Hematopoietic stem cells and aging
Hematopoietic stem cells are not immune to the effects of aging, and they lose functionality as they age, which contributes to the risk of serious diseases such as blood cancers. The risk of developing age-related diseases varies among people, but little is known about whether hematopoietic stem cells age differently between people as well.
“If you take a room full of 50-year-olds, some will be completely gray-haired, others will be salt-and-pepper, and a few will not have any gray hairs at all,” said Jennifer Trowbridge, Dattels Family Endowed Chair and professor at the Jackson Laboratory. “Logically, you’d expect to see the same kind of variation in the function of hematopoietic stem cells — but until now, nobody has studied that directly.”
One of the reasons this hasn’t been explored more is because hematopoietic stem cells are rare. Typically all of these stem cells are pooled together to study in aggregate. This study, published in Blood, studied hematopoietic stem cells at the single-cell level in nine individual genetically identical middle-aged mice to examine how subtle changes in the bone marrow microenvironment may age hematopoietic stem cells across the individual mice.
What they found
The researchers found that despite the mice being the same age the hematopoietic stem cells in the bone marrow of the individual mice aged differently. To add to this the researchers were able to predict the function of the hematopoietic stem cells based on the activity of two growth factors that are present in humans.
Kitl and Igf1 growth factors are produced by mesenchymal stromal cells (MSC) which surround the stem cells within the bone marrow. Profiling RNA transcriptome in the MSCs across the individual mice reveals that the decline of these two growth factors correlated with age-associated molecular programs in the hematopoietic stem cells.
“The amount of the growth factors that are being produced directly correlates to the declining function of the stem cells — and we found markedly more variation in hematopoietic stem cells than in other cells in the bone marrow,” Trowbridge said. “This is really a snapshot of the aging process at work, at the cellular level.”
In humans who are genetically diverse and have varying lifestyles, the variations in hematopoietic stem cell aging are likely to be even greater than observed in the carefully controlled animal models used in this study.
According to the researchers, this study did not examine whether cellular aging of the stem cells directly triggers adverse health outcomes, but it is likely that variations play a role in a variety of outcomes from both mice and humans.
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Image: The immunofluorescence image details the morphology and cell composition of a femur from a middle-aged mouse. Credit: Jennifer Trowbridge
https://www.jax.org/news-and-insights/2024/june/how-old-is-your-bone-marrow
