Topic: Biology

Researchers at Icahn School of Medicine at Mount Sinai reversed aging in blood stem cells by repairing lysosomal defects. This breakthrough could help improve immune defenses and reduce cancer risk.

Blood stem cells are crucial for our body's ability to regenerate blood and immune cells. As we age, these stem cells gradually lose their ability to repair and replenish the blood system. This decline weakens our immune defenses and contributes to increased vulnerability to infections in older adults.

Scientists at Icahn School of Medicine at Mount Sinai have successfully reversed aging in blood-forming stem cells in mice by repairing defects in structures known as lysosomes. Lysosomes are like the cell's internal recycling centers, breaking down proteins, nucleic acids, carbohydrates, and lipids to help cells dispose of waste and reuse materials.

The research team focused on hematopoietic stem cells (HSCs), which generate all blood and immune cells in the body. As people grow older, these stem cells gradually lose their ability to repair and replenish the blood system. This decline weakens immune defenses and contributes to increased vulnerability to infections seen in older adults.

The study was led by Saghi Ghaffari, MD, PhD, Professor of Cell, Developmental, and Regenerative Biology at the Icahn School of Medicine and a member of the Black Family Stem Cell Institute. The research team found that lysosomes in aged HSCs become excessively acidic, damaged, depleted, and abnormally active.

Using single-cell transcriptomics and functional testing, the team found that blocking this excessive lysosomal activity with a vacuolar ATPase inhibitor restored lysosomal health and improved the function of aging blood stem cells. After treatment, the old stem cells began behaving more like young, healthy cells again.

The treated cells also showed improved metabolism and mitochondrial performance, healthier epigenetic patterns, reduced inflammation, and fewer harmful inflammatory signals that can damage tissues throughout the body.

Why It Matters

This breakthrough has significant implications for older adults who are more vulnerable to infections. It could lead to new treatments that improve immune defenses and reduce cancer risk.

Key Facts

• Researchers at Icahn School of Medicine at Mount Sinai reversed aging in blood stem cells by repairing lysosomal defects.
• Lysosomes are like the cell's internal recycling centers, breaking down proteins, nucleic acids, carbohydrates, and lipids to help cells dispose of waste and reuse materials.
• The study was led by Saghi Ghaffari, MD, PhD, Professor of Cell, Developmental, and Regenerative Biology at the Icahn School of Medicine and a member of the Black Family Stem Cell Institute.
• Blocking excessive lysosomal activity with a vacuolar ATPase inhibitor restored lysosomal health and improved the function of aging blood stem cells.
• The treated cells showed improved metabolism, mitochondrial performance, healthier epigenetic patterns, reduced inflammation, and fewer harmful inflammatory signals.

Key Terms

Lysosomes

Structures that break down proteins, nucleic acids, carbohydrates, and lipids to help cells dispose of waste and reuse materials

Implications

This breakthrough has significant implications for older adults who are more vulnerable to infections. It could lead to new treatments that improve immune defenses and reduce cancer risk.