Tag: hyaluronic acid

Categories : Ageing GeneticsTags : Leave a comment

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

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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 : Diseases, Syndromes and ConditionsTags : Leave a comment

In Osteoarthritis, Molecular Changes Weaken Protective Films

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Photo by Towfiqu barbhuiya: https://www.pexels.com/photo/person-feeling-pain-in-the-knee-11349880/

Although osteoarthritis has been extensively studied through a medical perspective, the molecular changes associated with osteoarthritis remain unclear. New research published in Biointerphases suggests that there may be an optimum concentration and size of molecules in the synovial fluid needed to form the protective film in joints.

Osteoarthritis is the most common degenerative joint disease, affecting 22% of adults over 40 globally. The cartilage in the joints, in concert with the synovial fluid, provides a smooth surface to support weight-bearing movements. The fluid contains several molecules, including hyaluronan (HA) and phospholipids. Since the cartilage environment cannot be quickly healed or repaired, researchers have tried to diagnose the early stages of joint disease by monitoring the molecular weight and concentration of HA.

“Although we know that in healthy joints there is very low friction, it is unclear which other molecules are involved and how they change during osteoarthritis,” said Rosa Espinosa-Marzal (EIRH), professor of environmental engineering & science, and materials science & engineering. “During the early stages of osteoarthritis, cartilage starts degrading, and previous research has shown that the molecular composition of the synovial fluid changes. We wanted to see if the two changes are related to each other.”

In a healthy joint, the molecular weight of HA varies between 2–20 MDa with a concentration ranging from 1–4 mg/mL. Studies have shown that in diseased joints, HA is broken down resulting in a lower molecular weight and its concentration is also reduced by 10x. Based on these observations, made by other researchers, the study looked at how the concentration and molecular weight of HA influences the structure of healthy and diseased joints.

To do so, the researchers combined vesicles with high and low molecular weight HA. Using neutron scattering and light scattering, they discovered that the molecular weight of HA can vastly change the structure of the vesicles. Lower molecular weight HA, which mimics osteoarthritis-diseased joints, results in larger vesicle size. Changes in HA’s molecular weight also changed the thickness of the phospholipid layers in the joints.

The researchers also studied how these differences can influence the formation of a protective film; in joints this film is responsible for the very low friction we need for unhindered motion. Once again, they used a combination of techniques, quartz crystal microbalance and atomic force microscopy, to examine how these molecules assemble on gold surfaces.

“The formation of a film is possible only when there is an optimal concentration of HA and phospholipids. Even though the gold surfaces have very little in common with cartilage, our studies indicate that there could also be an optimum concentration under biological conditions,” Espinosa-Marzal said. “This is an important observation because we can use the concentration changes as a diagnostic tool.”

The researchers are now testing this theory using cartilage. They are also interested in studying the other molecular components that are found in joints to build a more comprehensive model of the changes that are associated with osteoarthritis.

Source: Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign

Categories : Pain ManagementTags : Leave a comment

Hyaluronic Acid of Little Value in Knee Osteoarthritis

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Knee pain
Source: CC0

Treating knee osteoarthritis with hyaluronic acid injections (known as viscosupplementation) makes almost no difference to pain or functioning and might raise risk of adverse events, suggests a review of 50 years of literature on the procedure.

Viscosupplementation has been used to treat knee osteoarthritis since the 1970s, but there are long-standing questions over its safety and efficacy.

Some 560 million people worldwide suffer from knee osteoarthritis, which involves inflammation and structural changes of the joints, resulting in joint pain and limitations to physical movement.

National and international guidelines vary in their recommendations, but most advise against the use of viscosupplementation. Researchers therefore set out to review 50 years’ worth of studies to evaluate the safety and efficacy of viscosupplementation. The studies compared viscosupplementation to placebo or no treatment.

Published in The BMJ, the main analysis of this review found that viscosupplementation was associated with a small reduction in pain compared with placebo, but the difference was tiny and was described as “clinically irrelevant.”

Their analysis showed that since 2009, there has been conclusive evidence that viscosupplementation and placebo treatment have led to the same clinical result in terms of pain reduction, meaning there is no point to having the injections.

They also found from 15 large trials on 6462 randomised participants that viscosupplementation was linked to a 49% higher risk of serious adverse events than placebo.

The authors say that based on their analysis of the studies between 2009 and 2021 alone, more than 12 000 patients were arguably unnecessarily subjected to these injections in viscosupplementation trials, which raises ethical concerns.

The study has some limitations in that it represents summary estimates and does not necessarily exclude the possibility that selected patient populations could benefit from viscosupplementation. Also, the researchers looked at adverse events that emerged rather than adverse events directly and clearly related to treatment.

However, strengths include the fact that this is the largest collection of randomised trials on viscosupplementation reported to date, which significantly decreases the risk of bias influencing the results.

As such, the authors conclude: “There is strong, conclusive evidence that among patients with knee osteoarthritis, viscosupplementation, compared with placebo, is associated with a clinically irrelevant reduction in pain intensity and with an increased risk of serious adverse events.

“The findings do not support broad use of viscosupplementation for the treatment of knee osteoarthritis.”

Source: The BMJ