Interim Department Chair
Charles E Wood
- Mailing Address:
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PO Box 100274
GAINESVILLE FL 32610
- Physical Address:
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1345 Center Drive RM M556
DEPARTMENT OF PHYSIOLOGY AND FUNCTIONAL GENO
GAINESVILLE FL 32610
- 2022 PLoS pathogens
- 2022 American journal of physiology. Regulatory, integrative and comparative physiology
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2022
Organocatalyst treatment improves variant calling and mutant detection in archival clinical samples.Scientific reports
- 2022 Journal of clinical medicine
- 2022 Toxicology reports
- 2022 Frontiers in oncology
- 2022 American journal of physiology. Regulatory, integrative and comparative physiology
- 2022 Toxicology
- 2021 Scientific reports
- 2021 Toxicology and applied pharmacology
- 2021 Toxicology and applied pharmacology
- 2021 Cancer prevention research (Philadelphia, Pa.)
- 2021 Toxicology and applied pharmacology
- 2021 Journal of virology
- 2021 Metabolites
- 2021 Journal of toxicologic pathology
- 2020 AIDS (London, England)
- 2020 Viruses
- 2020 The Journal of physiology
- 2020 The Journal of infectious diseases
- 2020 International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
- 2020 Drug metabolism and disposition: the biological fate of chemicals
- 2020 BMC pregnancy and childbirth
- 2020 Toxicological sciences : an official journal of the Society of Toxicology
- 2020 Physiological genomics
- 2020 Toxicology reports
- 2020 Scientific reports
- 2020 PLoS pathogens
- 2020 Critical reviews in toxicology
- 2020 Toxicologic pathology
- 2019 Inhalation toxicology
- 2019 Molecular cancer research : MCR
- 2019 The Journal of infectious diseases
- 2019 mBio
- 2019 Journal of virology
- 2019 PloS one
- 2019 American journal of physiology. Endocrinology and metabolism
- 2019 Scientific reports
- 2019 Toxicological sciences : an official journal of the Society of Toxicology
- 2019 International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
- 2019 Frontiers in physiology
- 2019 Toxicological sciences : an official journal of the Society of Toxicology
- 2019 Applied and environmental microbiology
- 2019 American journal of physiology. Regulatory, integrative and comparative physiology
- 2019 American journal of physiology. Regulatory, integrative and comparative physiology
- 2019 Clinical pediatrics
- 2019 Toxicological sciences : an official journal of the Society of Toxicology
- 2019 Toxicological sciences : an official journal of the Society of Toxicology
- 2018 Journal of medical virology
- 2018 Current HIV research
- 2018 Inhalation toxicology
- 2018 Journal of medical virology
- 2018 PLoS pathogens
- 2018 PLoS pathogens
- 2018 Frontiers in physiology
- 2018 The Journal of physiology
- 2018 Toxicologic pathology
- 2018 The Journal of physiology
- 2018 Toxicologic pathology
- 2018 Toxicological sciences : an official journal of the Society of Toxicology
- 2018 Genome announcements
- 2018 American journal of physiology. Regulatory, integrative and comparative physiology
- 2018 Toxicology letters
- 2018 Physiological reports
- 2018 Environmental science & technology
- 2017 Archives of virology
- 2017 Environmental health perspectives
- 2017 Journal of medical virology
- 2017 Infectious agents and cancer
- 2017 Regulatory toxicology and pharmacology : RTP
- 2017 Virologica Sinica
- 2017 Scientific reports
- 2017 Scientific reports
- 2017 AIDS (London, England)
- 2017 Journal of medical virology
- 2017 Toxicological sciences : an official journal of the Society of Toxicology
- 2017 Toxicological sciences : an official journal of the Society of Toxicology
- 2017 Frontiers in microbiology
- 2017 The Journal of infectious diseases
- 2017 Toxicological sciences : an official journal of the Society of Toxicology
- 2016 PloS one
- 2016 F1000Research
- 2016 Molecular cancer research : MCR
- 2016 Journal of medical virology
- 2016 Journal of medical virology
- 2016 Particle and fibre toxicology
- 2016 Toxicological sciences : an official journal of the Society of Toxicology
- 2016 The Journal of physiology
- 2016 Cancer prevention research (Philadelphia, Pa.)
- 2016 Physiological reports
- 2016 Physiological reports
- 2016 Clinical & experimental metastasis
- 2016 Toxicologic pathology
- 2016 Toxicological sciences : an official journal of the Society of Toxicology
- 2016 Toxicological sciences : an official journal of the Society of Toxicology
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2016
Genomic Effect of Triclosan on the Fetal Hypothalamus: Evidence for Altered Neuropeptide Regulation.Endocrinology
- 2016 Toxicological sciences : an official journal of the Society of Toxicology
- 2015 Journal of virology
- 2015 Reproductive Sciences
- 2015 Inhalation toxicology
- 2015 Toxicologic pathology
- 2015 Physiological genomics
- 2015 EBioMedicine
- 2015 International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
- 2015 Carcinogenesis
- 2015 Reproductive Sciences
- 2015 Neonatology
- 2015 Toxicological sciences : an official journal of the Society of Toxicology
- 2015 Physiological reports
- 2015 Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
- 2015 International journal of cancer
- 2015 Toxicology and applied pharmacology
- 2015 Reproductive Sciences
- 2015 Reproductive Sciences
- 2015 Reproductive Sciences
- 2015 Journal of the National Cancer Institute
- 2015 Journal of cancer therapy
- 2015 Comprehensive Physiology
- 2015 Environmental science & technology
- 2014 Physiological genomics
- 2014 Reproductive Sciences
- 2014 BMC genomics
- 2014 Physiological genomics
- 2014 Carcinogenesis
- 2014 Viruses
- 2014 Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
- 2014 Physiological reports
- 2014 Reproductive Sciences
- 2014 Reproductive Sciences
- 2014 BMC infectious diseases
- 2014 Regulatory toxicology and pharmacology : RTP
- 2014 PloS one
- 2014 Toxicological sciences : an official journal of the Society of Toxicology
- 2014 American journal of physiology. Regulatory, integrative and comparative physiology
- 2014 Journal of virological methods
- 2014 Advances in experimental medicine and biology
- 2014 Toxicologic pathology
- 2014 Toxicological sciences : an official journal of the Society of Toxicology
- 2014 Viruses
- 2013 PloS one
- 2013 Toxicologic pathology
- 2013 Breast cancer research : BCR
- 2013 Pediatric Research
- 2013 The FASEB's Journal
- 2013 The FASEB's Journal
- 2013 Journal of virology
- 2013 PloS one
- 2013 Physiological genomics
- 2013 PloS one
- 2013 Pediatric Research
- 2013 International journal of cancer
- 2013 Cancer prevention research (Philadelphia, Pa.)
- 2013 Clinical obstetrics and gynecology
- 2013 American journal of physiology. Regulatory, integrative and comparative physiology
- 2013 Toxicologic pathology
- 2013 Retrovirology
- 2013 Journal of immunotoxicology
- 2013 Menopause (New York, N.Y.)
- 2012 The FASEB's Journal
- 2012 The FASEB's Journal
- 2012 The Journal of cardiovascular nursing
- 2012 The Journal of general virology
- 2012 PloS one
- 2012 Menopause (New York, N.Y.)
- 2012 Physiological genomics
- 2012 Journal of agricultural and food chemistry
- 2012 Emerging infectious diseases
- 2012 The FASEB's Journal
- 2012 Breast cancer research and treatment
- 2012 Toxicologic pathology
- 2012 Toxicologic pathology
- 2012 Toxicological sciences : an official journal of the Society of Toxicology
- 2012 The Journal of nutrition
- 2011 American journal of epidemiology
- 2011 Chemico-biological interactions
- 2011 Reproductive Sciences
- 2011 Reproductive Sciences
- 2011 Reproductive Sciences
- 2011 Reproduction, fertility, and development
- 2011 Reproductive Sciences
- 2011 Endocrinology
- 2011 Cancer research
- 2011 Reproductive sciences (Thousand Oaks, Calif.)
- 2011 Reproductive sciences (Thousand Oaks, Calif.)
- 2011 Pediatric research
- 2011 Neonatology
- 2010 Placenta
- 2010 Environment international
- 2010 AIDS research and human retroviruses
- 2010 PloS one
- 2010 BMC infectious diseases
- 2010 Journal of neurovirology
- 2010 Reproductive Sciences
- 2010 American journal of physiology. Regulatory, integrative and comparative physiology
- 2010 Reproductive Sciences
- 2010 Virology
- 2010 Neuroscience letters
- 2010 Clinical cancer research : an official journal of the American Association for Cancer Research
- 2010 Virology
- 2009 Breast cancer research and treatment
- 2009 Virology
- 2009 Gene expression patterns : GEP
- 2009 The Laryngoscope
- 2009 Menopause (New York, N.Y.)
- 2009 Virology
- 2009 The Journal of general virology
- 2009 American journal of physiology. Regulatory, integrative and comparative physiology
- 2009 Gene expression patterns : GEP
- 2009 American journal of primatology
- 2009 AIDS (London, England)
- 2009 Reproductive Sciences
- 2009 Neonatology
- 2009 American journal of physiology. Regulatory, integrative and comparative physiology
- 2009 American journal of physiology. Regulatory, integrative and comparative physiology
- 2009 Reproductive Sciences
- 2008 Toxicologic pathology
- 2008 Nutrition journal
- 2008 Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
- 2008 Reproductive Sciences
- 2008 American journal of physiology. Endocrinology and metabolism
- 2008 Journal of the National Cancer Institute
- 2008 Reproductive Sciences
- 2008 Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
- 2008 Neuroscience letters
- 2008 Toxicologic pathology
- 2008 Journal of virology
- 2008 AIDS (London, England)
- 2008 Neuroendocrinology
- 2008 Endocrinology
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2008
Cerebral hypoperfusion increases estrogen receptor abundance in the ovine fetal brain and pituitary.Neuroendocrinology
- 2008 Menopause (New York, N.Y.)
- 2008 Clinical and vaccine immunology : CVI
- 2008 The Journal of endocrinology
- 2008 American journal of epidemiology
- 2008 Laboratory investigation; a journal of technical methods and pathology
- 2008 Reproductive Sciences
- 2008 Gene expression patterns : GEP
- 2007 Tropical medicine & international health : TM & IH
- 2007 BMC infectious diseases
- 2007 The Journal of cardiovascular nursing
- 2007 Carcinogenesis
- 2007 Western journal of nursing research
- 2007 Toxicologic pathology
- 2007 Experimental physiology
- 2007 Journal of virology
- 2007 American journal of physiology. Regulatory, integrative and comparative physiology
- 2007 Journal of virology
- 2007 Breast cancer research and treatment
- 2007 American journal of physiology. Regulatory, integrative and comparative physiology
- 2007 Psychoneuroendocrinology
- 2007 Menopause (New York, N.Y.)
- 2006 Retrovirology
- 2006 Cancer research
- 2006 Neuroendocrinology
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2006
Effects of high-dose soy isoflavones and equol on reproductive tissues in female cynomolgus monkeys.Biology of reproduction
- 2006 Fertility and sterility
- 2006 Nutrition and cancer
- 2006 Physiological genomics
- 2006 American journal of physiology. Regulatory, integrative and comparative physiology
- 2006 Clinical cancer research : an official journal of the American Association for Cancer Research
- 2006 Journal of the Society for Gynecologic Investigation
- 2005 American journal of physiology. Regulatory, integrative and comparative physiology
- 2005 Experimental biology and medicine (Maywood, N.J.)
- 2005 Peptides
- 2005 Brain research
- 2005 Journal of the Society for Gynecologic Investigation
- 2005 Breast disease
- 2005 American journal of physiology. Regulatory, integrative and comparative physiology
- 2005 Journal of the Society for Gynecologic Investigation
- 2005 Journal of medical virology
- 2005 Journal of the Society for Gynecologic Investigation
- 2005 AIDS (London, England)
- 2005 American journal of physiology. Regulatory, integrative and comparative physiology
- 2005 Retrovirology
- 2004 Maturitas
- 2004 Journal of virology
- 2004 The Journal of infectious diseases
- 2004 Fertility and sterility
- 2004 The Journal of clinical endocrinology and metabolism
- 2004 The Journal of clinical endocrinology and metabolism
- 2004 The Journal of endocrinology
- 2003 The American surgeon
- 2003 The Journal of infectious diseases
- 2003 Journal of the American College of Cardiology
- 2003 Brain research
- 2003 American journal of physiology. Lung cellular and molecular physiology
- 2003 Brain research
- 2003 Endocrinology
- 2003 Journal of the Society for Gynecologic Investigation
- 2003 The Journal of physiology
- 2002 The Journal of biological chemistry
- 2002 AIDS research and human retroviruses
- 2002 The Journal of physiology
- 2001 Regulatory peptides
- 2001 American Journal of Physiology-Regulatory Integrative and Comparative Physiology
- 2000 Journal of the American College of Cardiology
- 1999 American journal of physiology. Regulatory, integrative and comparative physiology
- 1999 American Journal of Physiology
- 1998 Regulatory peptides
- 1997 Prostaglandins
- 1995 Nursing Research
- 1995 Journal of Endocrinology
- 1995 Reproduction Fertility and Development
- 1993 American Journal of Physiology-Regulatory Integrative and Comparative Physiology
- 1993 Journal of Applied Physiology
- 1993 American Journal of Physiology-Regulatory Integrative and Comparative Physiology
- 1993 American Journal of Physiology-Regulatory Integrative and Comparative Physiology
- 1993 American Journal of Physiology-Endocrinology and Metabolism
- 1992 Journal of Developmental Physiology
- 1992 Circulation
- 1992 American Journal of Physiology-Regulatory Integrative and Comparative Physiology
- 1992 American Journal of Physiology-Regulatory Integrative and Comparative Physiology
- 1992 American Journal of Physiology-Heart and Circulatory Physiology
- 1991 Domestic Animal Endocrinology
- 1991 American Journal of Physiology-Regulatory Integrative and Comparative Physiology
- 1991 American Journal of Physiology
- 1991 American Journal of Physiology-Endocrinology and Metabolism
- 1991 Journal of Developmental Physiology
- 1991 American Journal of Physiology-Regulatory Integrative and Comparative Physiology
- 1991 American Journal of Physiology-Regulatory Integrative and Comparative Physiology
- 1991 Journal of Applied Physiology
- 1991 American Journal of Physiology-Endocrinology and Metabolism
- 1991 American Journal of Physiology-Regulatory Integrative and Comparative Physiology
- 1990
- 1990 American Journal of Physiology
- 1984 Endocrinology
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Apr 2017
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Mar 2020
Therapeutic use of dichloroacetate in treatment of perinatal mitochondrial deficiency and cardiac dysfunctionNATL INST OF HLTH NICHD · Co-Investigator
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Dec 2016
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Nov 2022
Effects of maternal cortisol on perinatal cardiac metabolism and functionNATL INST OF HLTH NICHD · Co-Investigator
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Feb 2016
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Jan 2019
Modeling the Fetal MicrobiomeNATL INST OF HLTH NIAID · Principal Investigator
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Aug 2013
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Jun 2020
DSR Matchng Support-Multidisciplinary Training Program in Hypertension -pj 104297UF DIV OF SPONSORED RES MATCHING FUNDS · Principal Investigator
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Jul 2013
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Jun 2020
Multidisciplinary Training Program in HypertensionNATL INST OF HLTH NHLBI · Principal Investigator
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Nov 2012
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Nov 2019
EIJI Research FundUF FOUNDATION · Principal Investigator
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Feb 2012
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Jan 2019
Fetal Cardiovascular and Endocrine Reflex ResponsesNATL INST OF HLTH NICHD · Principal Investigator
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Aug 2011
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Feb 2020
Corpus Luteal Contribution to Maternal Pregnancy Physiology and Outcomes in ARTNATL INST OF HLTH NICHD · Project Manager
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Sep 2010
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Dec 2020
Physiology New Techniques**UF FOU UNRESTRICTED DONATION · Principal Investigator
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Jun 2010
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May 2016
Short-Term Training in Biomedical Research for Under-Represented MinoritiesNATL INST OF HLTH · Principal Investigator
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Dec 2008
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Dec 2015
Effects of Maternal Cortisol on Fetal and Neonatal Growth and Metabolism.NATL INST OF HLTH NICHD · Project Manager
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Feb 2006
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Jan 2021
Cade ProfessorshipUF FOUNDATION · Principal Investigator
Department Faculty
Stephen Anton Ph.D.

Sudeshna A Chatterjee
David J Clark Sc.D.
I am the Associate Chief of Staff for Research Service (“Chief of Research”) at the North Florida / South Georgia Veterans Health System, and Professor in the UF Department of Neurology. My research focuses on enhancing walking function in people with neurological impairments, particularly older adults and people post-stroke. Ongoing studies involve neurorehabilitation, neuroimaging, non-invasive brain stimulation, electrophysiology, and biomechanics. Grant funding listed below includes only projects administered by UF. For a full listing (including funding from the US Dept of Veterans Affairs) please see the attached curriculum vitae. Publications from my lab group are available at the following links for Pubmed and Google Scholar.
Sung Min Han Ph.D.
Dr. Han completed his B.S. education in Biotechnology in the Republic of South in 2000. He completed three years of military service in the Republic of Korea Air Force. During master’s training from 2001 to 2003 under the mentorship of Dr. Hyeon-Sook Koo at Yonsei University, South Korea, Dr. Han investigated the role of mitochondria in aging using the nematode C. elegans as a genetic and in vivo model animal. He completed his Ph.D. training in 2012 under the mentorship of Dr. Michael Miller at the University of Alabama at Birmingham Medical School. During his Ph.D. training, he continued to use C. elegans to investigate novel signaling mechanisms that link abnormal mitochondrial function to the mechanisms of amyotrophic lateral sclerosis, a neurodegenerative disorder characterized by a progressive loss of motor neurons. After training in a neurodegenerative disorder, Dr. Han became interested in understanding how the nervous system can restore its function after damage. To this end, Dr. Han joined Dr. Marc Hammarlund’s lab at Yale University to investigate the molecular and cellular mechanisms underlying axon regeneration after neuronal injury. Dr. Han joined the University of Florida in 2018 as an Assistant Professor. He is the Course Director of GMS6893 – Clinical and Translational Science Seminar Series, GMS6622 – Mitochondrial Biology in Aging and Disease, and GMS6771 – Clinical Neuroscience of Aging.
My long-term research goal is to understand (i) how the nervous system retains its function and integrity throughout its lifespan and (ii) how it affects organismal aging and health. My current research goals are to investigate:i) how aging neurons regulate mitochondrial dynamics and localization in response to local demand and injury; ii) how mitochondria control nuclear gene expression in two key conditions, including aging and injury; iii) how mitochondria respond to environmental stress and affect organismal aging and health; iv) how mitochondria stress in the nervous system modulate organismal lifespan and healthspan. We utilize the nematode C. elegans as a powerful genetic and in vivo model to answer these questions.
Christiaan Leeuwenburgh Ph.D.
Christiaan Leeuwenburgh received his PhD from the University of Illinois, Urbana-Champagne in 1995 where his doctoral work focused on the regulation of glutathione homeostasis during chronic glutathione deficiencies and/or supplementation. He completed postdoctoral studies in Internal Medicine, Division of Geriatrics and Gerontology and Division of Atherosclerosis, Nutrition and Lipid Research at Washington University School of Medicine, Saint Louis. He became an Assistant Professor in 1998 at the University of Florida and the Director of the Biochemistry of Aging Laboratory. He was promoted to Associate Professor in 2002, Professor in 2007. In 2005 he joined the newly created Department of Aging and Geriatric Research, College of Medicine and Institute on Aging at the University of Florida. He functioned as the the Chief of the Division of Biology of Aging for the Department. Dr. Leeuwenburgh has joint faculty appointments in the Departments of Anatomy and Cell Biology, Biochemistry and Molecular Biology and a member of the department’s doctoral research faculty of the College of Medicine. Dr. Leeuwenburgh’s major research focus is to understand the molecular mechanism of iron homeostasis, oxidative stress and ferroptosis with age . He is conducting research on the role of iron deregulation, ferroptosis, and inflammation in the loss of human skeletal muscle with age and it’s role in human frailty. He has participated in NIH workshops focused on the biology of aging and geriatric research of the National Institute on Aging. He has published papers in Cell, JAMA, The Journal of Biological Chemistry, American Journal of Physiology and Science. In 2004 he received the Nathan Shock Award from the National Institute on Aging. He received the Merck Geriatric Cardiology Research Award from the Society of Geriatric Cardiology in 1999; the National Research Service Award of the NIH from the National Institute on Aging in 1997 and 1998; a Young Investigator Award from the Oxygen Society in 1996; and held an American Heart Association Pre-doctoral Fellowship from the Illinois Affiliate from 1993 through 1995. His work on assessment of mitochondrial dysfunction, oxidative damage in aging has been increasingly recognized and appreciated by gerontologists worldwide.
We have published over 300 publications (most of them original research publications) with an overall h-index of 99. I have used animal models to discover biological pathways and genes that regulate the rate of aging and/or become causal to aging. Although aging is highly complex, my team has made significant advances in better understanding the biology of aging by understanding the cellular and molecular processes. As my team learns more about these biological processes, experiments can be designed to better understand when and how pathological changes begin with aging providing important clues toward developing the timing and type of interventions to prevent or treat disease. Five areas are covered on some of the discoveries and implications: (1) apoptosis and aging; (2) mitochondria and aging; (3) autophagy and aging; (4) iron and aging; and (5) preclinical and clinical studies to extend health span.
1) Apoptosis and Aging. We were the first to document the existence of apoptosis (programmed cell death) in muscle, brain and heart tissues with old age. For example, we showed a loss of myocytes in the aging heart due to Mt-mediated apoptosis. Our study was the first to report cytochrome c release from the mitochondria and alterations in Bcl-2 with age in vivo, providing a potential mechanism for the increase in apoptosis seen in the aging heart. Furthermore, we found similar mechanisms in muscle and brain tissues and were also the first to provide evidence that intervention such as caloric restriction (CR) and exercise can attenuate several mechanisms of apoptosis. (a) Phaneuf S, and Leeuwenburgh C, Cytochrome c release from mitochondria in the aging heart: a possible mechanism for apoptosis with age. Am J Physiol Regul Integr Comp Physiol. 2002; (b) Shelke RR, and Leeuwenburgh C, Lifelong CR increases expression of apoptosis repressor with a caspase recruitment domain (ARC) in the brain. FASEB J. 2003; (c) Dirks AJ, and Leeuwenburgh C, Aging and lifelong calorie restriction result in adaptations of skeletal muscle apoptosis repressor, apoptosis-inducing factor, X-linked inhibitor of apoptosis, caspase-3, and caspase-12. Free Radic Biol Med; and (d) Someya et al. Age-related hearing loss in C57BL/6J mice is mediated by Bak-dependent mitochondrial apoptosis Proc Natl Acad Sci USA. 2009.
2) Mitochondria and Aging. We found that Mt mutations drive mammalian aging and determined that Mt sirtuin-3 (Sirt3) is essential for maintaining Mt redox status. In 2005 we published a paper in Science (Kujoth, Science 2005) that reported our use of transgenic mice to show that for the first time that accumulating mtDNA mutations promotes apoptosis and is a central mechanism that drives mammalian aging. Our investigative teams showed that mice expressing a proofreading-deficient version of the Mt DNA polymerase g (POLG) accumulate mtDNA mutations while simultaneously displaying characteristics of accelerated aging. Accumulation of mtDNA mutations was also associated with the induction of apoptosis, particularly in tissues characterized by rapid cellular turnover. In addition, we published a paper in the journal Cell entitled, “Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss (AHL) under caloric restriction” (Someya, Cell 2010). This paper reported for the first time that the Mt sirtuin (Sirt3) had an important role in maintaining an important physiological function (hearing loss) with aging. It was already known from our previous studies that CR extends the lifespan and health span of a variety of species. What was unknown is whether Sirt3 slows the progression of AHL, a common age-related disorder. Several studies showed that that CR reduces oxidative DNA damage in multiple tissues and prevents AHL in wild-type mice but fails to modify these phenotypes in mice lacking the –mitochondrial- deacetylase Sirt3, a member of the sirtuin family. Collectively, these findings identify for the first time that Sirt3 plays an essential role in enhancing the Mt glutathione antioxidant defense system during CR and shows that Sirt3-dependent Mt adaptations are a central mechanism that slows aging in mammals. (a) Kujoth et al. Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science. 2005 (b) Someya et al. Sirt3 mediates reduction of oxidative damage and prevention of AHL under CR. Cell 2010 (c) Hiona et al. Mitochondrial DNA mutations induce mitochondrial dysfunction, apoptosis and sarcopenia in skeletal muscle of mitochondrial DNA mutator mice, PLOS One. 2010; and (d) Leeuwenburgh C and Prolla T. Genetics, redox signaling, oxidative stress, and apoptosis in mammalian aging. Antioxid Redox Signal. 2006.
3) Autophagy and Aging. We were the first to examine the molecular mechanisms of autophagy decline with aging (i.e., loss of LC3, LAMP-2, Atg4B, and Beclin-1 with and without transfection technology) and the ability of exercise or CR to stimulate autophagy. We found that LC3 gene and protein expression pattern as well as LAMP-2 gene expression, both downstream regulators of autophagy contributed to an age-related decline in autophagic degradation. Moreover, calorie restriction mediated beneficial effects by stimulating autophagy in the heart, indicating the potential for cardioprotective therapies. We documented that autophagy is limited in aged liver exposed to ischemia reperfusion injury. Loss of Atg4B in livers of old mice increases their sensitivity to I/R injury and therefore increasing autophagy might ameliorate liver damage and restore Mt function after I/R. Indeed, overexpression of either Atg4B or Beclin-1 recovered Atg4B, increased autophagy, blocked the onset of the Mt permeability transition, and suppressed cell death after I/R in old hepatocytes. We also extended these mechanistic finding to several human studies investigating PAD (ischemia/reperfusion highly prevalent), patients undergoing mechanical ventilation (inactivity of the diaphragm) during surgery, and in older obese subjects (inactivity causing the lack of autophagy). (a) Wohlgemuth SE, et al. Skeletal muscle autophagy and apoptosis during aging: effects of calorie restriction and lifelong exercise. Exp Gerontol. 2010; (b) Wohlgemuth et al. An exploratory analysis of the effects of a weight loss plus exercise program on cellular quality control mechanisms in older overweight women. Rejuvenation Res. 2011; (c) Wang JH et al. Autophagy suppresses age-dependent ischemia and reperfusion injury in livers of mice. Gastroenterology. 2011; and (d) Mankowski RT et al. Intraoperative hemidiaphragm electrical stimulation reduces oxidative stress and upregulates autophagy in surgery patients undergoing mechanical ventilation: exploratory study. J Transl Med. 2016.
4) Iron and Aging. In model systems of aging (mammals and C. elegans) we have unequivocally shown that cellular and Mt iron accumulate with age and alters Mt function. These finding provide a potential target for future interventions. In the Journal Aging Cell we showed in animals that an accumulation of Mt iron increased the susceptibility of Mt permeability transition pore opening, Mt dysfunction and oxidative damage, thereby enhancing the susceptibility to apoptosis. We also investigated iron accumulation in C. elegans (well-established model organism for aging research). Novel discoveries were made related to the Mt iron-sulfur cluster assembly protein ISCU-1/ISCU with age. We also investigated zinc transporter such as ZIP14 (slc39a14), which can also function as an iron transporters and their response-adaptations to pro-inflammatory stimuli, e.g., interleukin-6. More recently, we extended these mechanistic findings to further investigate muscle pathology (iron deregulation, Mt biology and muscle biology) in humans of different (low- vs. high-functioning) functional status. In humans, we showed marked disruption in several muscle iron-transport proteins such transferrin receptor-1 (TfR1), Zip14, mitoferrin, and frataxin. We very recently received an impact score of 13 and percentile of 1% on the NIH proposal, “Functional Decline in Low-Functioning Older Adults; Role of Iron Dysregulation.” This NIH grant is funded and has started (9/1/2022-6/30/2027; $2,978,789). This is a cross-sectional as well as a longitudinal study with 120 older participants to investigate for the first time systemic, cellular, and Mt metals (iron, copper, zinc) deregulation (transport, import, export) with aging. Again this testified my ability to translate animal studies to human clinical studies to help aid the discovery of potential biological targets and future interventions. (a) Seo AY et al. Mitochondrial iron accumulation with age and functional consequences. Aging Cell. 2008; (b) Sheng Y et al. A novel role of the mitochondrial iron-sulfur cluster assembly protein ISCU-1/ISCU in longevity and stress response. Geroscience. 2021; (c) Aydemir TB et al. Aging amplifies multiple phenotypic defects in mice with zinc transporter Zip14 (Slc39a14) deletion. Exp Gerontol. 2016; and (d) Picca A et al. Altered expression of mitoferrin and frataxin, larger labile iron pool and greater mitochondrial DNA damage in the skeletal muscle of older adults. Cells. 2020.
5) Preclinical and Clinical Studies to Extend Health Span. My most recent chapter (over the past 12 years) has focused on translating basic finding discoveries from the biology of aging and findings from preclinical intervention into human clinical trials to improve health span. In a team science approach with the University of Northwestern, University of Kentucky we are testing compounds (i.e., resveratrol, NAD+ precursors, epicatechins, curcumin, urolithin A, beet juice) and pharmacological agents (metformin, rapamycin, testosterone, telmisartan, losartan) that target genes such as sirtuins, AMPK, mTOR, PGC-1α and nitric oxide production. We have clinical studies ongoing or completed using compounds to target these master metabolic genes such as sirtuins (Sirt1 and Sirt3), mTOR, metabolic Mt biogenesis gene (PGC1a), AMPK, and compounds to increase the levels of intracellular NAD+ (which declines with age). Completed and ongoing clinical trials are:
• Resveratrol to Enhance Vitality and Vigor in Elders: The REVIVE Trial; • Nicotinamide riboside as an Enhancer of Exercise Therapy in hypertensive older adults: The NEET Trial; • Improve PAD PERformance with METformin: The PERMET Trial; • ENabling Reduction of low-Grade Inflammation in Seniors with losartan and omega-3 polyunsaturated fatty acids: The ENERGISE Trial; • Nicotinamide riboside and walking exercise intervention to reduce fatigue in older breast cancer survivors: Exercise and Nutritional Ergogenic to ReGain Energy: The ENERGE Study; and • NICotinamidE riboside with and without resveratrol to improve functioning in peripheral artery disease: The NICE Trial.
The most recent and largest clinical trial just funded by the NIH and initiated is Cocoa flavanols to improve walking performance in PAD: the COCOA-PAD III Trial. In the pilot study (completed R21) we showed a positive result in walking speed using cocoa (main active ingredient: epicatechin) and was published in Circulation Research. In that study we showed a therapeutic effect of cocoa on walking performance in people with PAD. This warranted the larger Phase III clinical trial to definitively determine whether cocoa significantly improves walking performance in people with PAD. (a) McDermott MM et al. Cocoa to Improve Walking Performance in Older People with Peripheral Artery Disease: The COCOA-PAD Pilot Randomized Clinical Trial. Circ Res. 2020; (b) Pahor M et al. Effect of Losartan and Fish Oil on Plasma IL-6 and Mobility in Older Persons. The ENRGISE Pilot Randomized Clinical Trial; J Gerontol A Biol Sci Med Sci. 2019. (c) McDermott MM et al. Effect of Low-Intensity vs. High-Intensity Home-Based Walking Exercise on Walk Distance in Patients with Peripheral Artery Disease: The LITE Randomized Clinical Trial. JAMA. 2021; and (d) McDermott MM et al. Effect of Resveratrol on Walking Performance in Older People with Peripheral Artery Disease: The RESTORE Randomized Clinical Trial. JAMA Cardiol. 2017.
B. Summary. My laboratory (since 1998 at UF; Biochemistry of Aging Laboratory) has been very productive translating basic and preclinical findings into clinical trials. I also work closely with the NIH Intervention Testing Program (ITP). The ITP is designed to test nutritional-pharmacological interventions to extend lifespan. Previously, we have been involved in intervention testing (i.e., rapamycin, aspirin, nordihydroguaiaretic acid, and glycine), and our recent ITP proposal C2021 on epicatechins (flavanol) was selected to start in 2022. I am very active in various Center grants. I am one of the principal investigators for the AHA’s Vascular Diseases SFRN. This project’s overall goal is to identify specific Mt defects associated with skeletal muscle pathophysiologic changes in elderly patients with vascular disease. The focus of another Center grant (a P50 and now an RM1) is to better understand the causes and consequences of sepsis in elderly surgery or trauma ICU patients. I am nationally and internationally recognized for my research and scholarship and also have multiple active national and international collaborations outside of UF.
Robert Mankowski Ph.D.
Dr. Robert Mankowski is an Assistant Professor at the Department of Aging and Geriatric Research. He obtained his PhD in Exercise Physiology at the Erasmus University Medical Center in Rotterdam, The Netherlands. His translational and team-science research is focused on preserving physical and cardiovascular function in older age. His research spans from investigating the effects of nutritional and exercise interventions on physical and cardiovascular function in moderately functioning older adults, to better understanding the epidemiology and pathobiology of poor long-term physical and cognitive outcomes in older survivors (including race and sex differences) of critical illness, especially sepsis. He aims to translate effective exercise (institution-based and remotely delivered) and nutritional interventions from moderately functioning older adults to poorly functioning older survivors of critical illness. His ultimate goal is to customize exercise and nutritional interventions in populations at risk of frailty, and thus improve quality of life and expand the health span.
Marco Pahor M.D.
MARCO PAHOR, M.D., is the director of the University of Florida Institute on Aging .
Pahor is an internationally recognized expert on population-based studies, clinical trials and multidisciplinary translational research in the fields of aging, disability and cardiovascular disease.
An experienced geriatrician and epidemiologist, Pahor has an excellent publication record, having authored or co-authored more than 450 papers in leading peer-reviewed journals, which have been cited by other researchers more than 5,0000 times. He has an extensive portfolio of grants from the National Institutes of Health and other agencies, and is a leader in research and education, serving as director of the Claude D. Pepper Older Americans Independence Center and of the faculty mentoring program of the UF Clinical and Translational Science Institute.
Before coming to UF in 2005, Pahor held a number of positions at Wake Forest University, including director of the Sticht Center on Aging, deputy associate dean of the office of research and head of the section on gerontology and geriatrics. His previous academic appointments were at the University of Tennessee, the National Institutes of Health, the University of Florence, Italy, and the Catholic University in Rome, where he also earned his medical degree and completed residency.
Pahor is on the Physical Exercise Task Force and the Aging Clinical Trials Advisory Panel of the National Institute on Aging. He has served as an editor for a number of academic journals, including Aging, Clinical and Experimental Research, the Journal of the American Geriatrics Society, the Journal of Gerontology: Medical Sciences and the Journal of Nutrition, Health and Aging. He has served on numerous NIH grant and program review panels.
Yi Sheng
I am working on the mechanism underlying aging with the C. elegans model, which can provide more knowledge for the aging of human beings.
Shinichi Someya Ph.D.
I am a tenured Associate Professor, Director of Online Graduate Program in Gerontology, and Co-Director of Physiology Concentration in Graduate Program in Biomedical Sciences in the Department of Physiology and Aging in the College of Medicine at the University of Florida. I received my BA from the University of California, Berkeley in 1991 and received my PhD from the University of Tokyo in 2005. I then pursued my postdoctoral training in the laboratory of Dr. Tomas Prolla in the Department of Genetics at the University of Wisconsin (2005-2011). I joined the faculty in the Department of Aging and Geriatric Research at the University of Florida as a tenure-track Assistant Professor in June of 2011 and was promoted to tenured Associate Professor in July of 2016.
I have a broad background in molecular cell biology, with specific training and expertise in auditory neuroscience, aging, mitochondrial biology, and hearing loss. Currently, my research focuses on sex differences in hearing, mitochondrial function, and cochlear aging. My work employs electrophysiology, histology, biochemistry, and molecular biology to assess auditory function and cochlear pathology. We use mice as a model system because the mouse inner ear is anatomically similar to that of human and the homologies between the mouse and human genomes are well-established.
At the University of Florida, I currently direct six graduate courses: GMS 6486 Biology of Aging (fall/spring/summer), SPA5102 Auditory Anatomy and Physiology (fall), SPA6581 Anatomy and Physiology of Balance (fall), SPA6581 Auditory Pharmacology (summer), and SPA6564 Communication and Aging (spring). I also teach 5 graduate courses as a lecturer, including GMS 6893 Clinical and Translational Science Institute Student Seminar (fall), GMS 6622 Mitochondrial Biology in Aging and Disease (fall), and GMS6070 Sensory Biology (spring). In my courses, I take a student-centered and interactive approach. I encourage students to participate actively.
The Someya Lab studies the molecular mechanisms that underlie sex differences in hearing, mitochondrial function, and aging. Our work employs molecular genetics tools to identify the genes and pathways involved in aging and mitochondrial dysfunction. These studies are complemented by the use of electrophysiology and histology to assess hearing function and cochlear pathology. We use mice as a model system because the mouse inner ear is anatomically similar to that of human and the homologies between the mouse and human genomes are well-established.
http://someyalab.aging.ufl.edu/about-someya-lab/
Stephanie Wohlgemuth Ph.D.
I have been trained and have worked as a comparative physiologist with a focus on metabolic and cellular responses to environmental stress, disease and aging in a variety of species, ranging from marine annelid worms and freshwater fishes to rodents, humans and large mammals. My research expertise spans from whole animal experiments to subcellular organelle isolation and functional assessment. Currently, I am focusing on mitochondrial biology in the context of aging. In the recently established Respirometry Lab in the Department of Physiology and Aging, I am providing consultations and various services with regard to mitochondrial assessments to the wider UF campus. My teaching experience includes undergraduate courses in general and developmental biology and graduate courses in muscle physiology, mitochondrial biology, and aging biology. I have worked in leadership positions in physiology laboratories for over 15 years, and have supervised, mentored and trained 50 undergraduate and graduate students, as well as technicians and postdoctoral scientists.