Scientists Found a Way to Make Old Blood Young Again

3 min read

Here’s what you’ll learn when you read this story:

• Lysosomes, organelles found in all animal cells, act as a kind of cellular “stomach” for waste disposal while also serving as the mediator of apoptosis, a cell’s last line of defense against infection.
• A new study analyzed lysosomes in aged hematopoietic (blood-forming) stem cells and found that as we age, these organelles become “abnormally active,” turning acidic and eventually becoming damaged and depleted.
• By inhibiting this overactivity, scientists returned cells to a younger state, suggesting that treating lysosomes could help prevent blood cancers and inflammation as we age.

According to the old saying, you can’t teach an old dog new tricks, but recent research suggests that adage may not hold up for hematopoietic stem cells, or HSCs.

In a new study published in the journal Cell Stem Cell, scientists at the Icahn School of Medicine at Mount Sinai in New York focused specifically on lysosomes located within the stem cells themselves. These spherical organelles come with a couple of amazing nicknames. The first is “the stomach,” reflecting the fact that the organelle uses upwards of 50 kinds of hydrolytic enzymes for cell maintenance and waste disposal. The second (and most metal nickname) is “suicide bags,” since lysosomes also mediate apoptosis, intentionally killing off a cell to keep a viral or bacterial infection from spreading.

In other words, lysosomes are an immensely important part of all animal cells, but when they age, lysosomes become a liability. By analyzing HSCs—rare, long-lasting stem cells found in bone marrow that generate blood and immune cells—scientists could see the effects of these aged cells in the body. As we age, these cells lose their ability to repair the blood system, which can lead to a variety of blood illnesses, including cancers and inflammation. The team found that this dysfunction can be linked to lysosomes, which become abnormally active, growing excessively acidic and ultimately damaging and depleting the cells.

Using single-cell transcriptomics and ex vivo testing, researchers successfully blocked this overactivity using a vacuolar ATPase inhibitor. The results were stunning, effectively transforming the aged HSC into a young, healthy version of itself.

“Old blood stem cells have the capacity to revert to a youthful state; they can bounce back,” Icahn School of Medicine’s Saghi Ghaffari, senior author of the study, said in a press statement. “By targeting lysosomal hyperactivity, we were able to reset aged stem cells to a younger, healthier state, improving their ability to regenerate blood and immune cells.”

In further experiments, Ghaffari and her team tested the inhibitor in cell cultures and found that aged HSCs increased their blood-forming ability by a factor of eight while reducing inflammation. These “younger” stem cells could more easily process mitochondrial DNA and—crucially—lower the activation of an immune signaling pathway that’s central to aged-based inflammation.

HSCs are particularly useful for anti-aging therapies, and in a study published in August last year, scientists revealed how HSCs have a tendency to migrate to the skin and aid in homeostasis. Amazingly, they can also take years off a skin cell’s biological age when exposed to bone marrow cells from younger donors, likely due to specific proteins that support rejuvenation. Studies have also investigated whether HSCs could ward off deadly cancers, such as leukemia. The authors of this new study hope to investigate ways that malfunctioning lysosomes could contribute to the creation of leukemic stem cells.

“Targeting this pathway may one day help maintain healthy blood and immune systems in the elderly, improve their stem cells for transplantation, and reduce the risk of age-associated blood disorders and perhaps have an effect on overall aging,” Ghaffri says.