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Aging is a major risk factor for neurodegenerative diseases and can lead to cognitive decline
.
Genome-wide gene expression studies reveal conserved pathways of brain aging, such as mitochondrial dysfunction, stress response, and inflammatory response
.
Lipids play a vital role in many biological processes, especially in the brain
.
Lipids make up more than half of the brain's dry weight and are essential
for the healthy development of the brain.
Impaired lipid metabolism in the brain is associated with
neurological disorders in the elderly.
SGDG (3-Sulfogalactodecanylglycerol) is a class of lipids that contribute to the maintenance of healthy brain structure, development, and function, however, unlike genes and proteins, lipids are not well understood and are often overlooked
in aging research.
Recently, scientists from the Clayton Foundation Peptide Biology Laboratory in the United States published an article entitled "A class of anti-inflammatory lipids decrease with aging in the central nervous system" in the journal Nature Chemical Biology, which found that the gradual loss of SGDGs with age leads to neuroinflammation in the elderly brain.
This ultimately leads to pathological changes
associated with aging.
To determine the effects of aging on lipids in mouse brains, the researchers conducted an LC-MS/MS-based non-targeted lipidomics study to compare multiple lipids in the brains
of 4-, 12-, 25-, 48-, and 78-week-old mice.
These mice correspond to juvenile, adult, middle-aged and old animals
.
Compositional analysis (PCA) of identified lipids showed that brain samples were separated primarily based on age, suggesting that lipid components underwent continuous remodeling
throughout the mice's lifespan.
The researchers then identified these unlabeled lipids as sulfonosylglycerol lipids, which are further divided into sulfonosyldiacylglycerol and sulfonylalkyl acylglycerol
.
A total of 8 sulfonyldiacylglycerol and 12 sulfonylalkyl acylglycerol were identified, with 6 subclasses in each subclass in the black module
.
Enrichment analysis showed that sulfonyldiacylglycerol, sulfonylalkyl acylglycerol and MGDGs were highly enriched in this module, indicating that they were co-regulated or functionally related
.
Some early studies have shown that SGDGs are present in rat brains, abundant in developing rat brains, and subsequently decreased
in levels in young adult rats.
In the serum and 13 tissues tested (brain, spinal cord, testes, ovaries, adipose tissue, intestines, kidneys, liver, pancreas, spleen, lungs, heart, and muscles), SGDG levels in the spinal cord were found to be about ten times higher than in the brain, and steadily decreased
as the mice aged.
However, SGDG levels in the testicles do not change
with age.
Similarly, sulfogalactoyl acylglycerol (SGAAG) levels in the brain and spinal cord decline, but are not affected by aging in the testes, where they are most abundant
.
These results suggest that metabolic regulation of SGDGs and SGAAGs is tissue-specific
.
Taken together, this is the first study to show that a class of aging-associated central nervous system lipids exert anti-inflammatory effects, and the findings suggest that the gradual decrease in the content of SGDGs with age leads to neuroinflammation in the elderly brain, which ultimately leads to age-related pathological changes
.
Further research is needed to determine whether administration of SGDGs can inhibit neuroinflammation in vivo, and further mechanisms by
which SGDGs inhibit the production of pro-inflammatory cytokines.
These studies will provide insights
for the development of new therapies to treat inflammation and age-related diseases.
Dan Tan, first author of the study: "SGDG was first identified in the 70s of the 20th century, but follow-up studies are rare
.
These lipids are largely forgotten and are nowhere to be found
in the lipid database.
No one knows that SGDGs change or be regulated during aging, let alone that they are biologically active and may be treatable targets.
"
Saghatelian, corresponding author of the paper: "These SGDGs clearly play an important role in aging, and this discovery opens up the possibility of other key pathways
to aging that we have been missing.
This is a fairly obvious case, and it should be dug more in the
future.
"
Original source:
Tan, D.
, Konduri, S.
, Erikci Ertunc, M.
et al.
A class of anti-inflammatory lipids decrease with aging in the central nervous system.
Nat Chem Biol (2022).
https://doi.
org/10.
1038/s41589-022-01165-6.