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Declining anti-inflammatory molecules may play key role in brain aging

Researchers have discovered a unique type of fat molecule in the brain may have anti-inflammatory effects and play a crucial role in preventing age-related neurological disease. Animal studies demonstrate levels of the molecule decline with age and their absence could contribute to brain inflammation associated with age-related neurodegeneration.

Several decades ago scientists discovered a novel class of lipids in rat brains, dubbed SGDGs (3-sulfogalactosyl diacylglycerols). At the time a few studies revealed these SGDGs seemed to play a role in developing rat brains, and then decrease in quantity as the animals grow older.

But by the end of the 1970s researchers had all but forgotten about SGDGs. They were never established as being present in human brains and were relegated to a footnote in animal molecule databases.

“SGDGs were first identified in the 1970s, but there were few follow-up studies," explained first author on the new study Dan Tan. "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."

The new research from Tan and colleagues never set out to specifically study SGDGs. Instead, the initial focus was to conduct a broad investigation of lipid changes in mouse brains as they age.

In conducting this investigation the researchers discovered SGDGs progressively decrease in mouse brains over the course of the animal's entire lifespan. The research also showed the age-related decline in SGDGs occurred specifically in the animal's central nervous system.

The next step of the research involved synthesizing SGDGs and exploring their biological role. In lab tests the researchers found SGDGs possess anti-inflammatory properties, suggesting their age-related decline could influence neurodegenerative disease.

The final part of the study was to work out whether SGDGs are actually present in the human brain. The last time this was investigated, in 1978, SGDGs were not detected. However, analytical techniques have evolved since then and using new technology the study found, for the first time, evidence of SGDGs in both human and primate brains.

"To our knowledge, this is the first study showing that a class of aging-related CNS lipids exerts anti-inflammatory effects," the researchers concluded in the study. "Our findings suggest that the progressive loss of SGDGs with age contributes to neuroinflammation in the aged brain, eventually leading to pathological changes associated with aging."

Alan Saghatelian, co-corresponding author on the study, has a particular research focus on lipids. He believes lipids are a profoundly understudied area in aging research, and while more work will certainly need to be done to establish the implications of declining SGDGs in humans, these findings are good evidence these fat molecules are worthy of investigation.

“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 Saghatelian. “This is a pretty clear case of something that should be dug into more in the future.”

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