and differentiation of mesenchymal cells as well as during maturation and aging in zebrafish model were analyzed. In addition, circulating miR-146b-5p was evaluated in human subjects at different age ranges. Thus, the role of physical activity in the modulation of miR-146b-5p was also investigated. To achieve these aims, RT (real-time)-PCR, Western blot, cell transfections, and three-dimensional (3D) culture techniques were applied. Our findings show that miR-146b-5p expression drives MSCs to adipogenic differentiation and increases during zebrafish maturation and aging. In addition, miR-146b-5p expression is higher in females compared to males and it is associated with the aging in humans. Interestingly, we also observed that the physical activity of walking downregulates circulating miR-146b-5p levels in human females and increases the number of chondroprogenitors. In conclusion, miR-146b-5p can be considered an age-related marker and can represent a useful marker for identifying strategies, such as physical activity, aimed at counteracting the degenerative processes of aging.
Insights
MicroRNA-146b-5p drives mesenchymal stem cell differentiation and increases with age in zebrafish and humans. Physical activity, like walking, can lower this microRNA in women, suggesting it
Area of Science:
- Molecular Biology
- Aging Research
- Stem Cell Biology
Background:
- MicroRNAs (miRNAs) are key post-transcriptional regulators implicated in aging and degenerative diseases.
- miR-146b-5p is linked to various degenerative conditions, but its role in mesenchymal stem cell (MSC) commitment and aging remains unclear.
- Understanding miRNA modulation is crucial for developing longevity strategies and preventing age-related diseases.
Purpose of the Study:
- To investigate the modulation of miR-146b-5p during mesenchymal cell commitment, differentiation, and aging in a zebrafish model.
- To analyze circulating miR-146b-5p levels in human subjects across different age groups.
- To explore the impact of physical activity on miR-146b-5p levels and related cellular processes.
Main Methods:
- Real-time PCR (RT-PCR) and Western blot analyses were employed.
- Cell transfection and three-dimensional (3D) culture techniques were utilized.
- Circulating miR-146b-5p levels were measured in human participants.
Main Results:
- miR-146b-5p expression promotes MSCs' adipogenic differentiation and elevates during zebrafish maturation and aging.
- Circulating miR-146b-5p levels are higher in females than males and correlate with human aging.
- Walking downregulated circulating miR-146b-5p in females and increased chondroprogenitors.
Conclusions:
- miR-146b-5p serves as a significant age-related biomarker.
- It can be a valuable marker for identifying interventions, such as physical activity, to combat aging-related degeneration.
- This research highlights potential therapeutic targets for promoting healthy aging.
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