Inhibiting a certain microRNA may be a way to keep our bodies healthier as we grow older, scientists say. In a mouse study, the team used an antagomir (a microRNA inhibitor) specifically designed to block microRNA-141-3p, whose levels are significantly elevated with age. When they examined the mice afterwards, they found a more youthful profile throughout their bodies.
The team believes their findings suggest reducing this microRNA’s expression is a possible strategy to improve immune, bone, and muscle health with age.
The study appeared in Aging and Disease.
MicroRNAs are small (18–25 nucleotides), noncoding RNAs that help regulate gene expression. Several, including microRNA-141-3p, have been implicated in aging’s effects, such as increasing levels of potentially damaging chronic inflammation and shrinking muscle mass.
In 2018, this team reported that with age, expression of microRNA-141-3p goes up while the key signaling molecule stromal cell derived factor 1 (SDF-1), which helps stem cells make healthy bone and muscle, goes down in both human and mouse mesenchymal stem cells.
In this latest study, which the researchers believe is the first of its kind, the team used an antagomir to block microRNA-141-3p in aged mice. Antagomirs are currently restricted to research, but may have therapeutic value for patients, said the study’s senior author, Sadanan Fulzele, DVM, PhD, aging researcher in the Department of Medicine at the Medical College of Georgia at Augusta University.
The mice, who would equate to humans in their 60s, were treated for three months with twice-weekly subcutaneous injections of this antagomir.
The scientists then looked at changes that occurred in the blood, bone, muscle, and the spleen, whose tasks include regulating levels of infection-fighting white blood cells. They found a more youthful profile in all these systems.
In the spleen, for example, they saw more inflammation-reducing immune cells called rather than their inflammation-promoting counterpart. The blood also had lower levels of inflammation-promoting cytokines, and the microstructure of the bone was more solid, while muscle fiber size was bigger.
The researchers also found that microRNA-141-3p regulates expression of AUF1, a “good” gene whose many jobs include regulating the stability of messenger RNA.
AUF1 helps protect younger people from making so many proinflammatory products, such as IL-6, that contribute to chronic, damaging inflammation. It does the same for cell senescence when cells become less able to function normally and divide but typically don’t die. Higher levels of microRNA-141-3p mean less of the protective AUF1. Blocking the microRNA led to higher levels and consequently less inflammation and senescence.
With age, the repair/replacement capacity of cells is known to decrease so that, for example, bone loss begins to outpace new bone formation. Meanwhile inflammation, essential to healing but destructive at chronic, high levels, creeps upward. Resulting problems can range from increasing physical frailty to an increased incidence of diseases like cancer, cardiovascular disease, and dementia.
The team notes that their work is geared toward preventing damage, rather than trying to restore a healthy normal. Some of their next planned steps include looking at how blocking the microRNA impacts other age-related concerns like cognition and giving the microRNA-141-3p-specific antagomir for a longer period.
