HAS2

In a groundbreaking endeavor, researchers have successfully transferred a longevity gene from naked mole rats to mice, resulting in improved health and an extension of the mouse's lifespan. The research opens exciting possibilities for unlocking the secrets of aging and extending human lifespan. In a groundbreaking endeavor, researchers at the University of Rochester have successfully transferred a longevity gene from naked mole rats to mice, resulting in improved health and an extension of the mouse's lifespan. Naked mole rats, known for their long lifespans and exceptional resistance to age-related diseases, have long captured the attention of the scientific community. By introducing a specific gene responsible for enhanced cellular repair and protection into mice, the Rochester researchers have opened exciting possibilities for unlocking the secrets of aging and extending human lifespan. "Our study provides a proof of principle that unique longevity mechanisms that evolved in long-lived mammalian species can be exported to improve the lifespans of other mammals," says Vera Gorbunova, the Doris Johns Cherry Professor of biology and medicine at Rochester. Gorbunova, along with Andrei Seluanov, a professor of biology, and their colleagues, report in a study published in Nature that they successfully transferred a gene responsible for making high molecular weight hyaluronic acid (HMW-HA) from a naked mole rat to mice. This led to improved health and an approximate 4.4 percent increase in median lifespan for the mice. A unique mechanism for cancer resistance Naked mole rats are mouse-sized rodents that have exceptional longevity for rodents of their size; they can live up to 41 years, nearly ten times as long as similar-size rodents. Unlike many other species, naked mole rats do not often contract diseases -- including neurodegeneration, cardiovascular disease, arthritis, and cancer -- as they age. Gorbunova and Seluanov have devoted decades of research to understanding the unique mechanisms that naked mole rats use to protect themselves against aging and diseases. The researchers previously discovered that HMW-HA is one mechanism responsible for naked mole rats' unusual resistance to cancer. Compared to mice and humans, naked mole rats have about ten times more HMW-HA in their bodies. When the researchers removed HMW-HA from naked mole rat cells, the cells were more likely to form tumors. Gorbunova, Seluanov, and their colleagues wanted to see if the positive effects of HMW-HA could also be reproduced in other animals. Transferring a gene that produces HMW-HA The team genetically modified a mouse model to produce the naked mole rat version of the hyaluronan synthase 2 gene, which is the gene responsible for making a protein that produces HMW-HA. While all mammals have the hyaluronan synthase 2 gene, the naked mole rat version seems to be enhanced to drive stronger gene expression. The researchers found that the mice that had the naked mole rat version of the gene had better protection against both spontaneous tumors and chemically induced skin cancer. The mice also had improved overall health and lived longer compared to regular mice. As the mice with the naked mole rat version of the gene aged, they had less inflammation in different parts of their bodies -- inflammation being a hallmark of aging -- and maintained a healthier gut. While more research is needed on exactly why HMW-HA has such beneficial effects, the researchers believe it is due to HMW-HA's ability to directly regulate the immune system. A fountain of youth for humans? The findings open new possibilities for exploring how HMW-HA could also be used to improve lifespan and reduce inflammation-related diseases in humans. "It took us 10 years from the discovery of HMW-HA in the naked mole rat to showing that HMW-HA improves health in mice," Gorbunova says. "Our next goal is to transfer this benefit to humans." They believe they can accomplish this through two routes: either by slowing down degradation of HMW-HA or by enhancing HMW-HA synthesis. "We already have identified molecules that slow down hyaluronan degradation and are testing them in pre-clinical trials," Seluanov says. "We hope that our findings will provide the first, but not the last, example of how longevity adaptations from a long-lived species can be adapted to benefit human longevity and health."

A new study reveals a unique form of cell communication that controls muscle repair. A new study published in the journal Science reveals a unique form of cell communication that controls muscle repair. In damaged muscle, stem cells must work together with immune cells to complete the repair process, yet how these cells coordinate to ensure the efficient removal of dead tissue before making new muscle fibers has remained unknown. The scientists have now shown that a natural substance called hyaluronic acid, which is used in cosmetics and injections for osteoarthritis, is the key molecule that manages this fundamental interaction. "When muscles get damaged, it is important for immune cells to quickly enter the tissue and remove the damage before stem cells begin repair," said Dr. Jeffrey Dilworth, senior scientist at The Ottawa Hospital and professor at the University of Ottawa and senior author on the study. "Our study shows that muscle stem cells are primed to start repair right away, but the immune cells maintain the stem cells in a resting state while they finish the cleanup job. After about 40 hours, once the cleanup job is finished, an internal alarm goes off in the muscle stem cells that allows them to wake up and start repair." Dr. Dilworth and his team identified hyaluronic acid as the key ingredient in this internal alarm clock that tells muscle stem cells when to wake up. When muscle damage occurs, stem cells start producing and coating themselves with hyaluronic acid. Once the coating gets thick enough, it blocks the sleep signal from the immune cells and causes the muscle stem cells to wake up. Using mouse and human tissues, Dr. Dilworth and his team also discovered how muscle stem cells control the production of hyaluronic acid using epigenetic marks on the Has2 gene. "Interestingly, aging is associated with chronic inflammation, muscle weakness and a reduced ability of muscle stem cells to wake up and repair damage," said lead author Dr. Kiran Nakka, a research associate with Dr. Dilworth who conducted this research as part of his postdoctoral studies. "If we could find a way to enhance hyaluronic acid production in the muscle stem cells of older people it might help with muscle repair." The authors note that the regenerative effect of hyaluronic acid seems to depend on it being produced by the muscle stem cells. The team is currently examining if drugs that modify the epigenetics of muscle stem cells could be used to increase their production of hyaluronic acid.