Cell Metabolism

Could stem cells help reverse hair loss?

/ Kevin McCormack / Leave a comment

I thought that headline would grab your attention. The idea behind it grabbed my attention when I read about a new study in the journal Cell Metabolism that explored that idea and came away with a rather encouraging verdict of “perhaps”.

The research team from the University of Helsinki say that on average people lose 1.5 grams of hair every day, which over the course of a year adds up to more than 12 pounds (I think, sadly, this is the one area where I’m above average.) Normally all that falling hair is replaced by stem cells, which generate new hair follicles. However, as we get older, those stem cells don’t work as efficiently which explains why so many men go bald.

In a news release, lead author Sara Wickstrom says this was the starting point for their study.

“Although the critical role of stem cells in ageing is established, little is known about the mechanisms that regulate the long-term maintenance of these important cells. The hair follicle with its well understood functions and clearly identifiable stem cells was a perfect model system to study this important question.”

Previous studies have shown that after stem cells create new hair follicles they essentially take a nap (resume a quiescent state in more scientific parlance) until they are needed again. This latest study found that in order to do that the stem cells have to change their metabolism, reducing their energy use in response to the lower oxygen tissue around them. The team identified a protein called Rictor that appears to be the key in this process. Cells with low levels of Rictor were less able to wake up when needed and generate more hair follicles. Fewer replacements, bigger gaps in the scalp.

The team then created a mouse model to test their theory. Sure enough, mice with low or no Rictor levels were less able to regenerate hair follicles. Not surprisingly this was most apparent in older mice, who showed lower Rictor levels, decreased stem cell activity and greater hair loss.

Sara Wickstrom says this could point to new approaches to reversing the process.

“We are particularly excited about the observation that the application of a glutaminase inhibitor was able to restore stem cell function in the Rictor-deficient mice, proving the principle that modifying metabolic pathways could be a powerful way to boost the regenerative capacity of our tissues,”

It’s early days in the research so don’t expect them to be able to put the Hair Club for Men out of business any time soon. But a follicle-challenged chap can dream can’t he.

CIRM-funded Stanford study finds potential diagnostic tool, treatment for Parkinson’s

/ Yimy Villa / Leave a comment
Dr. Xinnan Wang, a neurosurgeon and author of a study that has identified a molecular pathway apparently responsible for the death of dopaminergic neurons that causes the symptoms of Parkinson’s.

Of the various neurodegenerative diseases, Parkinson’s is the second most common and affects 35 million people world wide. It is caused by the gradual breakdown of dopaminergic neurons in the brain, which are a type of cell that produce a chemical in your brain known as dopamine.  This decrease in dopamine can cause complications such as uncontrollable shaking of the hands, slowed movement, rigid muscles, loss of automatic movements, speech changes, bladder problems, constipation, and sleep disorders.

Although 5-10% of cases are the result of genetically inherited mutations, the vast majority of cases are sporadic, often involving complex interactions of multiple unknown genes and environmental factors. Unfortunately, it is this unknown element that make the disease very difficult to detect early on in the majority of patients.

However, in a CIRM funded study, Dr. Xinnan Wang and her team at Stanford University were able to pinpoint a molecular defect that seems almost universal in patients with Parkinson’s and those at high risk of acquiring it. This could prove to be a way to detect Parkinson’s in its early stages and before symptoms start to manifest. Furthermore, it could also be used to evaluate a potential treatment’s effectiveness at preventing or stalling the progression of Parkinson’s.

In a Stanford press release, Dr. Wang explains the implications of these findings:

“We’ve identified a molecular marker that could allow doctors to diagnose Parkinson’s accurately, early and in a clinically practical way. This marker could be used to assess drug candidates’ capacity to counter the defect and stall the disease’s progression.” 

What is more astounding is that Dr. Wang and her team were also able to identify a compound that is shown to reverse the defect in cells taken from Parkinson’s patients. In an animal model, the compound was able to prevent the death of neurons, which is the underlying problems in the disease.

In their study, Dr. Wang and her team focused on the mitochondria, which churns out energy and is the powerhouse of the cell. Dopaminergic neurons in the brain are some of the body’s hardest working cells, and it is theorized that they start to die off when the mitochondria burns out after constant, high energy production.

Mitochondria spend much of their time attached to a grid of protein “roads” that crisscross cells. Our cells have a technique for clearing “burnt out” mitochondria, but the process involves removing an adaptor molecule called Miro that attaches mitochondria, damaged or healthy, to the grid. 

Dr. Wang’s team previously identified a mitochondrial-clearance defect in Parkinson’s patients’ cells that involved the inability to remove Miro from damaged mitochondria.

In the current study, they obtained skin samples from 83 Parkinson’s patients, Five patients with asymptomatic close relatives considered to be at heightened risk, 22 patients diagnosed with other movement disorders, and 52 healthy control subjects. They extracted fibroblasts, which are cells common in skin tissue, from the samples and subjected them to a stressful process that messes up mitochondria. 

The researchers found the Miro-removal defect in 78 of the 83 Parkinson’s fibroblasts (94%) and in all five of the “high-risk” samples, but not in fibroblasts from the control group or patients with other movement-disorders.

Next, the team was able to screen over 6.8 million molecules and found 11 that would bind to Miro, initiating separation from the mitochondria, are non-toxic, orally available, and able to cross the blood-brain barrier. These 11 compounds were tested in fruit flies and and ultimately one of them, which seems to target Miro exclusively, was tested on fibroblasts from a patient with sporadic Parkinson’s disease. The compound was found to substantially improved Miro clearance in these cells after their exposure to mitochondria-damaging stress.

Dr. Wang is optimistic that clinical trials of the compound or something similar are no more than a few years off.

In the same Stanford press release, Dr. Wang stated that,

“Our hope is that if this compound or a similar one proves nontoxic and efficacious and we can give it, like a statin drug, to people who’ve tested positive for the Miro-removal defect but don’t yet have Parkinson’s symptoms, they’ll never get it.”

The full results of this study were published in the journal Cell Metabolism.

Salk scientists discover new findings related to the age of organs

/ Yimy Villa / 1 Comment
Dr. Rafael Arrojo e Drigo (left) and Dr. Martin Hetzer (right) at the Salk Institute in San Diego

It has been a long held belief in the scientific community that nerve cells, or possibly the heart, are the oldest cells in the body. This is due to the fact that the brain and heart are the first organs that begin to develop in the womb. Nerve cells have an average lifespan of approximately 80 years without the need of generating new cells. It has been difficult to determine the approximate age of other organs such as the liver and pancreas in the body until now.

Dr. Rafael Arrojo e Drigo and Dr. Martin Hetzer, scientists at the Salk Institute, have discovered a population of cells that reside in the mouse brain, liver, and pancreas that have extremely long lifespans. In some cases, some of these cells were the same age as the animal they were found in. The scientists used a complex labeling and imaging procedure to determine cell age in a mouse model.

Furthermore, the scientists also found that the brain, liver, and pancreas in the mice contain a mixture of “old” and “young” cells, like a mosaic painting composed of small, different colored pieces. They called this phenomenon age mosaicism, referring to the population of identical cells that could only be distinguished by lifespan.

Their method could be applied to other types of tissue in the body, which could provide valuable information, such as the lifelong function of non-dividing cells and how cells lose control over the quality and integrity of important cell structures during aging. The answers to these questions play a key role in understanding ways to prevent the age-related degeneration of organs, such as the brain in Alzheimer’s Disease or the pancreas in Type II Diabetes.

In a press release, Dr. Hetzer is quoted as saying that,

“Determining the age of cells and subcellular structures in adult organisms will provide new insights into cell maintenance and repair mechanisms and the impact of cumulative changes during adulthood on health and development of disease. The ultimate goal is to utilize these mechanisms to prevent or delay age-related decline of organs with limited cell renewal such as the brain, pancreas and heart.”

The full results of the study were published in Cell Metabolism.

You can also see a youtube video below of Dr. Rafael Arrojo e Drigo and Dr. Martin Hetzer discussing their findings.