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More than a ‘gut feeling’ on cause of age-associated inflammation

McMaster study could improve intestinal health, immune function in older adults

White blood cell macrophages isolated from mice. The ability of macrophages from old mice to bind and destroy bacteria was impaired due to age-associated inflammation. When the inflammation was reduced, their ability to defend against bacteria improved.

Gut microbes cause age-associated inflammation and premature death in mice, McMaster University researchers have found. The study could lead to new strategies to improve intestinal health and immune function in older adults.

The research, published today in Cell Host & Microbe, shows that imbalances in the composition of gut microbes in older mice cause the intestines to become leaky, releasing bacterial products that trigger inflammation, impair immune function and reduce lifespan.

Humans with high levels of inflammatory molecules are more likely to be frail, hospitalized, and less independent. They are also more susceptible to infections, chronic conditions such as dementia and cardiovascular disease and death.

Up until now, the cause of the relationship between the composition of gut microbes and inflammation and poor health in the elderly has not been determined.

“To date, the only things you can do to reduce your age-associated inflammation are to eat a healthy diet, exercise and manage any chronic inflammatory conditions to the best of your ability,” said senior author Dawn Bowdish, a professor of pathology and molecular medicine at McMaster, and member of the Michael G. DeGroote Institute for Infectious Disease Research.

“We hope that in the future we will be able use drugs or pre- or probiotics to increase the barrier function of the gut to keep the microbes in their place and reduce age-associated inflammation and all the bad things that come with it.”

Bowdish and her colleagues raised mice in germ-free conditions and compared them to their conventionally raised counterparts. In contrast to conventionally raised mice, the germ-free mice did not show age-related increases in inflammation and a higher proportion of them lived to a ripe old age.

Age is associated with an increase in levels of pro-inflammatory cytokines, such as tumor necrosis factor (TNF), in the bloodstream and tissues. It was found that germ-free mice did not have increased TNF with age.

In addition, TNF-deficient mice that did not develop age-associated inflammation or conventional mice that were treated with an anti-TNF drug approved for humans had reduced age-related changes in the microbiome.

“We assume that if we reduce inflammation, we improve immune function. If we improve immune function, we maintain the ability to farm a healthy gut microbiota, but we don’t know for sure yet,” Bowdish explained.

“We also believe that targeting age-associated inflammation will improve immune health and we are investigating repurposing drugs that are already on the market and developing novel strategies or therapeutics to this effect.”

The study was supported by grants from the Canadian Institutes for Health Research (CIHR) and an Early Researcher Award from the Ontario Ministry of Research and Innovation.