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Blood Lipidome Profiles Linked to Aging, Health Measures in Quantitative Study

NEW YORK – A team from Stanford University and other centers in the US has tracked the composition and levels of lipids in the blood of hundreds of individuals, uncovering relationships to health, disease, aging, and metabolic traits.

"In comparison to the human genome, the human lipidome is poorly understood," co-first author Daniel Hornburg, a former postdoctoral researcher in senior author Michael Snyder's genetics lab at Stanford, said in an email.

"Lipids are more than just energy storage — they're vital for cell structure, signaling, and metabolism," Hornburg explained. "By comprehending the complexities of lipids, we can better understand human biology, [as well as] enhance treatments and preventative strategies."

As they reported in Nature Metabolism on Monday, the researchers reasoned that it may be possible to pinpoint potential biomarkers of aging, inflammation, disease onset, or disease progression, along with clues to the biological mechanisms behind these processes, by following lipid profiles in individuals' blood samples over time.

Nevertheless, they explained, lipid features found in the blood and other parts of the body can reflect features intrinsic to individuals, but also their diet, lifestyle, microbial community composition, life stage, and health status.

Lipids "are involved in pretty much everything," Snyder said in a statement, "but because they're so heterogenous, and there are so many of them, we probably don't know what most lipids really do."

Using a high-throughput quantitative lipidomics pipeline that included triple-quadrupole mass spectrometry (MS) and differential mobility separation, the researchers profiled 846 lipid species spanning a range of lipid subclasses in more than 1,500 blood plasma samples collected at multiple time points over two to nine years in 112 participants as they aged and naturally transitioned between bouts of health and disease, including insulin resistance, which can presage type 2 diabetes.

The team collected samples at three-month intervals when the individuals were healthy, but also looked at samples taken every few days when participants experienced notable health events.

"We shed light on health issues like inflammation, metabolic diseases, and aging and specific lipids that could act as early disease markers, provide insights into disease progression, and aid in crafting personalized treatments," Hornburg said.

When they analyzed the lipidomic data alongside published genomic, transcriptomic, proteomic, metabolomic, and 16S ribosomal RNA-based microbiome measurements available for the participants, the team tracked complex lipid subclass changes that coincided with typical aging as well as those that accompanied acute or chronic diseases ranging from viral infection to cancer or metabolic conditions.

Among other results, the team found that lipid signatures — including age-related declines in omega-3 fatty acids and increases in cholesterol — tended to vary from one individual to the next.

Even so, the investigators saw some consistent lipid patterns that were associated with specific health or disease states. In particular, they found that ether-linked phosphatidylethanolamines, a group of cell signaling lipids with a suspected antioxidant role, tended to coincide with insulin sensitivity and other positive health measures.

The work "raises the interesting question of whether lipid profiles could predict whether an individual is biologically aging more quickly or more slowly," co-first author Si Wu, a postdoctoral researcher in Snyder's Stanford lab, said in a statement.

In individuals with insulin resistance, on the other hand, the researchers documented altered relationships between lipids and clinical markers, along with immune-related changes and faster-than-usual shifts in certain age-related lipids, even after controlling for other factors linked to insulin resistance such as body mass index.

While hundreds of lipid species turned up at higher- or lower-than-usual levels in blood samples from participants infected with a respiratory virus, the infection-related lipid changes differed between individuals with or without insulin resistance, hinting at metabolic health effects on infection responses.

Such results "could have major implications for how we manage diseases such as [COVID-19], as understanding these changes could help us predict disease progression or devise new therapeutic strategies to promote recovery and perhaps mitigate devastating morbidities such as long COVID," Hornburg said.

More broadly, the lipidome findings point to the potential for changing viral infection outcomes or health more generally by tweaking an individual's lipid levels through dietary or other interventions — a possibility that is yet to be explored directly.

"Our findings reveal dynamic changes in the plasma lipidome during respiratory viral infection, insulin resistance, and aging, suggesting that lipids may have roles in immune homeostasis and inflammation regulation," the authors reported, noting that "future studies should explore how altering the exogenous lipid intake (for example, through diet) or targeting lipid conversion enzymes can affect both plasma lipid signatures and clinical phenotypes such as [insulin resistance], acute and chronic inflammation, and molecular aging."