Them bones them bones them dry bones – and how to help repair them

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Broken bones

People say that with age comes wisdom, kindness and confidence. What they usually don’t say is that it also comes with aches and pains and problems we didn’t have when we were younger. For example, as we get older our bones get thinner and more likely to break and less likely to heal properly.

That’s a depressing opening paragraph isn’t it. But don’t worry, things get better from here because new research from Germany has found clues as to what causes our bones to become more brittle, and what we can do to try and stop that.

Researchers at the Max Planck Institute for Biology of Ageing and CECAD Cluster of Excellence for Ageing Research at the University of Cologne have identified changes in stem cells from our bone marrow that seem to play a key role in bones getting weaker as we age.

To explain this we’re going to have to go into the science a little, so bear with me. One of the issues the researchers focused on is the role of epigenetics, this is genetic information that doesn’t change the genes themselves but does change their activity. Think of it like a light switch. The switch doesn’t change the bulb, but it does control when it’s on and when it’s off. So this team looked at the epigenome of MSCs, the stem cells found in the bone marrow. These cells play a key role in the creation of cartilage, bone and fat cells.

In a news release, Dr. Andromachi Pouikli, one of the lead researchers in the study, says these MSCs don’t function as well as we get older.

“We wanted to know why these stem cells produce less material for the development and maintenance of bones as we age, causing more and more fat to accumulate in the bone marrow. To do this, we compared the epigenome of stem cells from young and old mice. We could see that the epigenome changes significantly with age. Genes that are important for bone production are particularly affected.”

So, they took some stem cells from the bone marrow of mice and tested them with a solution of sodium acetate. Now sodium acetate has a lot of uses, including being used in heating pads, hand warmers and as a food seasoning, but in this case the solution was able to make it easier for enzymes to get access to genes and boost their activity.

“This treatment impressively caused the epigenome to rejuvenate, improving stem cell activity and leading to higher production of bone cells,” Pouikli said.

So far so good. But does this work the same way in people? Maybe so. The team analyzed MSCs from people who had undergone hip surgery and found that they showed the same kind of age-related changes as the cells from mice.

Clearly there’s a lot more work to do before we can even think about using this finding as a solution to aging bones. But it’s an encouraging start.

The study is published in the journal Nature Aging.

One thought on “Them bones them bones them dry bones – and how to help repair them

  1. Mechenchyma stem cells (MSCs) capable of self renewal and differentiation into variety of cell types. As they have low immunogenicity and can be safely transplanted autologously or allogenically. Thus, MSCs have many potential applications in cell-based therapy for various of disease states. However, MSCs of elderly people tend to gradually lose their regenerative potential with a concomitant increase in cellular dysfunction and replicative exhausted are considered hallmarks of aging. The inability of MSCs proliferate infinitely may undergo a limited number of population doubling before becoming senescent. Therefore, cells from age of donors are poor performance with reduced proliferative capacity and differentiation potential form a major factor to determine the lifespan and quality of MSCs. In addition, MSCs acquire senescent phenotype tend to loss their stem cell characteristics and stop from dividing, this pose negative impacts on immunomodulatory and differentiation capacity leading to reduce efficacy followong administration. As a result of DNA replication errors and exposure to endogenous or exogenous mutagens may cause DNA damage. The accumulation of DNA damage may induce irreversible cell cycle arrest and onset of senescent. The process of senescent cause mitochondria dysfunction and increase production of ROS which may induce DNA damage and accelerate telomere erosion. The absence of efficient repair mechanisms in DNA mitochondria (mtDNA) may increase mutation rate of mtDNA compared to nuclear DNA. Mitochondria has important roles in cellular function, it involves energy production, intracellular homeostasis, calcium balance and metabolisms. The impair on DNA repairing capacity of mitochondria cause most of the neurodegenerative diseases in elderly population.

    There are several strategies to rejuvenate senescent MSCs: 1)iPSC derived MSCs can be passaged more than 40 times without exhibiting features of senescent. They retain donor-specific DNA replication profile while tissue -specific senescent associated with age–related patterns are erased during reprogramming. 2)Modulated through several key signaling molecules. Mitochondria SIRTs act as stress sensors and regulate protein networks to coordinate the stress responses. Overexpression of SIRTs as a potential strategy to prevent MSCs from aging 3)Genetics engineering to slow MSCs aging. Ectopic expression of telomerase reverse transcriptase in MSCs extend their replicative lifespan, preserved a normal karyotype, promote telomere elongation and abolished senensent without loss of differentiation potential. 4)Pharmacologic approaches and cytokine supplementation for delaying senescent. The restoring cytosolic acetyl-CoA levels by acetate supplementation to rescue the osteogenesis defects of elderly.

    All cells require growth factors for survival, growth, differentiation and behavior. The removal of growth factor from a dependent cell does not always result in simple growth arrest but can in some cases lead to the rapid initiation of cellular program of self-destruction or apoptosis. Given the basic conditions for survival, subsequent growth factor-mediatd cell responses involve changes in proliferative activity, differentiation state, or behavior practice. Lack of growth factors may halt the development state of cell, alteration the availability of stimuli, the level of functional receptors, the composition of signaling transduction network, or the response capability of ultimate targets of signal transduction. Therefore, the precipitation of cellular program in cell has great impact in the generation of transformed phenotype such as senescent of cells and hence of cancer. As men and women attain the stage of menopause, lack of growth factors and growth hormones are cause of concern to alter the integrity of cells and generate many kinds of severe illnesses and diseases. The healthy lifestyle, diets and nutrition supplemention may provide additional support to improve the health of cells for functioning.

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