Aging impairs peroxisome biogenesis in human B cells.

Emerging evidence highlights the critical role of cellular metabolism in immune cell activation, development, and function. Peroxisomes, key metabolic organelles, maintain metabolic homeostasis, yet their role in immune cells remains underexplored. While animal studies show age-related declines in peroxisome biogenesis, this process is unconfirmed in human aging. We investigated peroxisome biogenesis in human peripheral blood mononuclear cells (PBMCs) and found a significant decline in aged CD19+ B cells compared to CD4+ T cells, CD8+ T cells, and CD14+ monocytes. B cell aging also reduces peroxisomal matrix enzyme import, evidenced by decreased SKL-containing enzymes and mature ACOX1, alongside downregulation of PEX19 and E3 ubiquitin ligases PEX2, PEX10, and PEX12. These findings confirm an evolutionarily conserved and age-related decline in peroxisome biogenesis. Further, our work unveils cell type-specific changes in aging human PBMCs, and provides new insights into peroxisome-mediated immunometabolism and B cell aging.