Department of Biochemistry and Biotechnology, University of Life Sciences, 60-632 Poznań, Poland.
Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznań, Poland.
Int J Mol Sci. 2020 Apr 5;21(7):2520. doi: 10.3390/ijms21072520.
Cystathionine β-synthase (CBS) is a housekeeping enzyme that catalyzes the first step of the homocysteine to cysteine transsulfuration pathway. Homozygous deletion of the 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 mice. We found that senescence-related , , , and mRNAs were significantly upregulated (2-10-fold) in liver, while was upregulated in the brain of mice ( = 20) compared with control siblings ( = 20) in a sex- and age-dependent manner. Telomere length in blood ( = 80), liver ( = 40), and brain ( = 40) was not affected by the genotype, but varied with sex and/or age. Levels of mitochondrial DNA tended to be reduced in livers, but not brains and blood, of females ( = 20-40). The genotype significantly reduced 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 genotype. In contrast, telomere length in blood, brain, and liver was not associated with the 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 mice.
胱硫醚 β-合酶（CBS）是一种管家酶，催化同型半胱氨酸向半胱氨酸转硫途径的第一步。CBS 基因在小鼠中纯合缺失会导致严重的高同型半胱氨酸血症，并缩短寿命。在这里，我们研究了衰老、线粒体 DNA 和端粒在减少 CBS 基因缺失小鼠寿命中的可能作用。我们发现，衰老相关的 、 、 和 mRNA 在肝脏中显著上调（2-10 倍），而 在 基因缺失小鼠的大脑中上调（=20），与对照 同窝仔鼠（=20）相比，存在性别和年龄依赖性（=20）。血液（=80）、肝脏（=40）和大脑（=40）中的端粒长度不受 基因型影响，但受性别和/或年龄影响。线粒体 DNA 水平在雌性 基因缺失小鼠的肝脏中趋于降低，但在大脑和血液中没有降低（=20-40）。 基因型以性别和年龄依赖的方式显著降低大脑（但不是肝脏）中的 mRNA 表达。多元回归分析表明，肝脏（但不是大脑）中的衰老相关 mRNA 和肝脏（但不是大脑或血液）中的线粒体 DNA 与 基因型有关。相比之下，血液、大脑和肝脏中的端粒长度与 基因型或高同型半胱氨酸血症无关，但与性别（大脑和肝脏）和年龄（大脑和血液）有关。总之，这些发现表明衰老标志物表达和 mtDNA 水平的变化，但不是端粒缩短，可能导致 CBS 基因缺失小鼠寿命缩短。
