Khadeja Rizvi
Research Mentor: Hsiao Hsin Sung
Mentor Department: UMSOD, Dentistry
Author(s): Khadeja Rizvi, Isabella Park, Parker Ng, Zayan Tariq, Alison Lock, Pranaya Sripathi, Alex Stryk, Ali Abdo, Hsiao Hsin Sung
Session: Session 3 (11:00 AM – 11:50 AM)
Presentation Type: Poster 36
Abstract
The aging process can be defined by the emergence of a chronic, low-intensity inflammatory state known as “inflammaging.†Inflammaging is the driving pathogenesis for neurodegeneration, metabolic dysfunction, and more age-related disorders. Recent research found that Interleukin-11 (IL-11) was a key regulator of the cytokine that promotes the inflammaging through signal nodes such as mTOR and JAK-STAT3. Previous studies have found that restricting the IL-11 signaling pathway leads to improved health and life span in animals. This study investigated the hypothesis that the lifespan-extending effects of the drug Canagliflozin (Cana) are correlated with systemic alteration in IL-11 signaling pathways. We used UM-HET3 mice, a genetically heterogeneous model, and treated them with Cana starting at 16 months of age. The survival analysis revealed a significant sexual dimorphism: Cana treatment resulted in an extension of lifespan in male mice. However, it led to a reduction in female lifespans. We performed a molecular analysis of live and adipose tissue and found that the male mice’s IL-11 signaling pathway was consistently inhibited. Though the IL-11 protein levels in the liver remained the same, distinct changes were observed in specific adipose depots like the perigonadal adipose tissue. Here, the IL-11 protein levels were found to decrease in the male mice that lived longer, but it was increased in the female mice, correlating directly with the observed survival outcomes. These findings suggest that the geroprotective effects of Cana are partially mediated by the reduction of the IL-11 driven inflammaging. The data highlights the critical need to consider sex-specific responses in pharmacological interventions that target aging and cytokine signaling networks
