The use of betaine as a novel senotherapy

Tran, Ngoc Uyen (2025) The use of betaine as a novel senotherapy. PhD thesis, University of Glasgow.

Abstract

Background: The global population demographic comprising those aged 65 years and over is increasing. Despite an increase in human life expectancy over the past 150 years, this has not been matched by a similar increase in health span (i.e. years of disease free living). Consequently, ageing populations present with more age-/lifestyle related diseases such as cardiovascular disease (CVD), chronic kidney disease (CKD) and cancer as part of a diseasome of ageing. Betaine is a key component of one-carbon metabolism required physiologically as an osmolyte, an antioxidant and a methyl donor for maintenance of the epigenetic landscape of ageing and mitochondrial function.

Objectives: The present study aims to assess how dysregulated ageing underpins the development of vascular ageing and the effects of betaine to mitigate this.

Methods: A series of experiments using real time cell analysis (RTCA), transcriptomics, immmunohistochemistry, immunocytochemistry and real-time PCR for a range of validated biomarkers of vascular ageing have been investigated in primary and induced pluripotent stem cell (iPSCs)-derived vascular smooth muscle cells (VSMCs) from human subjects. Betaine was then examined in in vivo models for its geroprotective effects on Drosophila melanogaster (D. melanogaster) and Caenorhabditis elegans (C. elegans).

Results: Our data indicate that betaine is a potent senotherapeutic able to extend primary VSMCs life span and diminish expression of biomarkers of cellular senescence (p16, p21, Nrf2, SerpineB2, cytoplasmic chromatin fragments), and the senescence-associated pro-inflammatory secretome (IL1β, IL6), as well as biomarkers of VMSCs damage (FOXO4, LMNA). In iPSCs-induced VSMCs, betaine has also displayed potential geroprotective effects by downregulating vascular calcification, extracellular vesicles and oxidative damage. Additionally, it increased total mitochondria content while protecting mitochondria membrane potential against DMSO treatment. Our vivo models (C. elegans, D. melanogaster) exhibited up to 20% lifespan extension after supplementation with betaine.

Conclusion: Our data indicate that betaine may be a powerful naturally occurring senotherapy and suitable for safe future clinical development.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Supported by funding from the European Union and Marie Skłodowska-Curie Actions.
• Subjects: Q Science > QH Natural history > QH345 Biochemistry
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Funder's Name: European Union, Marie Skłodowska-Curie Actions
• Supervisor's Name: Shiels, Professor Paul
• Date of Award: 2025
• Depositing User: Theses Team
• Unique ID: glathesis:2025-85334
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 14 Jul 2025 09:29
• Last Modified: 15 Jul 2025 08:29
• Thesis DOI: 10.5525/gla.thesis.85334
• URI: https://theses.gla.ac.uk/id/eprint/85334

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