Graduate School (PhD): University of Tokyo, Japan
Post-Docotral Research: Baylor College of Medicine, Houston, TX
- Aging is associated with reduced stress tolerance. Elderly people become very sick and often die by mild injury, surgery or infection, which is not serious for younger people. I have been trying to understand the mechanisms for such age-dependent vulnerability to physiological stresses by using mouse models of aging.
- Research projects in our laboratory have centered on the development of clinically relevant animal models of inflammatory diseases in which old animals exhibit significantly elevated disease severity and mortality compared to young animals. Using these models, we have been working to reveal underlying physiological/molecular mechanisms for age-dependent disease severity.
- Our current projects involve elucidating the roles of visceral white adipose tissues in age-dependent severity of sepsis and acute pancreatitis. Another active ongoing project is to understand the molecular mechanisms of physiological dysfunction after recovery from severe sepsis. For this study, we developed a new murine sepsis-resuscitation model that exhibit a long-term muscle weakness among mice that survived severe sepsis.
NIH R01 AG055359 "Mechanisms mediating severity of acute pancreatitis in the aged" (PI)
NIH R01 GM126181 "Chronic muscle weakness in sepsis survivors" (PI)
NIH R01 AG039732 "The role of adipose tissue in age-dependent sensitivity to critical illnesses" (PI)
NIH F31 GM117868 "Analysis of chronic muscle weakness in post-septic mice using a novel resuscitation protocol" Steele (PI), Saito (Mentor)
Steele AM, Starr ME, & Saito H. Late therapeutic intervention with antibiotics and fluid resuscitation allows for a prolonged disease course with high survival in a severe murine model of sepsis. Shock, 47(6):726-734 (2017)
Starr ME, Steele AM, Cohen DA, & Saito H. Short-term dietary restriction rescues mice from lethal abdominal sepsis and endotoxemia, and reduces the inflammatory/coagulant potential of adipose tissue. Critical Care Medicine 44: e5090519 (2016).
Starr ME, Saito M, Evers BM, & Saito H. Age-associated increase in cytokine production during acute systemic inflammation – II: The role of IL-1β in age-dependent IL-6 production in adipose tissue. Journal of Gerontology Biological Sciences 70(12):1508-1515 (2015)
Starr ME, Takahashi H, Okamura D, Mrazek AA, Ueda J, Stromberg AJ, Evers BM, Esmon CT, & Saito H. Increased coagulation and suppressed generation of activated protein C in aged mice during intra-abdominal Sepsis. American Journal of Physiology -Heart and Circulatory Physiology 308: H83-H91 (2015)
Starr ME & Saito H. Sepsis in old age: Review of human and animal studies. Aging and Disease 5(2):126-136 (2014)
Starr ME, Hu Y, Stromberg A, Carmical JR, Wood TG, Evers BM, & Saito H. Gene expression profile of mouse white adipose tissue during inflammatory stress: age-dependent upregulation of major procoagulant factors. Aging Cell 12: 194-206 (2013)
Okamura D, Starr ME, Stromberg A, Lee EY, Evers BM, & Saito H. Age-dependent vulnerability to experimental acute pancreatitis is associated with increased systemic inflammation and thrombosis. Aging Cell 11: 760-769 (2012)
Starr ME, Ueda J, Yamamoto S, Evers BM, & Saito H. The effects of aging on pulmonary oxidative damage, protein nitration and extracellular superoxide dismutase down-regulation during systemic inflammation. Free Radical Biology & Medicine 50: 371-380 (2011)
Starr ME, Ueda J, Takahashi H, Weiler H, Esmon CT, Evers BM, & Saito H. Age-dependent vulnerability to endotoxemia is associated with reduction of anti-coagulant factors activated protein C and thrombomodulin. Blood 115: 4886-4893 (2010)
Starr ME, Evers BM, & Saito H. Age-associated increase in cytokine production during systemic inflammation: Adipose tissue as a major source of IL-6. Journal of Gerontology Biological Sciences 64: 723-730 (2009)
Ueda J, Starr ME, Takahashi H, Du J, Chang L-Y, Crapo JD, Evers BM, & Saito H. Decreased pulmonary extracellular superoxide dismutase during systemic inflammation. Free Radical Biology & Medicine 45: 897-904 (2008)
- Steele, AM ; Starr, ME ; Saito, H. "Late Therapeutic Intervention with Antibiotics and Fluid Resuscitation Allows for a Prolonged Disease Course with High Survival in a Severe Murine Model of Sepsis." Shock (Augusta, Ga.) 47, 6 (2017): 726-734. [PubMed Link] | [ Full text ]
- Starr, ME ; Steele, AM ; Cohen, DA ; Saito, H. "Short-Term Dietary Restriction Rescues Mice From Lethal Abdominal Sepsis and Endotoxemia and Reduces the Inflammatory/Coagulant Potential of Adipose Tissue." Critical care medicine 44, 7 (2016): e509-19. [PubMed Link] | [ Full text ]
- Starr, ME ; Takahashi, H.; Okamura, D.; Zwischenberger, BA ; Mrazek, AA ; Ueda, J.; Stromberg, AJ ; Evers, BM ; Esmon, CT ; Saito, H. "Increased coagulation and suppressed generation of activated protein C in aged mice during intra-abdominal sepsis." American journal of physiology. Heart and circulatory physiology 308, 2 (2015): H83-91. [PubMed Link] | [ Full text ]
- Starr, ME ; Saito, M.; Evers, BM ; Saito, H. "Age-Associated Increase in Cytokine Production During Systemic Inflammation-II: The Role of IL-1β in Age-Dependent IL-6 Upregulation in Adipose Tissue." The journals of gerontology. Series A, Biological sciences and medical sciences 70, 12 (2015): 1508-15. [PubMed Link] | [ Full text ]
- Shinozaki, S.; Chang, K.; Sakai, M.; Shimizu, N.; Yamada, M.; Tanaka, T.; Nakazawa, H.; Ichinose, F.; Yamada, Y.; Ishigami, A.; Ito, H.; Ouchi, Y.; Starr, ME ; Saito, H.; Shimokado, K.; Stamler, JS ; Kaneki, M. "Inflammatory stimuli induce inhibitory S-nitrosylation of the deacetylase SIRT1 to increase acetylation and activation of p53 and p65." Science signaling 7, 351 (2014): ra106. [PubMed Link] | [ Full text ]
- Starr, ME ; Saito, H. "Sepsis in old age: review of human and animal studies." Aging and disease 5, 2 (2014): 126-36. [PubMed Link] |
- Starr, ME ; Steele, AM ; Saito, M.; Hacker, BJ ; Evers, BM ; Saito, H. "A new cecal slurry preparation protocol with improved long-term reproducibility for animal models of sepsis." PloS one 9, 12 (2014): e115705. [PubMed Link] | [ Full text ]
- Starr, ME ; Hu, Y.; Stromberg, AJ ; Carmical, JR ; Wood, TG ; Evers, BM ; Saito, H. "Gene expression profile of mouse white adipose tissue during inflammatory stress: age-dependent upregulation of major procoagulant factors." Aging cell 12, 2 (2013): 194-206. [PubMed Link] | [ Full text ]
- Mustain, WC ; Starr, ME ; Valentino, JD ; Cohen, DA ; Okamura, D.; Wang, C.; Evers, BM ; Saito, H. "Inflammatory cytokine gene expression in mesenteric adipose tissue during acute experimental colitis." PloS one 8, 12 (2013): e83693. [PubMed Link] | [ Full text ]
- Okamura, D.; Starr, ME ; Lee, EY ; Stromberg, AJ ; Evers, BM ; Saito, H. "Age-dependent vulnerability to experimental acute pancreatitis is associated with increased systemic inflammation and thrombosis." Aging cell 11, 5 (2012): 760-9. [PubMed Link] | [ Full text ]
- Starr, ME ; Saito, H. "Age-related increase in food spilling by laboratory mice may lead to significant overestimation of actual food consumption: implications for studies on dietary restriction, metabolism, and dose calculations." The journals of gerontology. Series A, Biological sciences and medical sciences 67, 10 (2012): 1043-8. [PubMed Link] | [ Full text ]
- Wang, X.; Mandal, AK ; Saito, H.; Pulliam, JF ; Lee, EY ; Ke, ZJ ; Lü, J.; Ding, S.; Li, L.; Shelton, BJ ; Tucker, T.; Evers, BM ; Zhang, Z.; Shi, X. "Arsenic and chromium in drinking water promote tumorigenesis in a mouse colitis-associated colorectal cancer model and the potential mechanism is ROS-mediated Wnt/β-catenin signaling pathway." Toxicology and applied pharmacology 262, 1 (2012): 11-21. [PubMed Link] | [ Full text ]
- Takahashi, H.; Okamura, D.; Starr, ME ; Saito, H.; Evers, BM "Age-dependent reduction of the PI3K regulatory subunit p85α suppresses pancreatic acinar cell proliferation." Aging cell 11, 2 (2012): 305-14. [PubMed Link] | [ Full text ]