The National Institute on Aging, part of the National Institutes of Health, has awarded a grant to researchers at New York University College of Dentistry (NYU Dentistry) to explore age-related, chronic low-grade inflammation and changes in the gut microbiome. The grant (R01AG068857), which began August 15, provides $2.4 million over five years.
Chronic low-grade inflammation that develops with age is known as inflammaging, and it plays an important role in the rate of aging and age-related conditions such as diabetes and heart disease. Inflammaging is likely the consequence of a dysfunctional relationship between an imbalanced gut microbiome and the immune system.
Xin Li, PhD, associate professor of molecular pathobiology at NYU Dentistry and the project’s contact principal investigator, studies metabolites—small molecules that are produced during metabolism—and how they function as signals in aging and other conditions. Li and her colleagues recently found that the elevation of a metabolite called succinate is associated with aging in both humans and mice.
Elevated levels of succinate alter the gut microbiome by increasing the abundance of disease-causing organisms and also activate the succinate receptor to increase inflammation and the production of myeloid lineage in the bone marrow. Preliminary data from Li’s team shows that the interplay among gut microbes, altered metabolites, and the activation of succinate receptor contributes to inflammaging.
In this NIH-funded study, the researchers will examine the impact of succinate elevation on the gut microbiome in animal models and how these changes regulate signaling to promote inflammation. They will then “reprogram” the microbiome using antibiotics and fecal transplants to see if this alters the inflammation. The researchers will also study the role of bone marrow in succinate-stimulated inflammation and the myeloid lineage shift.
“Our study aims to help us better understand how the aging microbiome relates to the causes and pathophysiology of age-related chronic inflammation,” said Li. “If we find that targeting the gut microbiome and succinate receptor activation can alleviate inflammaging, this could provide us with novel targets for treating age-related inflammation.”
Deepak Saxena, PhD, professor of molecular pathobiology at NYU Dentistry, is the project’s multiple principal investigator.
About NYU College of Dentistry
Founded in 1865, New York University College of Dentistry (NYU Dentistry) is the third oldest and the largest dental school in the US, educating nearly 10 percent of the nation’s dentists. NYU Dentistry has a significant global reach with a highly diverse student body. Visit https://dental.nyu.edu for more.
