by Buck Institute

Buck Faculty Henri Jasper, PhD, Receives Prestigious BIG Award

Henri Jasper is becoming increasingly convinced that having a healthy gut is key to living a long and healthy life.  The Glenn Foundation and the American Federation for Aging Research (AFAR) have awarded him their prestigious “Breakthroughs in Gerontology” (BIG) award to help him prove his point.

Jasper’s research has already reaped great benefits for fruit flies, which share many of the same microbes that we humans have in our digestive systems.  He and his team improved health and lengthened lifespan in the flies by altering the symbiotic relationship between bacteria and the absorptive cells lining the fly intestines.

Sponsored by the Glenn Foundation for Medical Research in collaboration with AFAR, the two-year, $200,000 BIG award is designed to provide timely support to a small number of research projects that are building on early discoveries that show translational potential for clinically relevant strategies, treatments and therapeutics that address human aging and healthspan. “AFAR and the Glenn Foundation are excited that Henri’s work will continue to contribute discoveries to the field of age-related research through this award,” notes Stephanie Lederman, Executive Director of AFAR.

Aging takes a toll on the gut, and Jasper’s research is providing a model for studying many of the dysfunctions that come along with it.  Excessive growth of certain bacteria becomes more common with age and can lead to pain, bloating and weight loss. Bacterial overgrowth may also lead to decreased absorption of certain nutrients, such as folic acid, iron and calcium.  While the list of age-related diseases associated with changes in gut bacteria include cancer, diabetes and inflammatory bowel disease, Jasper says that up to this point there has been no systemic understanding of how we go from having a young healthy gut to one that is decrepit.

Image of fly intestines: the nuclei are stained blue and intestinal cell structures are in green, with associated blood cells in red.[/caption]

“Our work looks at oxidative stress, inflammation, impaired immune response and the over-proliferation of stem cells,” says Jasper.  “We have been able to put the changes into a hierarchical, causal relationship and highlight the points where we can intervene to restore the right balance of microbes in the gut.” Specifically, Jasper’s team showed that changes in the way gut tissue defends against bacteria during aging result in an inability to control both healthy and unhealthy bacteria levels, leading to a buildup of these normally helpful microbes and an overactive immune response that leads to sickening of gut tissue. Changing the activity of one gene brought both the number of bacteria and the health of the tissue back to levels seen in a young animal and extended the lifespan of the fly.

“I am very grateful to AFAR and the Glenn Foundation for their support,” says Jasper. “If we can understand how aging affects the bacterial population in the gut – first in the fly and then in humans  –  our data suggests that we should be able to make a strong impact on human healthspan.”

The immediate plans for the work include characterizing not just changes in the amount of bacteria present in aging guts, but changes in the composition of the microbiome.  They will then  challenge the flies with specific mixtures of bacteria to identify whether there are “good” and “bad” guys in the gut. Furthermore, the lab will pursue genetic studies to characterize the molecular changes to the innate immune system of the aging fly intestine in more detail.  In the long term, the team would like to test the relevance of their findings in flies to mice, and eventually to identify drugs that can reproduce the reduction in the deleterious bacterial load in aging flies and increase their lifespan. Such drugs might also be useful interventions in higher organisms, including humans.

Science is showing that while chronological aging is inevitable, biological aging is malleable. There's a part of it that you can fight, and we are getting closer and closer to winning that fight.

Eric Verdin, MD, Buck Institute President and CEO

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