Researchers have discovered that specific antioxidant enzymes known as selenoproteins play a crucial role in combatting cellular aging. The research team utilized a gene knockout mouse model to explore the consequences of disrupting the production of selenoproteins. This disruption adversely affected hematopoietic stem cells and immune cells of the B cell lineage, primarily due to the inability to counteract lipid peroxides, highlighting the significance of selenoproteins in age-related diseases.
Numerous foods are promoted for their antioxidant benefits. Antioxidants help neutralize reactive oxygen species (ROS), which are chemically reactive molecules that can interfere with the proper functioning of lipids, proteins, and DNA in human cells. The buildup of ROS is linked to the onset of age-related illnesses, including cancer, making it essential to maintain a balanced oxidant and antioxidant level. A recent article in Blood, authored by researchers from Osaka University and other Japanese institutions, outlines the vital antioxidant role of selenoproteins and the effects of disrupting their production on various cell types, particularly in the process of blood cell formation, known as hematopoiesis.
The human body produces 25 distinct selenoproteins. These antioxidant enzymes are responsible for converting harmful ROS, like lipid peroxides, into safer substances. An accumulation of lipid peroxides can harm important hematopoietic stem cells (HSCs), a situation commonly seen in age-related diseases.
“We found that aged HSCs often show reduced selenoprotein synthesis, but the implications for cellular aging and potential reversibility were unclear,” explains Yumi Aoyama, the study’s co-lead author. “We believed that selenoproteins are essential to the antioxidant system that combats age-related changes in HSCs.”
To explore this hypothesis, the team employed a genetically modified mouse model lacking a gene that is vital for selenoprotein production. Their findings revealed that this genetic alteration negatively impacted HSCs and B cell lineage immune cells (a type of white blood cell) while having minimal effects on myeloid cells (another category of immune cells).
“Among the most significant outcomes of the gene knockout was a condition known as B lymphocytopenia, characterized by a reduced number of B cells,” says Hiromi Yamazaki, the other co-lead author. “Additionally, HSCs exhibited a decreased capacity for self-renewal.”
These findings, coupled with elevated levels of aging-related gene expression in the affected cell types, aligned with patterns often seen in age-related disorders. Further research indicated that these effects stemmed from lipid peroxidation. Experiments involving cells from the knockout model also suggested that the disruption in selenoprotein synthesis could facilitate B progenitors’ transition to the myeloid lineage.
“Our results indicate distinct lineage-specific consequences following the loss of the protective functions of selenoproteins,” says Daichi Inoue, the study’s senior author. “These enzymes are vital for neutralizing the lipid peroxides that accumulate as we age.”
The researchers also delved into the mechanisms of hematopoiesis by conducting a feeding experiment on the knockout mice. They discovered that dietary Vitamin E could safeguard hematopoiesis and restore impaired B cell differentiation.
This investigation highlights the antioxidant roles of selenoproteins and their necessity for proper self-renewal of HSCs and maturation of B cell lineage immune cells. Since the knockout mice demonstrated similar traits to aged normal mice, the results underline the potential of addressing selenoprotein-related issues in combating age-associated diseases.
