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Open AccessArticle

The Cbs Locus Affects the Expression of Senescence Markers and mtDNA Copy Number, but not Telomere Dynamics in Mice

1
Department of Biochemistry and Biotechnology, University of Life Sciences, 60-632 Poznań, Poland
2
Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznań, Poland
3
Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers-New Jersey Medical School, International Center for Public Health, Newark, NJ 07-103, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(7), 2520; https://doi.org/10.3390/ijms21072520
Received: 4 January 2020 / Revised: 13 March 2020 / Accepted: 1 April 2020 / Published: 5 April 2020
(This article belongs to the Special Issue Targeting Mitochondria in Aging and Disease)
Cystathionine β-synthase (CBS) is a housekeeping enzyme that catalyzes the first step of the homocysteine to cysteine transsulfuration pathway. Homozygous deletion of the Cbs gene in mice causes severe hyperhomocysteinemia and reduces life span. Here, we examined a possible involvement of senescence, mitochondrial DNA, and telomeres in the reduced life span of Cbs−/− mice. We found that senescence-related p21, Pai-1, Mcp1, and Il-6 mRNAs were significantly upregulated (2–10-fold) in liver, while p21 was upregulated in the brain of Cbs−/− mice (n = 20) compared with control Cbs+/− siblings (n = 20) in a sex- and age-dependent manner. Telomere length in blood (n = 80), liver (n = 40), and brain (n = 40) was not affected by the Cbs−/− genotype, but varied with sex and/or age. Levels of mitochondrial DNA tended to be reduced in livers, but not brains and blood, of Cbs−/− females (n = 20–40). The Cbs−/− genotype significantly reduced Tert mRNA expression in brain, but not liver, in a sex- and age-dependent manner. Multiple regression analysis showed that the senescence-related liver (but not brain) mRNAs and liver (but not brain or blood) mitochondrial DNA were associated with the Cbs genotype. In contrast, telomere length in blood, brain, and liver was not associated with the Cbs genotype or hyperhomocysteinemia, but was associated with sex (in brain and liver) and age (in brain and blood). Taken together, these findings suggest that the changes in senescence marker expression and mtDNA levels, but not telomere shortening, could account for the reduced life span of Cbs−/− mice. View Full-Text
Keywords: cystathionine β-synthase deficiency; homocysteine; life span; mtDNA; senescence markers; telomere dynamics; Tert cystathionine β-synthase deficiency; homocysteine; life span; mtDNA; senescence markers; telomere dynamics; Tert
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MDPI and ACS Style

Utyro, O.; Perła-Kaján, J.; Jakubowski, H. The Cbs Locus Affects the Expression of Senescence Markers and mtDNA Copy Number, but not Telomere Dynamics in Mice. Int. J. Mol. Sci. 2020, 21, 2520. https://doi.org/10.3390/ijms21072520

AMA Style

Utyro O, Perła-Kaján J, Jakubowski H. The Cbs Locus Affects the Expression of Senescence Markers and mtDNA Copy Number, but not Telomere Dynamics in Mice. International Journal of Molecular Sciences. 2020; 21(7):2520. https://doi.org/10.3390/ijms21072520

Chicago/Turabian Style

Utyro, Olga; Perła-Kaján, Joanna; Jakubowski, Hieronim. 2020. "The Cbs Locus Affects the Expression of Senescence Markers and mtDNA Copy Number, but not Telomere Dynamics in Mice" Int. J. Mol. Sci. 21, no. 7: 2520. https://doi.org/10.3390/ijms21072520

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