Alexander Voorhees
Pronouns: He/Him
Research Mentor(s): Xinna Li
Research Mentor School/College/Department: Pathology / Medicine
Program:
Authors: Alexander Voorhees, Leanne Mercier, Xinna Li
Session: Session 5: 2:40 pm – 3:30 pm
Poster: 98
Abstract
This research aims to investigate alterations in multiple tissues of PTEN transgenic mice (Ptentg mice), known for exhibiting enhanced energy expenditure, reduced adiposity, improved insulin sensitivity, and an extended lifespan in response to high-fat feeding and various interventions. The study focuses on deciphering changes in the brain, muscle, liver, macrophage, and adipocyte status present in Ptentg mice. Notably, similar alterations have been observed in models with mutations (Ames, Snell, GHR-KO, or PAPPA-KO), caloric restriction (CR), and treatment with rapamycin (Rapa), acarbose (Aca), 17aE2, and canagliflozin (Cana). The identified physiological changes include increased uncoupling protein UCP1 in brown and white adipose tissue, shifts in fat-associated macrophage subsets (reducing inflammatory cytokine production), elevated muscle fibronectin type III domain containing 5 (FNDC5) and its cleavage product, irisin (influencing fat cell differentiation), enhanced hepatic GPLD1 production, and elevated hippocampal BDNF and DCX indicative of neurogenesis. The research hypothesizes that Ptentg mice also exhibit a distinct set of changes across multiple tissues, determined by western blot and protein analysis. Furthermore, this study delves into inflammation status in the liver, bone marrow, spleen, lung, and lymph nodes of slow-aging mice. Chronic inflammation associated with aging is examined through the lenses of molecular and cellular inflammation. Molecular inflammation, primarily orchestrated by the NF-?B signaling pathway, involves the upregulation of proinflammatory genes (TNF-a/ß, ILs, and adhesion molecules). Cellular inflammation manifests as M1/M2 macrophage polarization, contributing to age-related chronic conditions. The research investigates M1/M2 polarization, along with levels of TNF-a, IL-6, IL-1ß, CRP, and serum amyloid A in various tissues of slow-aging mice models subjected to mutations, caloric restriction, and interventions like rapamycin, acarbose, 17aE2, and canagliflozin. This comprehensive analysis aims to provide insights into the intricate interplay between genetic, dietary, and pharmacological interventions in modulating inflammation during the aging process for slow-aging mice; its results may be applicable to other models.
