Longevity & AgingCRISPR Screen Pinpoints Clusterin as Master Driver of Immune Aging in Blood Stem Cells
As we age, blood stem cells (HSCs) progressively overproduce myeloid immune cells at the expense of lymphocytes, weakening adaptive immunity and raising disease risk. Researchers at Boston Children's Hospital and Harvard ran an in vivo CRISPR screen in aged mice to find which upregulated genes drive this bias. They identified clusterin (Clu) as a top culprit. Clu protein causes mitochondria to over-fuse, boosting oxidative phosphorylation and reactive oxygen species, which activates p38 MAPK signaling and raises the myeloid transcription factor C/EBPβ. Knocking out Clu in old HSCs restored balanced blood cell production and improved physical function in recipient mice, pointing to a druggable axis for reversing immune aging.
