To Ward Off Aging, Stem Cells Must Take Out the Trash

In humanity’s ongoing quest for the elixir of life, the science keeps pointing to stem cells. Research increasingly shows that maintaining stem cell fitness promotes a long healthspan, and new findings show keeping stem cells clean and tidy is an integral step.

In a study published March 21, 2023 in Cell Stem Cell, researchers at University of California San Diego School of Medicine found that blood stem cells use an unexpected method to get rid of their misfolded proteins, and that this pathway’s activity degrades with age. The authors say boosting this specialized garbage disposal system could help protect against age-related diseases.

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The study focused on hematopoietic stem cells (HSCs), the cells in our bone marrow that produce new blood and immune cells throughout our lives. When their function is weakened or lost, this can lead to blood and immune disorders, such as anemia, blood clotting and cancer.

“Stem cells are in it for the long haul,” said senior study author Robert Signer, PhD, associate professor at UC San Diego School of Medicine. “Their need for longevity requires them to be wired differently than all the short-lived cells in the body.”

A key to keeping stem cells happy is maintaining protein homeostasis. Previous work showed that stem cells, including HSCs, synthesize proteins much slower than other cell types, prioritizing quality over quantity. This helps them make fewer mistakes in the process, as misfolded proteins can become toxic to cells if allowed to build up.

Still, some mistakes or protein damage are inevitable, so the researchers set out to understand how stem cells ensure these proteins are properly discarded.

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