Tag: mouse study

Categories : Ageing GeneticsTags :

Mice Live Longer when Given a Longevity Gene from Naked Mole Rats

On By ModernMedia
CRISPR-Cas9 is a customisable tool that lets scientists cut and insert small pieces of DNA at precise areas along a DNA strand. This lets scientists study our genes in a specific, targeted way. Credit: Ernesto del Aguila III, National Human Genome Research Institute, NIH

In a ground-breaking advance in aging research, scientists 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 are known for their long lifespans and exceptional resistance to age-related diseases. By introducing a specific gene responsible for enhanced cellular repair and protection into mice, the 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, professor at Rochester University. 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 age-related diseases such neurodegeneration, cardiovascular disease, arthritis, and cancer. 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 tumours.

Gorbunova, Seluanov, and their colleagues wanted to see if the positive effects of HMW-HA could also be reproduced in other animals.

Transferring an HMW-HA-producing gene

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?

“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.”

Source: University of Rochester

Categories : AgeingTags :

CSF From Young Mice Improves Memory of Older Mice

On By ModernMedia
Mouse
Photo by Kanasi on Unsplash

In a finding reminiscent of how vampires and zombies in fiction get sustenance from their victims, a team of researchers reported in the journal Nature that injecting cerebrospinal fluid (CSF) from young mice into old mice improves the memory and cognitive abilities of the older mice

Such an approach is nothing new, although the chief obstacle was safely harvesting such a tiny amount of CSF from the small animals. About two decades ago, studies had reported that transferring blood from younger mice to older ones notably improved the health of the older mice, giving them a ‘rejuvenating’ effect. It did not take long for people to take note of this discovery, with a startup company offering transfers of young people’s plasma for exorbitant amounts to wealthy older clients in the unproven hopes of reversing ageing. Fears of a dystopian future were averted when the US Food and Drug Administration released a statement stating such transfers had no clinical benefit, and the company folded. However, research continued.

Since ageing is too complex to measure in a clinical trial anyway, scientists have been focusing on tackling specific aspects of it, such as in neurodegenerative diseases like Alzheimer’s and research has continued in this direction. A few years ago, human umbilical cord plasma was shown to revitalise hippocampal function in aged mice, and previous work led by Tony Wryss-Coray, PhD had found that young mouse blood improved age-related impairments in cognition. Studies of fear conditioning had shown that proliferation of oligodendrocyte precursor cells (OPCs) was necessary for fear formation, which raised the question of whether CSF might affect this.

Infusing CSF taken from 10 week old mice over seven days, researchers trained 18 month old mice to associate a flashing light with an electric shock to the foot. The CSF infusion was shown to improve recall of the fear stimulus in the older mice and induce greater OPC proliferation.

“The broad message here is that the aging process is malleable, which of course is not new because of this paper,” senior author Dr Wyss-Coray said in an interview with MedPage Today. “But it adds to the idea that aging is a potential therapeutic target, a process we can start to understand better and start to manipulate.”

“The other message – one that’s more brain-specific – is that if you improve the environment in which neurons live, you can actually have a substantial improvement in function,” he added. “That may be as important, or even more important sometimes, than targeting neuronal processes themselves.”

The researchers isolated fibroblast growth factor 17 (Fgf17) infusion as being necessary for OPC proliferation, and blocking it in young mice impaired cognition.

“This suggests that Fgf17 is not only able to recapitulate some of the useful effects of CSF from young mice, but it also seems to be necessary to make a young brain function at its full capacity,” Dr Wyss-Coray said.

Categories : COVIDTags :

Why COVID Cases Vary in Severity

On By ModernMedia
Source: Fusion Medical Animation on Unsplash

Researchers working with ‘humanised mice’ have found why some mild cases of COVID tip over into more severe and life-threatening disease.

An estimated 80 to 90% of people infected with COVID experience only mild cases while 10 to 20% face more severe or life-threatening symptoms.

Yale University researchers working with mice they have engineered to possess human-like immune systems may have found why this is so. Their findings,  published in Nature Biotechnology revealed that the causes of severe COVID may lie in our own antiviral inflammatory response to the virus.

The study also showed that two well-known therapies, monoclonal antibodies and the steroid dexamethasone, can help treat COVID infections. But in the case of the antibodies, treatment is only effective if administered early in the course of disease. In the case of steroids, it’s only effective if administered during later stages of the disease.

Standard laboratory animals and humans have different immune responses, which has made it difficult for scientists to pinpoint the tipping point between mild and severe cases of COVID, so mice engineered to have a human-like immune system, were able to offer an answer.

“If you infect a standard laboratory mouse with SARS-CoV-2 they will get infected, but not get seriously ill,” said Flavell, Sterling Professor of Immunobiology at Yale and senior author of the paper. “But our humanised mice get sick and just don’t get better. Their whole immune system is on fire.”

The research team introduced SARS-CoV-2 virus taken from seriously ill human patients into the nasal passages of their humanised mice and then followed the course of the disease.

They found that the infected mice exhibited the same symptoms as severely ill human patients, such as lung damage, weight loss, and a heightened, persistent inflammatory immune response that damages tissues. They then treated the mice with monoclonal antibodies which specifically target the virus, and were  found to be effective if given before or very early after infection but did little to stifle symptoms if administered in later stages of infections.

Conversely, during the early stages of infection the immune suppressant dexamethasone was fatal to mice when it suppressed the initial immune response that was crucial to combat the virus. However, during later stages of disease, it helped clear infection  by suppressing the inflammatory response that had begun damaging organs.

“Early in the course of disease, a strong immune response is crucial for survival,” said first author Esen Sefik. “Later in the disease, it can be fatal.”

The humanised mice models might also reveal strong clues to the causes and potential treatments of so-called long and severe COVID, the scientists said.

Source: Yale University