737A Poster - 12. Physiology, metabolism and aging
Thursday April 07, 2:00 PM - 4:00 PM

Authors:
Luana Machado ¹; Sofia Rosa ¹; Sarah Shnayder ¹; Jim Crott ²; Mitch McVey ¹

Affiliations:
1) Tufts University, Medford, MA; 2) Human Nutrition Research Center on Aging, Boston, MA

Keywords:
a. stress responses; d. intestinal stem cells

The term “inflammaging” has been accepted as an all-encompassing term for the age-related increase in inflammation that occurs in organisms. Inflammaging causes many negative impacts on health and lifespan and is associated with cancer progression. Interestingly, some bacteria have been shown to have anti-inflammatory properties. One example is the obligate anaerobe Parabacteroides distasonis (Pd), which was recently shown to decrease cancer incidence and progression in a mouse colon cancer model through the modulation of systemic inflammation.
Because inflammation has been linked to aging and decreased health, we explored the effects of Pd treatment on lifespan and healthspan in a Drosophila model system. We found that chronic administration of Pd in the food of adult flies extends the mean lifespan of two genetically distinct strains by 19% and 28% in males and females respectively. In addition, consumption of Pd promotes the maintenance of climbing ability in a negative geotaxis assay, suggesting that Pd also promotes healthy aging.

Having established the impact of Pd on lifespan and healthspan, we began our search for the molecular mechanism through which this bacteria is acting. We first explored its effect on gut membrane stability through Smurf assays, a qualitative approach to examining gut leakage by analyzing how much blue dye diffuses from the intestinal tract into the abdomen of the flies. By comparing dye leakage among treatment groups, we observed that Pd reduces gut barrier defects and increases gut stability in flies as they age.

Given these findings, we hypothesized that Pd could maintain gut membrane integrity in flies by impacting the expression and localization of smooth septate junction proteins (tight junction protein homologs) in the gut, decreasing systemic inflammation, or indirectly preventing hyperproliferation of intestinal stem cells. We conducted q-RT-PCR on candidate genes related to these processes. Our results suggest that expression of inflammatory markers and proteins required for smooth septate junction formation increases with age, but their levels are not affected by treatment with Pd. Analysis using RNA-Seq is ongoing. We are also using fluorescent imaging to visualize potential physical differences among gut tissue of varying treatment groups, specifically looking at stem cell proliferation patterns and smooth septate junction formation. Identification of conserved molecular pathways through which Pd exerts its effects could have therapeutic applications in humans.