In this week's Science, Whitehead Institute researchers publish the results of a CRISPR-Cas9 screen identifying the protein sideroflexin 1 as a requisite component of one-carbon metabolism — a process in which the amino acid serine is used by the cell to generate one-carbon units required for metabolite synthesis. The screen was designed to find genes related to serine transport and identified sideroflexin 1 as the main mitochondrial serine transporters in human cells. Further experimentation showed that cells lacking sideroflexin 1 are defective in glycine and purine synthesis, while cells lacking the protein and one of its homologs have even more severe defects.
And in Science Translational Medicine, a team led by scientists from the National Institute on Aging reports data showing that a decline in beneficial gut bacteria contributes to aging-associated insulin resistance. The researchers sequenced the fecal microbiome of young and aged mice, and found that the older rodents had lower levels of the beneficial bacteria species Akkermansia muciniphila. This deficit contributed to the impairment of intestinal integrity, resulting in the leakage of bacterial products that — in combination with lower levels of the fatty acid butyrate — promoted monocytes to convert B cells into pro-inflammatory 4BL cells and increase insulin resistance. Notably, the investigators were able to restore normal insulin response in aged mice or monkeys by treating the animals with either butyrate or an antibiotic that boosted A. muciniphila levels.