- Bone marrow contains stem cells that make the different types of blood cells needed for our immune system.
- The diversity of these blood cells declines with age, and this is thought to contribute to some aspects of aging.
- Chinese researchers transplanted bone marrow from young mice into older mice with Alzheimer's disease and found that the transplants reversed some of the signs of aging and the buildup of amyloid beta.
- The mice's cognitive abilities also improved.
A recent study showed that mice that received bone marrow transplants from young mice showed a reduction in many of the signs of brain aging.
Not only did their brains have lower levels of neurodegeneration, they also had less behavioral problems and lower levels of amyloid beta, a peptide that is a hallmark of Alzheimer's disease.
Researchers at the Third Military Medical University in Chongqing, China hypothesized that transplanting young hematopoietic stem cells – stem cells in the bone marrow that make different types of blood cells – into older mice could help stave off some of the signs of ageing.
Their results are Scientific advances.
The researchers decided to investigate this method.
Stem cells carrying proliferation-promoting mutations make up the majority of the stem cell population, resulting in reduced overall diversity.
This specifically affects the variety of immune cells the body is able to produce, and some researchers believe this may be one reason why older people are less able to stave off infections.
In this case, the researchers looked at the effects of bone marrow transplants on the brain and markers of Alzheimer's disease.
This is appropriate since Alzheimer's is a disease of aging. Rizwan Bashir, MD“We're a neurologist at Asia Orthopedic Surgery, who was not involved in the study,” Today's Medical News.
He explained:
“Alzheimer's disease is primarily a disease of aging, as it is closely linked to biological changes that occur with age. As we age, brain function naturally declines due to cellular damage, accumulation of oxidative stress, and reduced efficiency in removing metabolic waste products.”
“This progressive decline can lead to the accumulation of amyloid-beta plaques and tau tangles, which are hallmarks of Alzheimer's disease. Moreover, the brain's ability to repair itself decreases with age, making it more susceptible to neurodegenerative processes,” he continued.
To investigate the relationship between hematopoietic stem cell age and brain aging, and whether bone marrow transplants could restore hematopoietic stem cells, the researchers used 9- and 2-month-old mice that had been genetically engineered to model Alzheimer's disease.
The researchers split 9-month-old mice into two groups: one group received a bone marrow transplant from a 2-month-old mouse, and the control group received a bone marrow transplant from another 9-month-old mouse.
The researchers first compared gene expression in old and young mice and identified several age-related genes whose expression was either increased or decreased in the old mice.
Upregulated aging pathways identified in aged mice were generally associated with mitochondrial function, whereas downregulated aging pathways were generally associated with epigenetic regulation and immune processes.
Dysfunction in mitochondria, the so-called powerhouses of the cell, has been linked to Alzheimer's disease, as have certain epigenetic changes, which are alterations in gene expression caused by a person's environment and lifestyle factors.
Ultimately, the researchers found that expression of these genes was restored after bone marrow transplantation, with two types of immune cells most affected by the procedure: T cells and monocytes.
The researchers also compared the expression of the top 45 risk genes for Alzheimer's disease in different types of immune cells.
The researchers found that the top 10 genes for Alzheimer's disease risk were differentially expressed in a type of white blood cell called monocytes in old mice, and that bone marrow transplantation from young mice reversed these changes in expression.
Notably, bone marrow transplantation restored the ability of monocytes to clear amyloid-β deposits and reduced amyloid-β levels in the brain and plasma of 9-month-old mice transplanted with bone marrow from younger mice.
These mice also experienced reduced neuroinflammation (inflammation in the brain) and loss of neurons (brain cells). Additionally, cognition-related behaviors improved in the older mice that received bone marrow transplants.
Zachary Hervanek, MD“These findings suggest that aging is a risk factor for many people,” said a Yale University psychiatry lecturer who studies aging and was not involved in the study. MNT It seems the bone marrow transplant is affecting the entire body.
“Bone marrow transplants in younger people appear to improve immune system function both systemically and in the brain. The immune system appears to play an important role in clearing plaques in the brain that are a hallmark of Alzheimer's disease, and this study suggests that bone marrow transplants may help clear these plaques by rejuvenating the immune system,” he noted.
Trying to apply this procedure to humans is fraught with ethical problems, Hervanec warned, saying:[w]Given what we currently know, using bone marrow transplants in healthy people to study the prevention of age-related diseases is simply too risky.”
“The use of young allogeneic donors for proposed interventions against ageing, such as heterochronic parabiosis and bone marrow transplantation, is fraught with ethical concerns about fairness and exploitation and conjures up dystopian visions of a future in which billionaire 'vampires' obtain young blood and bone marrow to maintain their youth,” the researchers said.
“One way to get around this is to perform heterochronic autologous transplants – taking blood or bone marrow from a younger person and transplanting it back into oneself, which may have a similar effect. However, if research can identify specific aspects of these transplants that affect the ageing process (for example, blood proteins in serum seem to be important for heterochronic parabiosis), then benefits may be achievable even without a transplant. Either scenario reduces the risk of exploitation, but important ethical concerns about access to treatment remain.”
– Zachary Hervanek, MD
Still, despite the risks, Halvanek acknowledged that bone marrow transplants are a well-defined and ultimately safe treatment for people who need them to treat their illnesses.
