Researchers Discover Anti-inflammatory Molecules That Decline in the Aging Brain - World Health Informatics Blog. (community health)

Researchers Discover Anti-inflammatory Molecules That Decline in the Aging Brain - World Health Informatics Blog. (community health)

Summary: SGDGs, a class of lipids that decline in the brain during aging, appear to have anti-inflammatory effects that could have implications for neurodegenerative disorders.

Source: Salk Institute

Aging involves complicated plot twists and a large cast of characters: inflammation, stress, metabolism changes, and many others.

Now, a team of Salk Institute and UC San Diego scientists reveal another factor implicated in the aging process—a class of lipids called SGDGs (3-sulfogalactosyl diacylglycerols) that decline in the brain with age and may have anti-inflammatory effects.

The research, published in Nature Chemical Biology on October 20, 2022, helps unravel the molecular basis of brain aging, reveals new mechanisms underlying age-related neurological diseases, and offers future opportunities for therapeutic intervention.

“These SGDGs clearly play an important role in aging, and this finding opens up the possibility that there are other critical aging pathways we’ve been missing,” says co-corresponding author Alan Saghatelian, professor in Salk’s Clayton Foundation Laboratories for Peptide Biology and holder of the Dr. Frederik Paulsen Chair. “This is a pretty clear case of something that should be dug into more in the future.”

SGDGs are a class of lipids, also called fats. Lipids contribute to the structure, development, and function of healthy brains, while badly regulated lipids are linked to aging and diseased brains.

However, lipids, unlike genes and proteins, are not well understood and have often been overlooked in aging research. Saghatelian specializes in discovering new lipids and determining their structures.

His lab, in collaboration with Professor Dionicio Siegel at UC San Diego, made three discoveries involving SGDGs: In the brain, lipid levels are very different in older mice than in younger mice; all SGDG family members and related lipids change significantly with age; and SGDGs may be regulated by processes that are known to regulate aging.

To reach these findings, the team took an unusual, exploratory approach that combined the large-scale study of lipids (lipidomics) with structural chemistry and advanced data analytics.

They first obtained lipid profiles of mouse brains at five ages, ranging from one to 18 months, using liquid chromatography-mass spectrometry. Technological advances in this instrumentation vastly expanded the number of data points available to the scientists, and advanced data analysis allowed them to determine age-related patterns in the enormous lipid profiles.

The team then constructed SGDG molecules and tested them for biological activity.

“SGDGs were first identified in the 1970s, but there were few follow-up studies. These lipids were essentially forgotten and missing from the lipid databases. Nobody knew SGDGs would be changing or regulated in aging, let alone that they have bioactivity and, possibly, be therapeutically targetable,” says first author Dan Tan, a postdoctoral fellow in Saghatelian’s lab at Salk.

The analysis showed that SGDGs possess anti-inflammatory properties, which could have implications for neurodegenerative disorders and other neurological conditions that involve increased inflammation in the brain.

The team also discovered that SGDGs exist in human and primate brains, suggesting that SGDGs may play an important role in animals other than mice. Further research will be required to show if SGDGs contribute to human neuroinflammation.

In the future, the team will examine how SGDGs are regulated with aging and what proteins are responsible for making them and breaking them down, which may open the door to discovering novel genetic activity associated with aging.

“With the understanding of the structure of SGDGs and our ability to create them in the laboratory, the study of these important lipids is now wide open and ripe for discovery,” says Siegel, co-corresponding author of the study.

Additional authors included Meric Erikci Ertunc, Justin Wang, Tina Chang, Antonio F. M. Pinto, Andrea Rocha, Cynthia J. Donaldson, Joan M. Vaughan, Peter C. Gray, Pamela Maher, and Nicola J. Allen of Salk; Srihari Konduri of UC San Diego; Pan Zhang of UC Los Angeles; Raissa G. Ludwig and Marcelo A. Mori of the University of Campinas, Brazil; Elizabeth Willey and Andrew Dillin of UC Berkeley; Manasi Iyer and Bradley Zuchero of Stanford University; and Steven G. Kohama of Oregon Health and Science University.

Funding: This work was funded by Ferring Pharmaceuticals and Frederik Paulsen, the National Institutes of Health (P30 CA014195, R01DK106210, R01NS119823, R01AG069206 and RF1AG061296), the Oregon National Primate Research Center (P51 OD 010092), the Wu Tsai Human Performance Alliance and the Joe and Clara Tsai Foundation, the Anderson Foundation, the Bruce Ford and Anne Smith Bundy Foundation, the Pioneer Fellowship, the Howard Hughes Medical Institute, the CZI Neurodegeneration Network, and The Sãn Paulo Research Foundation (2017/01184-9).

About this aging and neuroscience research news

Author: Salk Communications

Source: Salk Institute

Contact: Salk Communications – Salk Institute

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World Health Informatics Blog. (community health)

Note :

1) This blog is originally published on 

https://neurosciencenews.com/sgdgs-aging-inflammation-21758/

2) This Blog is for Education purpose only and not a treatment for any diseases  

Image: The image is credited to Salk Institute

Newly discovered species of bacteria in the microbiome may be a culprit behind rheumatoid arthritis World Health Informatics Blog. (community health)

 Newly discovered species of bacteria in the microbiome may be a culprit behind rheumatoid arthritis

World Health Informatics Blog. (community health)

Rheumatoid arthritis affects 1 in 100 people worldwide. It causes inflamed, painful and swollen joints, often in the hands and wrists, and can lead to loss of joint function as well as chronic pain and joint deformities and damage. What causes this condition has been unknown.

In our recently published study, my colleagues and I found an important clue to a potential culprit behind this disease: the bacteria in your gut.

What causes rheumatoid arthritis?

Rheumatoid arthritis is an autoimmune condition, meaning it develops when the body’s immune system starts to attack itself. Proteins called antibodies, which usually help fight off viruses and bacteria, begin to attack the joints instead.

The origins of the antibodies that cause rheumatoid arthritis have been an area of study for many years. Some research has shown that these antibodies can start forming at sites like the mouth, lung and intestines over 10 years before symptoms arise. But until now, it was unclear why researchers were finding these antibodies in these particular areas.

We wanted to investigate what could trigger the formation of these antibodies. Specifically, we wondered if bacteria in the microbiome, a community of microorganisms that live in the intestines, might be the ones activating the immune response that leads to rheumatoid arthritis. Since microbes commonly live at the same sites as the antibodies driving rheumatoid arthritis, we hypothesized that these bacteria could be triggering the production of these antibodies. We reasoned that though these antibodies were meant to attack the bacteria, rheumatoid arthritis develops when they spread beyond the intestines to attack the joints.

First, we sought to identify the intestinal bacteria targeted by these antibodies. To do this, we exposed the bacteria in the feces of a subset of people at risk for developing rheumatoid arthritis to these antibodies, allowing us to isolate just the bacterial species that reacted and bound to the antibodies.

We found that one previously unknown species of bacteria was present in the intestines of around 20% of people who were either diagnosed with rheumatoid arthritis or produce the antibodies that cause the disease. As a member of the Cherokee Nation of Oklahoma, I suggested we name this species Subdoligranulum didolesgii (“didolesgii” means arthritis or rheumatism in Cherokee) as a nod to the contributions that other Indigenous scholars have made to science as well as the fact that rheumatoid arthritis affects Indigenous people at a higher rate than other populations.

Subdoligranulum didolesgii has not been detected in the feces of healthy people before, and it is currently unknown how prevalent this bacteria is in the general population.

We also found that these bacteria can activate specialized immune cells called T cells in people with rheumatoid arthritis. T cells drive inflammatory responses in the body, and have been linked to the development of different autoimmune diseases.

These findings suggest that these gut bacteria may be activating the immune systems of people with rheumatoid arthritis. But instead of attacking the bacteria, their immune system attacks the joints.

Why this bacteria?

It is still unknown why people with rheumatoid arthritis develop an immune response to Subdoligranulum didolesgii. But we think it may be the culprit when it comes to rheumatoid arthritis because this bacteria is found only in the intestines of people with rheumatoid arthritis, and not in the intestines of healthy people.

While many immune responses happen in the intestines, they are usually self-contained and do not spread to other areas of the body. However, we believe that a particularly strong intestinal immune response against Subdoligranulum didolesgii could allow antibodies to bypass the intestinal “firewall” and spread to the joints.

To confirm our hypothesis, we gave mice an oral dose of Subdoligranulum didolesgii and monitored their reaction. Within 14 days, the mice began to develop joint swelling and antibodies that attacked their joints.

The future of rheumatoid arthritis treatment

My colleagues and I hope this research can shed light on the origins of rheumatoid arthritis. Our next goal is to discover how common these bacteria are in the general population and test whether the presence of these bacteria in the gut may lead to the development of rheumatoid arthritis in people.

It’s important to note that antibiotics are unlikely to be helpful treatment for the microbiomes of patients with rheumatoid arthritis. Although Subdoligranulum didolesgii may be triggering an autoimmune response for some people with rheumatoid arthritis, antibiotics eliminate both helpful and harmful bacteria in the gut. Additionally, removing the bacteria won’t necessarily stop the immune system from attacking the joints once it has started.

Nevertheless, we believe that these bacteria can be used as tools to develop treatments for rheumatoid arthritis and hopefully ways to prevent disease from happening in the first place.

Thank you

World Health Informatics Blog. (community health)

Note :

1) This blog is originally published on 

https://theconversation.com/newly-discovered-species-of-bacteria-in-the-microbiome-may-be-a-culprit-behind-rheumatoid-arthritis-193267

2) This Blog is for Education purpose only and not a treatment for any diseases  

Sleeping 5 hours or less could prompt risk of chronic diseases - World Health Informatics Blog. (community health)

 

Sleeping 5 hours or less could prompt risk of chronic diseases later in life, study says

 World Health Informatics Blog. (community health)

People over 50 years old who sleep five hours or less a night might be at higher risk of developing multiple chronic diseases, according to a new study released Oct. 18.  

The peer-reviewed study, published in the journal PLOS Medicine, examined 8,000 civil servants in the United Kingdom who had no chronic disease at age 50 over the course of 25 years. During that time span, scientists of the study asked all the participants to report how much sleep they got every four to five years for tracking. 

According to results from the study, those who slept five hours or less faced a 30% higher risk for chronic illnesses than those who got at least seven hours of sleep. By age 70, that likelihood for people sleeping less than five hours bumped up to a 40% greater risk. 

"As people get older, their sleep habits and sleep structure change," said Severine Sabia, the lead author of the study and a researcher at the University College London's Institute of Epidemiology and Health, in a news release. 

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The chronic diseases tracked in the study included: diabetes, cancer, coronary heart disease, stroke, heart failure, chronic obstructive pulmonary disease, chronic kidney disease, liver disease, depression, dementia, mental disorders, Parkinson’s and arthritis.

"Short sleep duration in midlife and old age is associated with higher risk of onset of chronic disease and multimorbidity," the study authors wrote. "These findings support the promotion of good sleep hygiene on both primary and secondary prevention by targeting behavioral and environmental conditions that affect sleep duration and quality."

The findings of the study mirror previous research released last week by the US Centers for Disease Control and Prevention that determined older adults who do not receive seven to nine hours of sleep have a far greater chance of developing chronic diseases, as well as obesity and high blood pressure.

How much sleep should I get?

According to National Sleep Foundation guidelines, here's how much we should be sleeping per night:

• New-borns 0 to 3-months old: 14-17 hours
• Babies 4 to 11 months: 12-17 hours
• Children ages 1 to 5: 10-14 hours
• Children ages 6 to 13: 9-11 hours 
• Teens ages 14 to 17:8-10
• Adults 18 to 64: 7-9 hours
• Adults 65+: 7-8 hours

Thank you

World Health Informatics Blog. (community health)

Note :

1) This blog is originally published on 

https://www.usatoday.com/story/news/health/2022/10/25/sleep-study-five-hours-chronic-diseases/10594845002/

2) This Blog is for Education purpose only and not a treatment for any diseases