Epigenetics

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

/ Kevin McCormack / 1 Comment

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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.

How regrowing tiny hairs could restore hearing loss

/ Kevin McCormack / 3 Comments
Man getting fitted with hearing aids

Hearing loss is something that affect tens of millions of Americans. Usually people notice those changes as they get older but the damage can be done years before that through the use of some prescription drugs or exposure to loud noise (I knew I shouldn’t have sat in the 6th row of that Led Zeppelin concert!)

Now researchers at the University of Southern California (USC) have identified the mechanism that appears to stop cells that are crucial to hearing from regenerating.

In a news release Dr. Neil Segil says this could, in theory, help reverse some hearing loss.  “Permanent hearing loss affects more than 60 percent of the population that reaches retirement age. Our study suggests new gene engineering approaches that could be used to channel some of the same regenerative capability present in embryonic inner ear cells.”

The inner ear has two types of cells that are crucial for hearing; “hair cells” are sensory receptors and these help the brain detect sounds, and support cells that play, as the name implies, an important structural and supporting role for the hair cells.

In people, once the hair cells are damaged that’s it, you can’t repair or replace them and the resulting hearing loss is permanent. But mice, in the first few days of life, have ability to turn some of their support cells into hair cells, thus repairing any damage. So Segil and the team set out to identify how mice were able to do that and see if those lessons could be applied to people.

They identified specific proteins that played a key role in turning genes on and off, regulating if and when the support cells could turn into hair cells. They found that one molecule, H3K4mel, was particularly important in activating the correct genetic changes need to turn the support cells into hair cells. But in mice, levels of H3K4mel disappeared quickly after birth, so the team found a drug that helped preserve the molecule, meaning the support cells retained the ability to turn into hair cells.

Now, obviously because this was just done in mice there’s a lot more work that needs to be done to see if it can also work in people, but Segil says it’s certainly an encouraging and intriguing start.

“Our study raises the possibility of using therapeutic drugs, gene editing, or other strategies to make epigenetic modifications that tap into the latent regenerative capacity of inner ear cells as a way to restore hearing. Similar epigenetic modifications may also prove useful in other non-regenerating tissues, such as the retina, kidney, lung, and heart.”

The study is published in the journal Developmental Cell

CIRM has funded several projects targeting hearing loss. You can find them here.