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Scientists Reverse Aging Blood Stem Cells Through Cellular Cleanup

Researchers at the Icahn School of Medicine at Mount Sinai reversed aging in mouse hematopoietic stem cells by correcting lysosomal defects, showing restored slow degradation revitalizes aged HSCs, the study in Cell Stem Cell reports.
Lysosomes act as the cell's recycling system, breaking down biomolecules and storing nutrients, and Saghi Ghaffari, MD, PhD's team focused on hematopoietic stem cells that generate blood and immune cells.
Using single-cell transcriptomics, the team discovered aged HSC lysosomes were hyper-acidic and damaged, and vacuolar ATPase inhibitor treatment restored lysosomal integrity, boosting blood-forming capacity over eightfold while reducing cGAS-STING activation.
Old stem cells regained youthful function, renewing metabolism, mitochondrial activity, and epigenetic stability while reducing inflammation; targeting this pathway may aid older patients in stem cell transplants and gene therapy conditioning.
Supported by NIH and other funders, Ghaffari's team is investigating whether lysosomal defects in aged stem cells may contribute to leukemic stem cell formation, in collaboration with the Imagine Institute in Paris.

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Scientists reverse aging in blood stem cells by targeting lysosomal dysfunction

Researchers at the Icahn School of Medicine at Mount Sinai have discovered how to reverse aging in blood-forming stem cells in mice by correcting defects in the stem cell's lysosomes. The breakthrough, published in Cell Stem Cell, identifies lysosomal hyperactivation and dysfunction as key drivers of stem cell aging and shows that restoring lysosomal slow degradation can revitalize aged stem cells and enhance their regenerative capacity.

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