Selenoprotein Antioxidants Decline with Age in Hematopoietic Stem Cells
Researchers here provide some initial evidence for declining expression of a network of natural antioxidant molecules known as selenoproteins to contribute to the aging of hematopoietic stem cells, responsible for generating red blood cells and immune cells. Note that the researchers impaired selenoprotein expression and observed impaired function, which is nowhere near as convincing as restoring lost expression to observe improved function. There are any number of ways to break cell function and produce results that look similar to aging, even though the specific breakage isn't all that relevant to normal aging. The next step for this line of research is to find a way to restore selenoprotein expression in aged mice, and look for improvement in hematopoiesis.
Human cells have 25 different selenoproteins. These antioxidant enzymes help convert dangerous reactive oxygen species (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. 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 tRNAsec 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). 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.