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Pflugers Archiv : European journal of physiology2022; 474(11); 1159-1169; doi: 10.1007/s00424-022-02745-0

Exercise regulates shelterin genes and microRNAs implicated in ageing in Thoroughbred horses.

Abstract: Ageing causes a gradual deterioration of bodily functions and telomere degradation. Excessive telomere shortening leads to cellular senescence and decreases tissue vitality. Six proteins, called shelterin, protect telomere integrity and control telomere length through telomerase-dependent mechanisms. Exercise training appears to maintain telomeres in certain somatic cells, although the underlying molecular mechanisms are incompletely understood. Here, we examined the influence of a single bout of vigorous exercise training on leukocyte telomerase reverse transcriptase (TERT) and shelterin gene expression, and the abundance of three microRNAs (miRNAs) implicated in biological ageing (miRNA-143, -223 and -486-5p) in an elite athlete and large animal model, Thoroughbred horses. Gene and miRNA expression were analysed using primer-based and TaqMan Assay qPCR. Leukocyte TRF1, TRF2 and POT1 expression were all significantly increased whilst miR-223 and miR-486-5p were decreased immediately after vigorous exercise (all p < 0.05), and tended to return to baseline levels 24 h after training. Relative to the young horses (~ 3.9 years old), middle-aged horses (~ 14.8 years old) exhibited reduced leukocyte TERT gene expression, and increased POT1 and miR-223 abundance (all p < 0.05). These data demonstrate that genes transcribing key components of the shelterin-telomere complex are influenced by ageing and dynamically regulated by a single bout of vigorous exercise in a large, athletic mammal - Thoroughbred horses. Our findings also implicate TERT and shelterin gene transcripts as potential targets of miR-223 and miR-486-5p, which are modulated by exercise and may have a role in the telomere maintenance and genomic stability associated with long-term aerobic training.
© 2022. The Author(s).
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Publication Date: 2022-09-09 PubMed ID: 36085194PubMed Central: PMC9560944DOI: 10.1007/s00424-022-02745-0Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research investigates how vigorous exercise affects certain genes and microRNAs that are linked to aging in thoroughbred horses. The study sheds light on the ways in which exercise might help maintain telomere length and cellular vitality, and thus contribute to delaying the aging process.

Introduction to Telomeres, Shelterin Proteins, and MicroRNAs

  • Ageing involves gradual wear and tear of body functions and degradation of telomeres, which are DNA-protein structures that protect the ends of chromosomes. When telomeres shorten excessively, it results in cellular aging and decreased tissue vitality.
  • Shelterin is a complex of six proteins that protect the integrity and length of telomeres through mechanisms dependent on an enzyme called telomerase.
  • MicroRNAs (miRNAs) are small RNA molecules associated with biological aging. They regulate gene expression and help control cellular processes.

Study Focus-Exercise and Telomere Maintenance

  • The research focuses on the influence of vigorous exercise training on the expression of shelterin gene and telomerase reverse transcriptase (TERT). Also targeted were three specific miRNAs (miRNA-143, miRNA-223 and miRNA-486-5p) known to be involved in aging.
  • The study was conducted among Thoroughbred horses, as an athletic mammal model. This involved analyses of gene and miRNA expressions using primer-based and TaqMan Assay qPCR techniques.

Noteworthy Findings

  • Increased expression of shelterin were noted in the horse’s leukocytes (white blood cells) immediately after they engaged in vigorous exercise.
  • The concentrations of miR-223 and miR-486-5p were found to be significantly lower directly after exercise.
  • Around 24 hours after training, the levels of shelterin and miRNAs started trending back towards their baseline pre-exercise levels.
  • In comparison to younger horses, the middle-aged ones exhibited lower TERT gene expression and higher amounts of POT1 (a shelterin component) and miR-223.

Implications and Conclusion

  • Results indicate that genes associated with the shelterin-telomere complex are impacted both by aging and vigorous exercise.
  • The action of exercise may regulate key components of the shelterin-telomere complex, in part, through modulation of miR-223 and miR-486-5p molecules.
  • This provides insights regarding the potential role of miR-223 and miR-486-5p in genomic stability and telomere maintenance, via exercise, which could in turn influence the process of ageing.
  • Although the research is carried out in horses, the results could have implications for humans since the cellular ageing process is a shared biological mechanism.

Cite This Article

APA
Mandal S, Denham MM, Spencer SJ, Denham J. (2022). Exercise regulates shelterin genes and microRNAs implicated in ageing in Thoroughbred horses. Pflugers Arch, 474(11), 1159-1169. https://doi.org/10.1007/s00424-022-02745-0

Publication

Pflugers Archiv : European journal of physiology
ISSN: 1432-2013
NlmUniqueID: 0154720
Country: Germany
Language: English
Volume: 474
Issue: 11
Pages: 1159-1169

Researcher Affiliations

Mandal, Shama
  • School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia.
Denham, Michele M
  • Jubilee Stud, Freshwater Creek, Victoria, Australia.
Spencer, Sarah J
  • School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia.
  • ARC Centre of Excellence for Nanoscale Biophotonics, RMIT University, Melbourne, VIC, Australia.
Denham, Joshua
  • School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia. josh.denham@usq.edu.au.
  • School of Health and Medical Sciences, University of Southern Queensland, Ipswich, QLD, 4305, Australia. josh.denham@usq.edu.au.
  • School of Science and Technology, University of New England, Armidale, NSW, Australia. josh.denham@usq.edu.au.

MeSH Terms

  • Aging / genetics
  • Animals
  • Horses / genetics
  • Mammals / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Shelterin Complex
  • Telomerase / genetics
  • Telomerase / metabolism
  • Telomere / genetics
  • Telomere / metabolism

Conflict of Interest Statement

M. D. owns and operates a Thoroughbred horse stud.

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