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October 08, 2025
Researchers at The Ohio State University Wexner Medical Center and College of Engineering are using novel non-viral gene therapy technology to gain insight into how to treat age-related heart disease. They found that adding more brown fat or increasing the level of a fat molecule, or lipokine, released by energy-burning brown fat helps preserve heart health.
“One of the biggest things we see with aging is cardiovascular disease, which increases dramatically in patients who are over 65. Now we’re correlating it to a decrease in the lipokine 12,13-diHOME, and we’re showing directly that when we increase this lipokine that we can essentially rescue cardiac function,” said Kristin Stanford, professor in the Department of Surgery at the College of Medicine and associate director of the Dorothy M. Davis Heart and Lung Research Institute.
Co-authored by Biomedical Engineering Professor Daniel Gallego-Perez, results of the research were published recently in the journal Nature Communications.
Brown fat is one of two types of fat in humans and other mammals. Sometimes called “good” fat, it differs from ordinary white fat in that it burns energy and generates heat via a process called thermogenesis.
In the study, researchers analyzed blood samples from young and older humans as well as mice and found 12,13-diHOME levels decrease with age for both males and females. They discovered transplanting brown fat from young mice into older ones improved cardiovascular function. Previous Ohio State research showed that exercising increased the levels of 12,13-diHOME, helping protect the heart.
Looking for a way to stimulate the release of the lipokine without exercise, scientists used tissue nanotransfection (TNT), a non-viral gene therapy, to increase it in older male and female mice.
“In just six weeks, we were able to really negate a lot of the effects of cardiovascular aging by using TNT to increase 12,13-diHOME. The results were quite striking with improvements to ejection fraction and the heart’s pumping cycles,” said Gallego-Perez, director of Advanced Nanotherapeutics at the Gene Therapy Institute and lead inventor of TNT.
Researchers also discovered that 12,13-diHOME can directly block a protein called CaMKII, which is important for controlling calcium in heart cells. This helps explain how 12,13-diHOME might help keep the heart working well as it ages.
“Older adults are the fastest-growing demographic in the world and at the greatest risk of developing heart disease, the leading cause of death worldwide," Stanford said. "More than 20% of the U.S. is projected to be over the age of 65 by the year 2030 so new technologies like what we’re looking into are vital for combatting heart disease later in life.”