Changes in DNA methylation patterns and repetitive sequences in blood lymphocytes of aged horses.
Abstract: It is known that aged organisms have modified epigenomes. Epigenetic modifications, such as changes in global and locus-specific DNA methylation, and histone modifications are suspected to play an important role in cancer development and aging. In the present study, with the well-established horse aging model, we showed the global loss of DNA methylation in blood lymphocytes during juvenile-to-aged period. Additionally, we tested a pattern of DNA methylation of ribosomal DNA and selected genes such as IGF2 and found no significant changes during development and aging. We asked if genetic components such as polymorphisms within DNA methyltransferase genes, DNMT1, DNMT3a, and DNMT3b, may contribute to observed changes in global DNA methylation status. The analysis of seven intragenic polymorphisms did not reveal any significant association with changes in global DNA methylation. Telomere shortage and a loss of pericentromeric heterochromatin during juvenile-to-aged period were also observed. Transcriptional rDNA activity, assessed as the number and size of nucleolar organizer regions, reflecting physiological state of the cell, and mitotic index were decreased with increasing horse donor age. Moreover, changes during juvenile-to-aged period and adult-to-aged period were compared and discussed. Taken together, changes in global DNA methylation status originating in development and affecting the stability of repetitive sequences may be associated with previously reported genomic instability during horse aging.
Publication Date: 2013-05-23 PubMed ID: 23700175PubMed Central: PMC3889908DOI: 10.1007/s11357-013-9541-zGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
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.
The study explores the changes in DNA methylation patterns and repetitive sequences in the blood lymphocytes of aging horses. The researchers observed a global loss of DNA methylation (a molecular process that helps regulate gene activity) during the juvenile-to-aged period, potentially contributing to genomic instability during horse aging.
Key Findings
- In the study, the researchers detected a global loss of DNA methylation in blood lymphocytes as horses age from the juvenile to aged stage. DNA methylation, a key epigenetic modification, is crucial for the functionality and regulation of our genome. It generally acts to repress gene transcription and can play a role in phenomena like inactivation of the X chromosome, cancer, and aging.
- They evaluated the DNA methylation patterns of ribosomal DNA and certain genes like IGF2. However, they did not find any significant changes in the methylation pattern of these genes during development and aging.
Molecular and Cellular Impact
- The researchers investigated whether genetic factors such as polymorphisms (variations) within specific DNA methyltransferase genes (DNMT1, DNMT3a, and DNMT3b), which are responsible for adding methyl groups to DNA, contribute to changes in global DNA methylation. No significant association was found.
- The team observed telomere shortening and a loss of pericentromeric heterochromatin (a tightly packed form of DNA) during the juvenile-to-aged transition. Both of these changes could affect the stability of chromosomes and impact cellular function.
- They also observed a decrease in transcriptional rDNA activity, as demonstrated by a declining number and size of nucleolar organizer regions. These changes reflect the physiological state of the cell and the researchers found that they lessened as the horse’s donor age increased.
Horse Aging Model
- The study showed distinctions in the changes observed during the juvenile-to-aged period and the adult-to-aged period, suggesting that aging impacts may vary over the lifespan.
- Overall, the researchers concluded that alterations in global DNA methylation, arising from changes during development, can impact the stability of repetitive sequences and could potentially be associated with previously reported genomic instability during horse aging.
The study adds to our understanding of aging processes, providing insights that may help in understanding the fundamental biological changes as organisms age. However, more research is needed to further explore these mechanisms and implications for other species, including humans.
Cite This Article
APA
Wnuk M, Lewinska A, Gurgul A, Zabek T, Potocki L, Oklejewicz B, Bugno-Poniewierska M, Wegrzyn M, Slota E.
(2013).
Changes in DNA methylation patterns and repetitive sequences in blood lymphocytes of aged horses.
Age (Dordr), 36(1), 31-48.
https://doi.org/10.1007/s11357-013-9541-z Publication
Researcher Affiliations
- Department of Genetics, University of Rzeszów, Rejtana 16C, PL 35-959, Rzeszów, Poland, mawnuk@gmail.com.
MeSH Terms
- Age Factors
- Animals
- Antigens, Nuclear / genetics
- Blotting, Southern
- Cell Culture Techniques
- Chromatography, High Pressure Liquid
- Chromosome Banding
- CpG Islands / genetics
- DNA (Cytosine-5-)-Methyltransferases / genetics
- DNA Methylation
- DNA Methyltransferase 3A
- DNA Modification Methylases / genetics
- DNA Primers
- Epigenomics
- Gene Expression
- Genotype
- Horses
- Insulin-Like Growth Factor II / genetics
- Lymphocytes / chemistry
- Lymphocytes / enzymology
- Mitotic Index
- Polymerase Chain Reaction
- Polymorphism, Genetic
- Repetitive Sequences, Nucleic Acid / genetics
- Telomere Shortening
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