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by Elise Wachspress

Recent research shows that the average age of death for those past 65 continues to increase steadily, by about 3 years over each generation (25 years). This is good news if you are over 65, but even better news if you are still in diapers—you can probably expect to add another 8 or 9 years to current life expectancy, once you make it to age 65.

Ah, the pessimists will say, but does that only mean more years of physical decline, progressive frailty, cognitive impairment?

Maybe not. The Duchossois Family Institute was founded on the idea that scientific research can help us live not only longer lives, but healthier, more vibrant lives.

Eugene Chang, MD, and Sebastian Pott, PhD, have laid out a research plan to see how the microbiome might make old(er) age healthier and more vital. They note that the gut microbiome—the largest organ in the human body—has been implicated in health problems (diabetes, autism, autoimmune diseases) known to strike in youth or middle age. But there has been little study of how the microbiome affects the aging process, and vice versa.

The few studies that have been done seem to show older people have a less diverse microbial population living in their guts. What causes this? Diet, environmental factors, lifestyle? Already a team of scientists at UChicago has demonstrated that the microbiome is likely a factor in Alzheimer’s disease, and they are working to better understand the mechanisms involved. But what about aging itself?

Because studying the microbiome in humans presents significant technical and ethical problems, Chang and Pott want to investigate these connections in that standard model of laboratory discovery, the mouse.

Using young and old mice of the same strain, living in the same kind of environment, the team will first examine the actual cells in the guts of each. They will look for any differences in the genes active in these cells and corresponding “epigenetic” changes—changes caused by differences in the chemical groups attached to the DNA molecules. These added chemical groups can sometimes act as on/off switches, activating or de-activating particular proteins and genes, with significant effects on how the biochemistry in a person’s body plays out.

Pott has special expertise in “single-cell genomics;” he can analyze large numbers of individual cells at once. Single-cell technology can assess the epigenetic changes in each particular cell, rather than the “average” across a whole population of cells, helping the team identify differences between young and old mice and obtain a “molecular age” of cells, even if they are measurable only in some cells.

Next, the team will compare fecal samples from young and old mice to monitor the differences in the bacteria in the guts of each. They will then transplant the fecal samples into germ-free mice and see how the microbial communities harvested from young and old mouse-donors affect the health of their new hosts.

In the third experiment, they will use gut cells from young and old mice to grow organoids— three-dimensional, multi-cellular tissues that mimic the mouse’s actual gut tissue. The team can then assess the differences between tissue grown from young and old mice, how these tissues differ from those grown in actual mice, and how microbial components affect the apparent age of the cells in these cultures.

The team is looking for funding for this early-stage, high-risk, high-reward project, the kind that rarely receives funding from the National Institutes of Health. But what they learn can provide many insights into how aging affects and is affected by the microbes we carry in our bodies—and open up whole new areas of preventive medicine.

Chang and Pott hope their work will help make the extra three years we are gaining in every generation full of energy and vigor.

Elise Wachspress is a senior communications strategist for the University of Chicago Medicine & Biological Sciences Development office