Selenoproteins: The fountain of youth?

Human cells have 25 different selenoproteins. These antioxidant enzymes help convert dangerous ROS, such as lipid peroxides, into a safer form. Buildup of lipid peroxides can affect critical cells called hematopoietic stem cells (HSCs), a phenomenon observed in aging diseases.

"We observed that aged HSCs frequently display impaired selenoprotein synthesis, but it was unclear how this could contribute to cell aging and if it could be reversed," says Yumi Aoyama, co-lead author of the study. "We hypothesized that selenoproteins are a critical part of the antioxidant system that fights age-related changes in HSCs."

To investigate this, the team used a mouse model with a certain gene knocked out, leading to disrupted selenoprotein production. They then examined how this affected different cell types, finding that the knockout negatively impacted HSCs and immune cells with B cell lineage (types of white blood cells) but had few effects on myeloid cells (a different family of immune cells).

"The most notable results of the knockout included B lymphocytopenia, which means there were fewer B cells than expected," explains Hiromi Yamazaki, the other co-lead author. "The HSCs also had a limited ability to self-renew."

These observations, along with increased expression levels of aging-related genes in these cell types, were consistent with what is frequently seen in age-related diseases. Further investigation indicated that the effects were driven by lipid peroxidation. Additionally, experiments with cells from the mouse model revealed that the disruption in selenoprotein synthesis could support B progenitors switching to the myeloid cell family.

"Our data suggest clear lineage-specific effects when the protective role of selenoproteins is lost," says Daichi Inoue, senior author of the study. "These enzymes are critical for counteracting the lipid peroxides that accumulate during the aging process."

The researchers also investigated the mechanisms underlying hematopoiesis with a feeding experiment on the knockout mice. They revealed that dietary Vitamin E can protect hematopoiesis and has the ability to repair impaired B cell differentiation.

This study shows the antioxidant functions of selenoproteins and how they ensure proper HSC self-renewal and B cell-lineage immune cell maturation. Because the knockout mice displayed similar phenotypes to aged normal mice, the findings demonstrate how potentially addressing selenoprotein production-related issues could help fight age-related diseases.