Enzyme in Lipid Metabolism Connected to Immune System Aging

As individuals age, their immune systems tend to weaken, resulting in fewer cells that combat infections and facilitate recovery from illnesses or injuries. The precise reasons behind this decline remain under investigation, but recent research offers promising insights. A study published in GeroScience by scientists from the University of California San Diego and UC Irvine has identified a key enzyme, ELOVL2, that plays a critical role in this process.

ELOVL2 (elongation of very long chain fatty acids 2) is essential in synthesizing specific lipids—fatty compounds vital for cellular functions. Notably, the activity of ELOVL2 declines with age, leading to imbalances in cellular lipid composition. This imbalance impairs B cell development—the type of white blood cells responsible for producing antibodies, our body's primary defense against pathogens.

The research team analyzed gene and protein expression along with lipid profiles in the bone marrow of genetically modified mice lacking functional ELOVL2. They observed that at 18-20 months—the equivalent of older age in humans—these mice exhibited significant reductions in B cell development markers and lipid profiles resembling those of much older control mice. A deficiency in ELOVL2 disrupted the synthesis of omega-3 fatty acids, particularly DHA, which is fundamental in maintaining flexible and resilient cell membranes.

Further analysis of human bone marrow samples revealed similar patterns: older individuals showed decreased expression of ELOVL2 and related genes, along with a near-total loss of ELOVL2-expressing hematopoietic stem cells. These findings suggest that lipid metabolism, regulated by ELOVL2, is central to preserving immune competence with age.

The study indicates that dietary supplementation with certain fatty acids or gene therapy might counteract this decline. Since diets often lack sufficient omega-3 fatty acids like DHA, nutritional interventions tailored to enhance lipid balance could potentially rejuvenate immune functions in older adults. Additionally, researchers are exploring gene therapy approaches to boost ELOVL2 activity, as previous work demonstrated improvements in vision through such methods.

Beyond immune health, the research highlights possible implications for blood cancers, as genes affected by ELOVL2 activity—such as CD79B—are often mutated or dysregulated in lymphoid malignancies like lymphoma and multiple myeloma. Targeting ELOVL2 could therefore have therapeutic potential in cancer treatment.

Overall, these findings deepen our understanding of how lipid metabolism impacts aging immune systems and open new avenues for interventions aimed at extending health span and reducing age-related disease burden.

For more detailed information, see the original study: Silvia Vicenzi et al, Systemic deficits in lipid homeostasis promote aging-associated impairments in B cell progenitor development, GeroScience (2025). Source: https://medicalxpress.com/news/2025-04-key-enzyme-lipid-metabolism-linked.html