Miller School Study Highlights Role of Immunometabolism in Aging
This study is the first to demonstrate that metabolic abnormalities in immune cells lead to a reduced ability to generate protective immunity.
In an article published in the journal Nature Communications, University of Miami Miller School of Medicine immunology researchers have identified metabolic changes that decrease the body’s immunity as people age.
“It is widely recognized that aging is associated with elevated levels of inflammation and metabolic changes,” said Daniela Frasca, Ph.D., research associate professor of microbiology and immunology at the Miller School and principal investigator of the study. “Our findings have identified and characterized age-associated metabolic changes that may accelerate and/or exacerbate deficiencies in immune cells from older adults, particularly those responsible for diminished secretion of protective antibodies against infections and vaccines.”
A Research First
This study is the first to demonstrate that metabolic abnormalities in immune cells lead to a reduced ability to generate protective immunity. Co-authors include Maria Romero, Kate Miller, Andrew Gelsomini, Denisse Garcia, Kevin Li and Dhananjay Suresh. Miller and Gelsomini joined Dr. Frasca’s lab after taking her Miller School course on inflammation’s impact on the immune system.
The researchers compared the immunometabolic status of B lymphocytes in younger study participants to those of elderly participants. B lymphocytes produce antibodies, and Dr. Frasca and team found a higher metabolic, or glycolytic, status in immune cells correlated with more inflammation and an inhibited ability to generate humoral immunity.
The research team also pinpointed the role a metabolic compound – long thought to be inessential – plays in immunity. Contrary to accepted wisdom, lactate has the ability to induce pathogenic B lymphocyte behavior and increase bodily inflammation.
“The metabolite lactate, the end product of anaerobic glycolysis, which has long been considered a discarded metabolic compound, plays a crucial role in age-associated defects in dysfunctional humoral responses,” Dr. Frasca said. “The effects of lactate, as described in the paper, recapitulate key features of B lymphocytes that infiltrate inflammatory tissues, where lactate-induced signaling may contribute to various pathological features.”
Study Could Lead to New Therapies
Dr. Frasca believes the study has the potential to lead to new treatments that will spur helpful immune responses in the elderly and, thus, assist in warding off disease.
“These findings provide a rationale for the development of new therapies that selectively target metabolic products involved in the generation of inflammatory pathogenic immune cells to improve antibody responses in elderly individuals who are susceptible to infections and/or do not respond adequately to vaccination,” Dr. Frasca said.
The study was initially published to the medRxiv website in August 2023. Subsequently, it was submitted to Nature Communications for peer review and accepted in July 2024.
Tags: aging, Department of Microbiology and Immunology, Dr. Daniela Frasca, immunology