The result is that “immune cells may no longer respond properly.”
Normally, inflammation is the body’s normal response to fight pathogens or to remove damaged cells from our tissues. Once the immune cells have reached their goal, the infection is over, the wound is healed, and the inflammation subsides. Aging-related chronic inflammation, however, is not local. The immune system ramps up its overall activity, producing a chronic, low-grade inflammation. This is often called “inflammaging.”
“Inflammaging is also related to cancer development—because in inflamed tissue we see increased cell proliferation," said Neri.
Neri and other researchers found that on a molecular level inflammation in older mice was characterized by the upregulation of a set of genes that encode receptors of the innate immune system.
This upregulation eventually results in the activation of genes that produce inflammatory cytokines, as well as activating Stat1, a master protein responsible for regulating genes associated with inflammation. The process serves as a feedback loop that maintains the inflammatory state.
In mice that were given 30 percent less food between 4 to 22 months of age—essentially most of the mice’s life—and mice fed 30 percent less for only two months at the end of their lives, researchers found that diet restriction had positive effects on all organs studied except for the heart.
Turning Off the Genetic 'SOS Signal'Scientists also hope to identify points for future drug therapies for aging-related chronic inflammation.
"Within this regulatory network we describe, one well-studied and important component is, for example, TLR4, a gene that encodes a receptor of the innate immune system," said Seyed Mohammad Mahdi Rasa, one of the key researchers in the study.
"The receptor acts like an SOS signal that we don't need when there are no pathogens to fight. If we could downregulate TLR4, we would be able to reduce the chronic inflammatory response in aging," he added.
While dietary restriction “appears to change” the composition of microorganisms in the digestive tract, which in turn reduces inflammaging, Neri said that it remains to be seen whether vitamins or probiotics will produce a similar effect.
“If it is possible to change the intestinal flora of the microbiome through dietary supplements, the same beneficial effects could be achieved without the need for a restricted diet," Neri added. "We first need a better understanding of the processes involved."