Link Between Inflammation and Aging Discovered

A new Yale-led study may help scientists slow down aging and prevent the onset of chronic disease.

Although there has long been evidence demonstrating connections between inflammation and declining health in the elderly, the specific link between the two has remained unclear. Yale professor of comparative medicine Vishwa Deep Dixit and researchers at Pennington Biomedical Research Center showed that knocking out the Nlrp3 molecule in mice prevented the loss of cell function induced by inflammation. This sensor is the missing link in showing how the effects of aging spread through inflammation. This discovery also holds promise for slowing down the process of aging by reducing the immune response, which may lead to a lower risk of age-related disease, said study author Donald K. Ingram, a professor of neuroscience at the Pennington Biomedical Center.

“[This] will help us understand potentially what goes wrong as we age, and maybe altering some of those pathways will help us understand how to better treat immune processes in someone who is over 65,” said Yale professor of laboratory medicine Stephanie Eisenbarth, who was not involved in the study.

Researchers tested their hypothesis that Nlrp3 — a molecule known to play a role in the inflammatory pathway — mediates inflammation and disease onset in mice. The knockout reduced inflammation and prevented decline in cognition, bone density and immune response.

The results demonstrate that the Nlrp3 molecule is a key component that controls age-related inflammation, Ingram said.

“The implications are if we can find ways of controlling this internal sterile inflammatory pathway through some pharmacologic means, it might affect our [aging] philosophy,” Ingram said.

The results show the molecule has a profound impact on a range of age-related disorders, said Yale professor of immunobiology and rheumatology Martin Kriegel.

Clifford Rosen, another lead researcher on the study and a physician at the Maine Medicine Center, found the results “both novel and provocative,” and hopes to have opportunities to pursue this research in larger animals and eventually humans.

Though the results are promising, it will take further research to determine the full effects of disrupting the Nlrp3 molecule, said Laura McCabe, a physiology professor at Michigan State and a researcher on the study. Disrupting the pathway may lead to unintended side effects since the Nlrp3 molecule effects all inflammatory responses and not just those related to age. Researchers will take this next step before moving on to possible pharmaceutical applications.

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