Top
Washington University in St. Louis - School of Medicine
Department of Developmental Biology

Shin-ichiro Imai, M.D., Ph.D.

Professor

Washington University School of Medicine
Campus Box 8103
660 South Euclid Avenue, Rm 362A, McDonnell Science Bldg.
St. Louis , MO 63110
(314) 362-7228

Links

Research Interests

My laboratory studies the systemic control of aging and longevity in mammals. To dissect such a complex network for mammalian aging/longevity control, our lab has addressed the following three questions:


1) Are there any dominant organs/tissues that regulate the process of aging and longevity in mammals?


2) How do these "control centers" communicate with other organs/tissues to control aging and longevity in mammals?


3) What signaling pathways or molecules regulate such communications at a systemic level?


We are particularly focusing on the tissue-specific functions of the mammalian NAD+-dependent deacetylase SIRT1, a key mediator that coordinates various metabolic responses in multiple tissues, and NAD+ biosynthesis mediated by nicotinamide phosphoribosyltransferase (NAMPT), a critical pacemaker that comprises a novel circadian regulatory feedback loop through the regulation of Sirt1 activity in peripheral tissues.


Most recently, we have obtained critical clues to these three questions from our study on brain-specific SIRT1-overexpressing (BRASTO) transgenic mice. We have clearly demonstrated that BRASTO mice exhibit a significant delay in the aging process and extension of life span in both males and females. SIRT1-dependent neural activation in the dorsomedial and lateral hypothalamic nuclei (DMH and LH, respectively) protects against age-related declines in skeletal muscle mitochondrial function, physical activity, body temperature, oxygen consumption, and quality of sleep. SIRT1 and its novel partner Nk2 homeobox 1 (Nkx2-1) regulate these physiological functions through the upregulation of orexin type 2 receptor (Ox2r) expression in the DMH and LH, and their colocalization identifies a specific subset of neurons in these hypothalamic regions. These findings provide critical insight into the importance of hypothalamic SIRT1 and also suggest a fundamental role of the hypothalamus as a high-order “control center of aging” in the systemic regulation of mammalian aging and longevity.


Currently, we have three main projects: 1) The function of the hypothalamus as a "control center of aging" in mammals. We are trying to characterize a novel subset of neurons in the DMH and LH, the Sirt1/Nkx2-1-double positive neurons, to better understand Sirt1-mediated aging/longevity control in mammals. 2) The importance of skeletal muscle as an "effector" to control the process of aging. Skeletal muscle responds to the stimulation that the hypothalamus mediates through the sympathetic nervous system. We are interested in this intertissue communication between the hypothalamus and skeletal muscle. 3) Systemic regulation of mammalian NAD+ biosynthesis. We are currently studying systemic NAD biosynthesis mediated by intra- and extracellular nicotinamide phosphoribosyltransferase (iNampt and eNampt). We speculate that adipose tissue functions as a "modulator" for aging/longevity control in mammals. Understanding the system dynamics of these intertissue communications among the hypothalamus, skeletal muscle, and adipose tissue will allow us to develop an intervention to control the process of aging, and even longevity, in mammals.

 

Selected Publications

  • Ramsey, K. M.§, Yoshino, J.§, Brace, C. S.§, Abrassart, D., Kobayashi, Y., Marcheva, B., Hong, H.-K., Chong, J. L., Buhr, E. D., Lee, C., Takahashi, J. S., Imai, S.*, and Bass, J.*  (2009)  Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis.  Science  324: 651-654.  (§equally contributing authors, *Co-correspondence)  PMCID: PMC2738420

 

For a complete list of Dr. Imai's publications, click here

Axol Bio

Shin-ichiro Imai, M.D., Ph.D.

Professor

Washington University School of Medicine
Campus Box 8103
660 South Euclid Avenue, Rm 362A, McDonnell Science Bldg.
St. Louis , MO 63110
(314) 362-7228

Links

Other Information

Education and Professional Experience

  • Professor
    Department of Developmental Biology
    Department of Medicine (Joint)
    Washington University School of Medicine, 2013-present
  • Associate Professor (tenured), Department of Developmental Biology, Department of Medicine (joint), Washington University School of Medicine, 2008-2013
  • Assistant Professor, Department of Developmental Biology (Formerly, Molecular Biology and Pharmacology), Department of Medicine (joint), Washington University School of Medicine, 2001-2008.
  • Postdoctoral Fellow/Associate, Massachusetts Institute of Technology, Department of Biology, 1997-2001.
Postdoctoral Adviser: Dr. Leonard Guarente
  • Instructor, Keio University School of Medicine, Department of Microbiology, 1993-1997.
  • Ph.D., Keio University Graduate School of Medicine, Tokyo, Japan, 1995. Thesis Supervisor: Dr. Toshiya Takano
  • M.D., Keio University School of Medicine, Tokyo, Japan, 19

Honors and Awards

  • 2013   Vincent J. Cristofalo, PhD, Annual Lectureship, Institute on Aging, University of Pennsylvania
  • The Ellison Medical Foundation Senior Scholar in Aging Award, 2008-2012
  • The Longer Life Foundation Pilot & Feasibility Award, 2008-2010
  • WUSM 2008 Distinguished Investigator Award, 2007
  • The Glenn Award for Research in Biological Mechanisms of Aging, 2007-2008
  • The Juvenile Diabetes Research Foundation Innovation Award, 2006-2007
  • The American Diabetes Association Innovation Award, 2006-2008
  • Special Recognition for Excellence in Mentoring in the 7th Annual Outstanding Faculty Mentor Awards, 2006
  • Washington University Clinical Nutrition Research Unit (CNRU) Pilot & Feasibility Award, 2005-2007
  • The Ellison Medical Foundation New Scholar in Aging Award, 2003-2007
  • Washington University Center for Aging Pilot Project Award, 2002
  • Leukemia & Lymphoma Society Special Fellowship, 2001-2004
  • Medal from the Tokyo Society of Medical Sciences and Faculty of Medicine, Tokyo University, Japan, 2000