A new study shows that the expansion in size of stem cells contributes to age-related functional decline. Researchers discovered that blood stem cells – the smallest cells in the body, lose the ability to perform their normal functions – replenish the body with blood cells, as they grow larger.
Scientists at the Massachusetts Institute of Technology (MIT) have an answer to an important question: Why do cells control their size?
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Cells of the same type are relatively uniform in size, whereas cell size varies between different cell types. This raises the question of whether cell size is important for cell physiology?
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This study shows that size expansion leads to impaired stem cell function. Researchers discovered that blood stem cells (one of the smallest cells in the body) lose their normal ability (to add new blood cells to the body), as they grow. bigger. However, when they return to their normal size, they will function normally again.
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Researchers also found that blood stem cells tend to enlarge as they age. This suggests that this size expansion contributes to stem cell decline during aging.
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“We have discovered cell hypertrophy as a new aging factor and now can we discover how to treat cell hypertrophy to delay aging and related diseases? to aging or not? Jette Lengefeld, a former postdoctoral researcher at MIT, is now a principal investigator at the University of Helsinki.
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Lengefeld is the lead author of the study, which appears in the journal Science Advances. Angelika Amon, a late professor of biology at MIT and a member of the Koch Institute for Integrative Oncology, is senior author of the study.
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EFFECTS OF OVERSIZE
Since the 1960s, we have known that human cells grown in lab dishes enlarge as they age, in a non-dividing state that is associated with the aging process. Every time cells divide, they can encounter DNA damage. When this happens, the division process will pause to repair the damage. During the delay, the cell will grow slightly larger. Many scientists believe that this enlargement is simply a side effect of the aging process. But Amon's lab began investigating the possibility that large cell sizes lead to loss of function with aging.
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Lengefeld studied the size of stem cells, specifically blood stem cells – which create the body's blood cells throughout life. To study how size affects stem cells, researchers caused damage to their DNA, resulting in an increase in size. They then compared these increased cells with cells that also had DNA damage but were prevented from increasing in size using a drug, called ramamycin.
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The researchers then tested the function of these two groups of cells by injecting them into mice that had had blood stem cells removed. This allowed the researchers to determine whether the transplanted stem cells could regenerate the mice's blood cells.
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They discovered that processed and enlarged blood stem cells were unable to form new blood. However, blood stem cells are kept the same size and still have the ability to create new blood cells.
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In another experiment, the researchers used a genetic mutation that reduces the size of naturally increased stem cells found in aged mice. They discovered that if they made those stem cells smaller, they regained their regenerative potential and behaved like younger stem cells.
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“This would be outstanding evidence supporting the model that size is important for stem cell function,” Lengefeld said. “When we cause damage to the DNA of stem cells that remain small during the damage, they retain their function. And if we reduce the size of large cells, we can restore their function."
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MAINTAINS SMALL CELLS
When researchers treated mice with rapamycin, starting at an early age, they were able to prevent blood stem cells from expanding as the mice aged. Blood stem cells from those mice could still produce the same blood cells as young blood stem cells, even when they were 3 years old – quite old for a mouse.
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Rapamycin, a drug that can inhibit cell growth, is currently used to treat certain cancers and prevent organ transplant rejection, and it has attracted attention for its ability to prolong life. in mice and other organisms. It may be useful in slowing the growth of stem cells and thus it may have beneficial effects in humans. Lengefeld said:
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“If we find drugs that specifically shrink large blood stem cells, we can test whether this improves the health of people with blood system problems such as anemia. and immune system impairment or may even help people with leukemia.”
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Researchers have also demonstrated the importance of size in another type of stem cell – intestinal stem cells. They found that larger stem cells were less able to produce intestinal organoids, which mimic the structure of the intestinal lining in a test tube.
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"This shows that the relationship between size and function is conserved in stem cells, and that cell size is a marker of stem cell function," Lengefeld stated.
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The study was funded in part by the Howard Hughes Medical Institute, the Jane Coffin Children's Memorial Fund, the Swiss National Science Foundation, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Koch (primarily) from the National Cancer Institute and the MIT Stem Cell Initiative.
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Translator: Thanh Long - Phacogen Institute of Technology
Bachelor of Biotechnology - University of Natural Sciences - Hanoi National University
Referral:
Jette Lengefeld, Chia-Wei Cheng, Pema Maretich, Marguerite Blair, Hannah Hagen, Melanie R. McReynolds, Emily Sullivan, Kyra Majors, Christina Roberts, Joon Ho Kang, Joachim D. Steiner, Teemu P. Miettinen, Scott R. Manalis, Adam Antebi, Sean J. Morrison, Jacqueline A. Lees, Laurie A. Boyer, Ömer H. Yilmaz, Angelika Amon. Cell size is a determinant of stem cell potential during aging. Science Advances, 2021; 7 (46) DOI: 10.1126/sciadv.abk0271.
Source of article: https://www.sciencedaily.com/releases/2021/11/211113072504.htm.
