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Apr 21 2025
24As humans age, their immune systems gradually weaken, producing fewer infection-fighting cells and leaving the body more vulnerable to disease. While this phenomenon is well-documented, the underlying causes remain only partially understood. A new study published in GeroScience sheds light on one possible mechanism, pointing to a critical enzyme involved in lipid metabolism—ELOVL2—as a key player in the aging of immune cells.
ELOVL2, short for "elongation of very long chain fatty acids-like 2," plays a crucial role in synthesizing certain lipids, including omega-3 fatty acids. Its activity naturally declines with age. Researchers at the University of California San Diego and UC Irvine discovered that diminished ELOVL2 function accelerates aging processes in white blood cells, particularly B cells, which are essential for producing antibodies.
“Immune cell changes occur with age for many reasons, but we still don’t fully understand why antibody-producing cells decline,” said Leslie Crews, Ph.D., assistant professor of medicine at UC San Diego and co-leader of the Hematologic Malignancies Research Program. Her lab, in collaboration with UC Irvine, focused on how decreased ELOVL2 activity affects lipid balance and immune cell development.
Using genetically modified mice with an inactivated Elovl2 gene, the team analyzed bone marrow samples for gene and protein expression, as well as lipid composition. These mice, though only 18 to 20 months old, exhibited immune profiles resembling those of significantly older control mice. Their lipid profiles showed a notable drop in unsaturated fats and an increase in saturated fats, which correlated with impaired B cell development.
“ELOVL2 is essential for synthesizing the omega-3 fatty acid DHA, a major component of all cell membranes,” explained Dorota Skowronska-Krawczyk, Ph.D., co-corresponding author and associate professor at UC Irvine. “We think DHA helps keep the membranes of B cell precursors flexible and resilient.”
Without sufficient ELOVL2 activity, the mice produced fewer functional B cells. The researchers attributed this reduction to changes in lipid metabolism that altered membrane structure and fluidity, speeding up immune aging.
To determine if the findings applied to humans, the researchers examined gene expression in blood stem and progenitor cells (HSPCs) from people of different ages. They observed a sharp decline in both ELOVL2-expressing HSPCs and the gene CD79B, which is critical for B cell function, in individuals over 60.
“The same immune cell population that vanished in our mouse model was significantly reduced in older humans,” said lead author Silvia Vicenzi, Ph.D., a postdoctoral fellow at UC San Diego.
The study also noted that modern diets often lack sufficient omega-3 fatty acids, potentially worsening the effects of ELOVL2 decline. Even more concerning, Crews pointed out that dietary improvements alone may not reverse the genetic-level damage caused by reduced enzyme activity. “Cells were in a diminished state of metabolic fitness, and a standard diet wasn’t enough to counteract this,” she said.
These insights suggest that targeted lipid supplementation—or even gene therapy—might help restore immune function in aging individuals. Skowronska-Krawczyk's previous work showed that boosting ELOVL2 expression in mice improved vision by increasing DHA levels in the eye, raising hopes for similar benefits in the immune system.
Additionally, the findings may have implications for blood cancer treatment. Several genes affected by ELOVL2 activity, including CD79B, PAX5, and IRF4, are frequently mutated in lymphoid cancers like lymphoma and multiple myeloma. Targeting ELOVL2 could open new avenues for cancer therapies.
“By studying aging biology, we can uncover therapies to prevent age-related diseases and enhance the human healthspan,” Skowronska-Krawczyk concluded.
Source:https://www.sciencedaily.com/releases/2025/04/250418112813.html
This is non-financial/medical advice and made using AI so could be wrong.
