Just like your future body will thank you for the apple, your future ears (specifically your cochlear hair cells) will thank you for protecting them. The most common cause of hearing loss is progressive because these hair cells — the primary cells to detect sound waves — cannot regenerate if damaged or lost. People who have repeated exposure to loud noises, like military personnel, construction workers, and musicians, are most at risk for this type of hearing loss. But, it can happen to anyone over time (even concert goers).

On the other hand, birds and fish can regenerate these hair cells, and now researchers at the Del Monte Institute for Neuroscience are getting closer to identifying the mechanisms that may promote this type of regeneration in mammals, as explained in research recently published in Frontiers in Cellular Neuroscience.

“We know from our previous work that expression of an active growth gene, called ERBB2, was able to activate the growth of new hair cells (in mammals), but we didn’t fully understand why,” said Patricia White, PhD, professor of Neuroscience and Otolaryngology at the University of Rochester Medical Center. The 2018 study led by Jingyuan Zhang, PhD, a postdoctoral fellow in the White lab at the time, found that activating the growth gene ERBB2 pathway triggered a cascading series of cellular events by which cochlear support cells began to multiply and activate other neighboring stem cells to become new sensory hair cells.

“This new study tells us how that activation is happening — a significant advance toward the ultimate goal of generating new cochlear hair cells in mammals,” said White.

Using single-cell RNA sequencing in mice, researchers compared cells with an overactive growth gene (ERBB2 signaling) with similar cells that lacked such signaling. They found the growth gene — ERBB2 — promoted stem cell-like development by initiating the expression of multiple proteins — including SPP1, a protein that signals through the CD44 receptor. The CD44 receptor is known to be present in cochlear-supporting cells. This increase in cellular response promoted mitosis in the supporting cells, a key event for regeneration.

“When we checked this process in adult mice, we were able to show that ERBB2 expression drove the protein expression of SPP1 that is necessary to activate CD44 and grow new hair cells,” said Dorota Piekna-Przybylska, PhD, a staff scientist in the White Lab and first author of the study. “This discovery has made it clear that regeneration is not only restricted to the early stages of development. We believe we can use these findings to drive regeneration in adults.”

“We plan to further investigation of this phenomenon from a mechanistic perspective to determine whether it can improve auditory function after damage in mammals. That is the ultimate goal,” said White.

Additional authors include Daxiang Na, Cameron Baker, and John Ashton, PhD, at the University of Rochester and Medical Center. The research was supported by the U.S. Army Medical Research Mechanism, the National Institute on Deafness and Other Communication Disorders, UR Ventures, and the Schmitt Program on Integrative Neuroscience.

Physical activity at different times of the day can affect the body in different ways since the biological processes depend on the circadian rhythms of the cells. To ascertain how the time of day at which exercise is done affects the burning of fat, researchers at Karolinska Institutet and the University of Copenhagen studied the adipose tissue of mice after a session of high-intensity exercise performed at two points of the daily cycle, an early active phase and early rest phase (corresponding to a late morning and late evening session, respectively, in humans). The researchers studied various markers for fat metabolism and analysed which genes were active in adipose tissue after exercise.

Independent of food intake

The researchers found that physical activity at an early active phase increased the expression of genes involved in the breakdown of adipose tissue, thermogenesis (heat production) and mitochondria in the adipose tissue, indicating a higher metabolic rate. These effects were observed only in mice that exercised in the early active phase and were independent of food intake.

“Our results suggest that late morning exercise could be more effective than late evening exercise in terms of boosting the metabolism and the burning of fat, and if this is the case, they could prove of value to people who are overweight,” says Professor Juleen R. Zierath from the Department of Molecular Medicine and Surgery and the Department of Physiology and Pharmacology, Karolinska Institutet.

Improve the health benefits of exercise

Mice and humans share many basic physiological functions, and mice are a well-established model for human physiology and metabolism. However, there are also important differences, such as the fact that mice are nocturnal.

“The right timing seems to be important to the body’s energy balance and to improving the health benefits of exercise, but more studies are needed to draw any reliable conclusions about the relevance of our findings to humans,” says Professor Zierath.

The study was conducted in close collaboration with the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR) at the University of Copenhagen and was financed by the Novo Nordisk Foundation, Novo Nordisk, the Swedish Diabetes Foundation, the Swedish Research Council and Karolinska Institutet.