In aging brains, there are fewer anti-inflammatory molecules

Aging involves complex plot twists and a large number of characters: inflammation, stress, metabolic changes and many others
.
Now, scientists at the Salk Institute and the University of California, San Diego, have identified another factor involved in the aging process — a class of lipids called SGDGs (3-sulfogalactose diacylglycerol), which decrease in the brain with age and may have anti-inflammatory effects
.

The study, published in Nature Chemical Biology and published Oct.
20, 2022, helps unravel the molecular underpinnings of brain aging, uncover new mechanisms of age-related neurological diseases, and provide opportunities
for future therapeutic interventions.

"These SGDGs clearly play an important role in the aging process, and this discovery opens up the possibility of other key pathways of aging that we have been missing," said Frederik Paulsen, professor and chair of the Salk Clayton Foundation Peptide Biology Laboratory, Alan
Saghatelian.
"This is a clear example that should be studied in depth in
the future.
"

SGDGs are a class of lipids
.
Lipids contribute to healthy brain structure, development, and function, while poorly regulated lipids have been linked to
aging and diseased brains.
However, unlike genes and proteins, lipids are poorly understood and are often overlooked
in aging research.
Sagertrian excels at discovering new lipids and determining their structure
.

His lab, in collaboration with Professor Dionicio Siegel of UC San Diego, made three findings on SGDGs: In the brain, lipid levels in older mice are very different from those in younger mice; SGDGs family members and related lipids changed significantly with age.
SGDGs may be regulated
by processes known to regulate aging.

To arrive at these findings, the team took an unusual exploratory approach, combining
large-scale studies of lipids (lipidomics) with structural chemistry and advanced data analysis.
They first obtained lipid profiles
of 5-year-old mouse brains from 1 month to 18 months using liquid chromatography-mass spectrometry.
Technological advances in such instrumentation have dramatically increased the number of data points available to scientists, and advanced data analysis has allowed them to identify age-related patterns
across a large number of lipid profiles.
The team then constructed SGDG molecules and tested them for biological activity
.

"SGDGs were first discovered in the 70s of the 20th century, but there have been few follow-up studies
.
These lipids are largely forgotten in the lipid database
.
No one knew that SGDGs would change or be regulated during aging, let alone that they were biologically active and could be therapeutically targeted," said first author Dan Tan, a postdoc
in Salk Saghatelian's lab.

The analysis showed that SGDGs have anti-inflammatory properties, which may be linked to
neurodegenerative diseases and other neurological disorders associated with increased inflammation in the brain.

The team also found that SGDGs are present in the brains of humans and primates, suggesting that SGDGs may play an important role
in animals other than mice.
Further research is needed to prove whether SGDGs contribute to neuroinflammation
in humans.

In the future, the team will study how SGDGs are regulated with aging and what proteins are responsible for making and breaking them down, which may open the door
to the discovery of new gene activity associated with aging.

Siegel, co-corresponding author of the study, said: "With an improved understanding of the structure of SGDGs and our ability to create them in the laboratory, research on these important lipids is now very open and ripe
for discovery.
"

A class of anti-inflammatory lipids decrease with aging in the central nervous