Researchers Fight Cellular Senescence, Low-Grade Inflammation

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AMSTERDAM—Low-grade inflammation in older adults can impede immune responsiveness, and researchers have shed light on how this happens. They have developed a short-term treatment that blocks inflammation and boosts the immune response, an expert said at EULAR: the Annual European Congress of Rheumatology.

The findings were presented in a session on cellular senescence related to inflammation and rheumatic diseases that also included new findings on how targeting a certain protein could help reverse senescence in chondrocytes and help osteoarthritis patients.

Low-Level Inflammation

As people age, inflammation develops at low levels, not as high as that seen in rheumatic diseases, but with effects nonetheless, said Arne Akbar, PhD, professor of immunology at University College London and associate of the Institute of Healthy Aging. This can result in reactivation of viruses that someone had already developed immunity to, such as chickenpox. This immune senescence tends to result from DNA damage caused by reactive oxygen species, ionizing radiation or ultraviolet radiation, Dr. Akbar said.

“Senescence is there to prevent cells with damaged DNA from proliferating,” Dr. Akbar said. If the cells did spread, there would be a risk of malignancy.

In a second phase, the cell attempts to repair the damage, using a cluster of proteins around damaged areas. If the repairs are made, the cell can go back to its normal functions. But if not, in a third stage, kinases are activated, leading to growth arrest of the damaged cells.

Dr. Akbar

“Senescent cells are not just useless cells that sit around doing nothing,” Dr. Akbar said. “They’re actually quite inflammatory,” bringing on a phenomenon known as inflammaging. “They secrete a whole range of inflammatory mediators, and that’s thought to be because [the body is] trying to get the immune system to come along and eradicate those cells or to get some tissue remodeling associated with damage in those cell types.”

The researchers in the Akbar group have found a clear divide in the response to immune skin challenges between younger and older subjects. But they have found this isn’t due to a lower number of memory T cells, but seems to be because of differences in the skin environment. They have also found the accumulation of senescent fibroblasts in the skin during aging is correlated with lower clinical scores on immune skin challenges.¹

Dr. Akbar’s team wondered: Is there a way to block this inflammation and bring about a more robust immune response?

As people age, an inflammation develops at low levels, not as high as tha t seen in rheumatic diseases, but with effects nonetheless, said Arne Akbar, PhD.

Losmapimod Study

In recent work, the researchers injected older adults with varicella zoster vaccine (VZV), measured the immune response and assigned a clinical score.² Two to three months later, they treated patients with the p38 mitogen-activated protein (MAP) kinase inhibitor losmapimod, followed by another VZV injection four days later, and another clinical score was calculated.