Age- and glycemia-related miR-126-3p levels in plasma and endothelial cells
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Circulating miR-126-3p levels were determined in 136 healthy subjects (CTRs) aged 20-90 years and 193 patients with type-2 diabetes mellitus (T2DMs) aged 40-80 years, to explore the combined effect of age and glycemic state on miR-126-3p expression. Moreover, intra/extracellular miR-126-3p levels were measured in human endothelial cells (HUVECs) undergoing senescence under normo/hyper-glycemic conditions. Plasma miR-126-3p was significantly higher in the oldest compared with the youngest CTRs ( <45 vs. >75 years; relative expression: 0.27±0.29 vs. 0.48±0.39, p=0.047). Age-based comparison between CTRs and T2DM demonstrated significantly different miR-126-3p levels only in the oldest (0.48±0.39 vs. 0.22±0.23, p<0.005). After multiple adjustments, miR-126-3p levels were seen to be lower in patients with poor glycemic control, compared with age-matched CTRs. The age-related increase in plasma miR-126-3p found in CTRs was paralleled by a 5/6-fold increase in intra/extracellular miR-126-3p in in vitro-cultured HUVECs undergoing senescence. Notably, significant down- regulation of SPRED-1 protein, a validated miR-126-3p target, was found in senescent HUVECs. Moreover, miR-126-3p expression was down-regulated in intermediate-age HUVECs grown in high-glucose medium until senescence. Aging/senescence-associated miR-126-3p up-regulation is likely a senescence-associated compensatory mechanism that is blunted when endothelial cells are exposed to high glucose levels, a phenomenon that probably occurs in vivo in T2DM patients.
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miR-25-3p, miR-92a-3p, miR-93-5p, miR-101-3p, miR-106b-5p, miR-142-5p, miR-151a-3p, and miR-181a-5p tend to be under-represented, whereas miR-21-5p and miR-126-3p are over-represented at older ages.
“Nonetheless, miR-25–3p, miR-92a-3p, miR-93–5p, miR-101–3p, miR-106b-5p, miR-142–5p, miR-151a-3p, and miR-181a-5p tend to be under-represented, whereas miR-21–5p and miR-126–3p are over-represented at older ages47,49,50.”
From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [50]
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- Authors
- Olivieri, F., Bonafè, M., Spazzafumo, L., Gobbi, M., Prattichizzo, F., Recchioni, R., Marcheselli, F., Sala, L. L., Galeazzi, R., Rippo, M. R., Fulgenzi, G., Angelini, S., Lazzarini, R., Bonfigli, A. R., Brugè, F., Tiano, L., Genovese, S., Ceriello, A., Boemi, M., Franceschi, C., Procopio, A. D., & Testa, R.
- Affiliations
- Marche Polytechnic University (IT)
- Istituto Ortopedico Rizzoli (IT)
- Istituto Nazionale di Riposo e Cura per Anziani (IT)
- Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas (ES)
- University of Bologna (IT)
- MultiMedica (IT)
- Corresponding author
- Olivieri, Fabiola
- ORCID
- Olivieri, Fabiola
- Bonafè, Massimiliano
- Spazzafumo, Liana
- Prattichizzo, Francesco
- Recchioni, Rina
- Marcheselli, Fiorella
- Sala, Lucia La
- Galeazzi, Roberta
- Rippo, Maria Rita
- Fulgenzi, Gianluca
- Angelini, Sabrina
- Lazzarini, Raffaella
- Bonfigli, Anna Rita
- Tiano, Luca
- Genovese, Stefano
- Ceriello, Antonio
- Franceschi, Claudio
- Procopio, Antonio Domenico
- Testa, Roberto
- Venue
- Aging
- Publisher
- Impact Journals, LLC
- Published
- 2014-10-07
- Volume
- 6
- Issue
- 9
- Pages
- 771-786
- ISSN
- 1945-4589 (ISSN-L)
- PMC
- PMC4221921
- OpenAlex
- W2153009056
- Cited by
- 118
- References
- 71
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 5 · 2023: 11 · 2022: 14 · 2021: 11 · 2020: 14 · 2019: 14 · 2018: 9 · 2017: 13 · 2016: 12 · 2015: 6
- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Aging (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- miR-126-3p, microRNA, type 2 diabetes, glycemic control, endothelial cell senescence, high glucose, plasma microRNA, endothelial dysfunction, vascular aging
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Diabetes Mellitus, Type 2, Female, Humans, Hyperglycemia, Male, Middle Aged, Case-Control Studies, MicroRNAs, Endothelial Cells, Young Adult, Human Umbilical Vein Endothelial Cells
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