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Our immune programs weaken as we become older, making fewer cells that battle an infection and assist us get well from sickness and harm. Scientists aren’t utterly certain why. They could have a greater thought now, nevertheless, because of a examine in GeroScience.
“Immune cell changes occur during aging for a number of reasons, but we still don’t completely understand why we have fewer antibody-producing cells with age,” mentioned Leslie Crews, Ph.D., assistant professor of medication at College of California San Diego College of Drugs, co-leader of the Hematologic Malignancies Analysis Program at UC San Diego Moores Most cancers Middle, and a member of the college’s Sanford Stem Cell Institute.
Crews’ lab, in collaboration with researchers at UC Irvine, has discovered that decreased perform of an enzyme known as ELOVL2 (brief for “elongation of very long chain fatty acids-like 2”) hurries up immune system modifications related to getting older.
ELOVL2 performs a important position in synthesizing sure varieties of lipids (fatty compounds), and its abundance is thought to say no with age. Insufficient ELOVL2 modifications the steadiness of lipids in cells, impairing the event of B cells, the lymphocytes (white blood cells) liable for making antibodies to battle off an infection.
The findings counsel that lipid metabolism might play a central position in sustaining a wholesome immune system as we age.
The researchers analyzed gene and protein expression, together with lipid profiles, within the bone marrow of mice whose Elovl2 gene had been inactivated. Earlier research have proven that lowered ELOVL2 perform promotes accelerated getting older in different tissues, however that is the primary to look at the position of the enzyme in getting older immune cells.
When the genetically altered mice have been simply 18–20 months previous, the shortage of ELOVL2 enzymatic exercise decreased the expression of a number of genes associated to B cell improvement of their bone marrow. The truth is, their ELOVL2 exercise was so lowered that it resembled that of a lot older management mice.
The lipid profiles of those mice additionally resembled these of the aged management mice, with low ranges of unsaturated fat in contrast with saturated fat.
“ELOVL2 is a key enzyme necessary for synthesis of the omega−3 fatty acid DHA, one of the main components of all cell membranes,” mentioned co-corresponding writer Dorota Skowronska-Krawczyk, an affiliate professor within the Division of Physiology and Biophysics and the Division of Ophthalmology, and school member within the Middle for Translational Imaginative and prescient Analysis at UC Irvine College of Drugs.
“We believe that DHA keeps the cell membranes in the stem cell precursors of B cells flexible and resilient.”
With ELOVL2 depleted, the mice have been unable to supply as many purposeful B cells as wholesome mice of comparable age.
“This loss was directly linked to changes in fat (lipid) metabolism, causing a complete shift in membrane composition and fluidity, ultimately accelerating immune system aging,” mentioned first writer Silvia Vicenzi, Ph.D., a California Institute for Regenerative Drugs (CIRM) postdoctoral fellow at UC San Diego College of Drugs.
To evaluate the applicability of the mouse research to the human immune system, the researchers analyzed gene expression knowledge from hematopoietic (blood) stem and progenitor cells (HSPCs) from human bone marrow samples collected at numerous ages.
Much like the mouse research, they discovered substantial reductions within the expression of a gene known as CD79B in older people, together with a near-total lack of ELOVL2-expressing HSPCs in individuals greater than 60 years of age.
“The same immune cell population that disappeared in our mutant mouse model was also dramatically reduced in the elderly human population,” Vicenzi mentioned.
With ELOVL2 non-functional, the complement of lipids modifications, negatively affecting the cells liable for preventing infections, based on Crews.
Many trendy diets are low in unsaturated fat, together with necessary omega-3 fatty acids like DHA, the researchers famous. This deficiency can impair immune perform and negatively have an effect on general well being, a number of inhabitants research have proven.
Among the many researchers’ different discoveries: when Elovl2 is not produced correctly, cells are “in a reduced state of metabolic fitness,” Crews mentioned. “What was even more surprising was that a normal diet is not enough to overcome the changes at the genetic level.”
This discovering means that older people could possibly counteract the consequences of age on their immune system by way of precision lipid supplementation tailor-made to their particular wants. Numerous sufferers might probably entry the sort of intervention. However extra analysis is required to find out whether or not the required fatty acids could be efficient when taken orally, or if they might must be delivered by way of one other path to keep away from degradation by the digestive tract, Crews cautioned.
Gene remedy may additionally be value exploring, the researchers famous. In a earlier examine, Skowronska-Krawczyk and her colleagues demonstrated that enhancing Elovl2 gene expression in getting older mice boosted DHA ranges within the eye, leading to enhancements to imaginative and prescient. The researchers plan to research whether or not focusing on ELOVL2 exercise might improve immune perform.
The examine additionally means that lipid metabolism might play a job in blood cancers, with promising implications for the remedy of those ailments.
The CD79B gene and different B cell-related genes affected by ELOVL2 enzymatic exercise (PAX5, IRF4) are ceaselessly mutated or abnormally activated in lymphoid malignancies comparable to lymphoma and a number of myeloma. Given this, therapeutically focusing on the ELOVL2 gene might probably impair most cancers development, based on the researchers.
“We believe that by studying the biology of aging, we can find new therapies to prevent age-related diseases and increase the human health span,” Skowronska-Krawczyk mentioned.
Extra data:
Silvia Vicenzi et al, Systemic deficits in lipid homeostasis promote aging-associated impairments in B cell progenitor improvement, GeroScience (2025). DOI: 10.1007/s11357-025-01594-w
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