Christiaan Leeuwenburgh

Christiaan Leeuwenburgh, Ph.D.

Professor Department Of Physiology And Aging

Department: MD-AGING/ GERIATRIC RES-OTHER
Business Phone: (352) 273-5735
Business Email: cleeuwen@ufl.edu

About Christiaan Leeuwenburgh

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 oxidative stress and apoptosis with age in humans and rodent models. He is conducting research on the role of apoptosis 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 The Journal of Biological Chemistry, American Journal of Physiology and Science. He reviews regularly for numerous journals including American Journal of Physiology, Experimental Gerontology, Biogerontology, and the Journal of Gerontology and is a section editor for the Journal of Experimental Gerontology. 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 oxidative damage in aging and apoptosis has been increasingly recognized and appreciated by gerontologists worldwide.

Accomplishments

Professorship Award
2019 · University of Florida
Dr. G. Lombard Kelly Lecturer
2018 · Medical College of Georgia, Augusta University
Professorship Award
2017 · University of Florida
University of Florida Research Foundation Professor
2011-2013 · University of Florida
Exemplary Teacher Award
2010 · College of Medicine, University of Florida
University of Florida Research Foundation Professor
2004-2006 · University of Florida
Nathan W. Shock Lecture Award
2004 · National Institute on Aging
American Heart Association, Young Investigator Award
2000-2002 · American Heart Association
Merck Geriatric Cardiology Research Award
1999-2000 · Society of Geriatric Cardiology
National Research Service Award, NRSA-NIH
1997-1998 · National Institute of Aging
Young Investigator Award, Oxygen Society, Intern
1996 · Soc. Free Rad. Res., Miami, FL
Honorary Fellow
1994-1995 · University of Wisconsin, Madison, WI
American Heart Association, Pre-doctoral Fellowship
1993-1995 · American Heart Association, Illinois Affiliate
The Avery Brundage Scholarship Award
1993 · University of Illinois, Urbana-Champaign, IL

Teaching Profile

Courses Taught
2010,2013-2016,2016-2021,2018-2021,2020-2021
GMS6622 Mitochondrial Biology in Aging and Disease
2018
GMS7980 Research for Doctoral Dissertation
2018
GMS7979 Advanced Research
2018
VME7980 Research for Doctoral Dissertation
2014,2016-2018
GMS6421 Cell Biology
2013-2015
GMS6417 Integrative Aging Physiology
2015
GMS6063 Mechanisms of Aging
2021-2022
PAS5020 Intro to Medicine 2
Teaching Philosophy
Educational Program 1) My educational approach has always been to explain complex topics in simpler terms to disseminate the information and science to students and ESIs effectively. I believe that very solid knowledge about the materials is critical, and enthusiasm when presenting is very important to stimulate engagement. Also, the focus of my teaching has always been on providing specific examples within the topic content and frequently engaging the students with pertinent questions. To achieve this, I have used a competency-based training approach that posits that learning emerges from experiences that generate assumptions through which we interpret our experience. Notably, novel experiences and questions stimulate reflection and perspective challenging, thereby promoting new interpretations and conceptualizations, or transformative learning. I have capitalized on this cycle by creating tailored teaching and training programs for many students and ESIs. With ESIs (see section C. Other Instructional Activities), the emphasis is on the concept of team science, and team-based learning serves as the primary teaching method. 2) In many of my education programs I emphasize interdisciplinary approaches that teach the combined knowledge of basic, translational, social, behavioral, epidemiological, and clinical research. I am very passionate about teaching and exchanging ideas, especially for future investigation and research. I strongly believe that learner relevance related to scientific topics can also be very valuable for seeing the connection between the content and potential improvements in the learner’s own daily life, specifically related to health and human function. Broadly my goal is to inform students and trainees on how knowledge of the biology on aging might influence their scientific directions which could influence health span interventions and their own personal health.

Research Profile

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 will be 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. We tested 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. Specifically, we have clinical studies ongoing or completed using compounds to target 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.

Open Researcher and Contributor ID (ORCID)

0000-0003-0826-4257

Publications

2022
Analysis of Biological Aging and Risks of All-Cause and Cardiovascular Disease-Specific Death in Cancer Survivors.
JAMA network open. 5(6) [DOI] 10.1001/jamanetworkopen.2022.18183. [PMID] 35731518.
2022
Dysregulated Genes, MicroRNAs, Biological Pathways, and Gastrocnemius Muscle Fiber Types Associated With Progression of Peripheral Artery Disease: A Preliminary Analysis
Journal of the American Heart Association. 11(21) [DOI] 10.1161/jaha.121.023085.
2022
Effects of Walking Exercise at a Pace With Versus Without Ischemic Leg Symptoms on Functional Performance Measures in People With Lower Extremity Peripheral Artery Disease: The LITE Randomized Clinical Trial
Journal of the American Heart Association. 11(15) [DOI] 10.1161/jaha.121.025063.
2022
Frailty and risk of mortality in older cancer survivors and adults without a cancer history: Evidence from the National Health and Nutrition Examination Survey, 1999-2014.
Cancer. 128(15):2978-2987 [DOI] 10.1002/cncr.34258. [PMID] 35608563.
2022
Mitochondrial-derived vesicles in skeletal muscle remodeling and adaptation.
Seminars in cell & developmental biology. [DOI] 10.1016/j.semcdb.2022.03.023. [PMID] 35367122.
2022
Older Adults Demonstrate Biomarker Evidence of the Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) After Sepsis.
The journals of gerontology. Series A, Biological sciences and medical sciences. 77(1):188-196 [DOI] 10.1093/gerona/glab080. [PMID] 33721883.
2022
Post-meeting report of the 2022 On-site Padua Days on Muscle and Mobility Medicine, March 30 – April 3, 2022, Padua, Italy.
European journal of translational myology. 32(2) [DOI] 10.4081/ejtm.2022.10521. [PMID] 35421919.
2022
Sex differences associate with late microbiome alterations after murine surgical sepsis.
The journal of trauma and acute care surgery. 93(2):137-146 [DOI] 10.1097/TA.0000000000003599. [PMID] 35324554.
2022
Time-Restricted Eating Regimen Differentially Affects Circulatory miRNA Expression in Older Overweight Adults
Nutrients. 14(9) [DOI] 10.3390/nu14091843. [PMID] 35565812.
2021
A hypolipoprotein sepsis phenotype indicates reduced lipoprotein antioxidant capacity, increased endothelial dysfunction and organ failure, and worse clinical outcomes.
Critical care (London, England). 25(1) [DOI] 10.1186/s13054-021-03757-5. [PMID] 34535154.
2021
A novel role of the mitochondrial iron-sulfur cluster assembly protein ISCU-1/ISCU in longevity and stress response.
GeroScience. 43(2):691-707 [DOI] 10.1007/s11357-021-00327-z. [PMID] 33527323.
2021
Assessing the feasibility of using the short physical performance battery to measure function in the immediate postoperative period after total knee replacement.
European journal of translational myology. 31(2) [DOI] 10.4081/ejtm.2021.9673. [PMID] 33840178.
2021
Blood flow restriction exercise to attenuate postoperative loss of function after total knee replacement: a randomized pilot study.
European journal of translational myology. 31(3) [DOI] 10.4081/ejtm.2021.9932. [PMID] 34459574.
2021
Chronic Critical Illness Elicits a Unique Circulating Leukocyte Transcriptome in Sepsis Survivors.
Journal of clinical medicine. 10(15) [DOI] 10.3390/jcm10153211. [PMID] 34361995.
2021
Clinical characteristics and response to supervised exercise therapy of people with lower extremity peripheral artery disease.
Journal of vascular surgery. 73(2):608-625 [DOI] 10.1016/j.jvs.2020.04.498. [PMID] 32416309.
2021
Comparative toxicities of BPA, BPS, BPF, and TMBPF in the nematode Caenorhabditis elegans and mammalian fibroblast cells.
Toxicology. 461 [DOI] 10.1016/j.tox.2021.152924. [PMID] 34474090.
2021
Critical Roles of Calpastatin in Ischemia/Reperfusion Injury in Aged Livers.
Cells. 10(8) [DOI] 10.3390/cells10081863. [PMID] 34440632.
2021
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. 325(13):1266-1276 [DOI] 10.1001/jama.2021.2536. [PMID] 33821898.
2021
Inflammation in Relation to Sarcopenia and Sarcopenic Obesity among Older Adults Living with Chronic Comorbidities: Results from the National Health and Nutrition Examination Survey 1999-2006.
Nutrients. 13(11) [DOI] 10.3390/nu13113957. [PMID] 34836213.
2021
Iron homeostasis and organismal aging.
Ageing research reviews. 72 [DOI] 10.1016/j.arr.2021.101510. [PMID] 34767974.
2021
Lipid and Lipoprotein Dysregulation in Sepsis: Clinical and Mechanistic Insights into Chronic Critical Illness.
Journal of clinical medicine. 10(8) [DOI] 10.3390/jcm10081693. [PMID] 33920038.
2021
Lipid and lipoprotein predictors of functional outcomes and long-term mortality after surgical sepsis.
Annals of intensive care. 11(1) [DOI] 10.1186/s13613-021-00865-x. [PMID] 34018068.
2021
Meaningful change in 6-minute walk in people with peripheral artery disease.
Journal of vascular surgery. 73(1):267-276.e1 [DOI] 10.1016/j.jvs.2020.03.052. [PMID] 32335305.
2021
Resveratrol and exercise combined to treat functional limitations in late life: A pilot randomized controlled trial.
Experimental gerontology. 143 [DOI] 10.1016/j.exger.2020.111111. [PMID] 33068691.
2021
Septic Stability? Gut Microbiota in Young Adult Mice Maintains Overall Stability After Sepsis Compared to Old Adult Mice.
Shock (Augusta, Ga.). 55(4):519-525 [DOI] 10.1097/SHK.0000000000001648. [PMID] 32826817.
2021
Sustained physical activity in peripheral artery disease: Associations with disease severity, functional performance, health-related quality of life, and subsequent serious adverse events in the LITE randomized clinical trial.
Vascular medicine (London, England). 26(5):497-506 [DOI] 10.1177/1358863X21989430. [PMID] 33829920.
2021
The Age-Sensitive Efficacy of Calorie Restriction on Mitochondrial Biogenesis and mtDNA Damage in Rat Liver.
International journal of molecular sciences. 22(4) [DOI] 10.3390/ijms22041665. [PMID] 33562258.
2021
The Effect of Aging Physiology on Critical Care.
Critical care clinics. 37(1):135-150 [DOI] 10.1016/j.ccc.2020.08.006. [PMID] 33190766.
2021
The impact of sarcopenia and acute muscle mass loss on long-term outcomes in critically ill patients with intra-abdominal sepsis.
Journal of cachexia, sarcopenia and muscle. 12(5):1203-1213 [DOI] 10.1002/jcsm.12752. [PMID] 34196134.
2021
Transcriptomic responses from improved murine sepsis models can better mimic human surgical sepsis.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 35(2) [DOI] 10.1096/fj.202002150R. [PMID] 33140449.
2021
Vascular dysfunction as a potential culprit of sarcopenia.
Experimental gerontology. 145 [DOI] 10.1016/j.exger.2020.111220. [PMID] 33373710.
2021
Walking Exercise Therapy Effects on Lower Extremity Skeletal Muscle in Peripheral Artery Disease.
Circulation research. 128(12):1851-1867 [DOI] 10.1161/CIRCRESAHA.121.318242. [PMID] 34110902.
2020
Altered Expression of Mitoferrin and Frataxin, Larger Labile Iron Pool and Greater Mitochondrial DNA Damage in the Skeletal Muscle of Older Adults.
Cells. 9(12) [DOI] 10.3390/cells9122579. [PMID] 33276460.
2020
American Heart Association Vascular Disease Strategically Focused Research Network.
Arteriosclerosis, thrombosis, and vascular biology. 40(3):e47-e54 [DOI] 10.1161/ATVBAHA.120.313967. [PMID] 31969016.
2020
Associations of Peripheral Artery Disease With Calf Skeletal Muscle Mitochondrial DNA Heteroplasmy.
Journal of the American Heart Association. 9(7) [DOI] 10.1161/JAHA.119.015197. [PMID] 32200714.
2020
Associations of Poly (ADP-Ribose) Polymerase1 abundance in calf skeletal muscle with walking performance in peripheral artery disease.
Experimental gerontology. 140 [DOI] 10.1016/j.exger.2020.111048. [PMID] 32755612.
2020
Cocoa to Improve Walking Performance in Older People With Peripheral Artery Disease: The COCOA-PAD Pilot Randomized Clinical Trial.
Circulation research. 126(5):589-599 [DOI] 10.1161/CIRCRESAHA.119.315600. [PMID] 32078436.
2020
Comparing 6-minute walk versus treadmill walking distance as outcomes in randomized trials of peripheral artery disease.
Journal of vascular surgery. 71(3):988-1001 [DOI] 10.1016/j.jvs.2019.05.058. [PMID] 31870756.
2020
Correlations of Calf Muscle Macrophage Content With Muscle Properties and Walking Performance in Peripheral Artery Disease.
Journal of the American Heart Association. 9(10) [DOI] 10.1161/JAHA.118.015929. [PMID] 32390569.
2020
Differential response to targeted acupuncture by gender in patients with gastrointestinal cancer cachexia: secondary analysis of a randomized controlled trial.
Acupuncture in medicine : journal of the British Medical Acupuncture Society. 38(1):53-60 [DOI] 10.1177/0964528419873670. [PMID] 31544469.
2020
Innovations in Geroscience to enhance mobility in older adults.
Experimental gerontology. 142 [DOI] 10.1016/j.exger.2020.111123. [PMID] 33191210.
2020
Lipid intensive drug therapy for sepsis pilot: A Bayesian phase I clinical trial.
Journal of the American College of Emergency Physicians open. 1(6):1332-1340 [DOI] 10.1002/emp2.12237. [PMID] 33392541.
2020
Mitochondrial DNA damage in calf skeletal muscle and walking performance in people with peripheral artery disease.
Free radical biology & medicine. 160:680-689 [DOI] 10.1016/j.freeradbiomed.2020.09.004. [PMID] 32911084.
2020
Nicotinamide riboside-A missing piece in the puzzle of exercise therapy for older adults?
Experimental gerontology. 137 [DOI] 10.1016/j.exger.2020.110972. [PMID] 32450270.
2020
Older Sepsis Survivors Suffer Persistent Disability Burden and Poor Long-Term Survival.
Journal of the American Geriatrics Society. 68(9):1962-1969 [DOI] 10.1111/jgs.16435. [PMID] 32294254.
2020
Skeletal Muscle Pathology in Peripheral Artery Disease: A Brief Review.
Arteriosclerosis, thrombosis, and vascular biology. 40(11):2577-2585 [DOI] 10.1161/ATVBAHA.120.313831. [PMID] 32938218.
2020
The COVID-19 pandemic and physical activity.
Sports medicine and health science. 2(2):55-64 [DOI] 10.1016/j.smhs.2020.05.006. [PMID] 34189484.
2019
Advanced Age Is Associated with Iron Dyshomeostasis and Mitochondrial DNA Damage in Human Skeletal Muscle
. 8(12)
2019
Advanced Age Is Associated with Iron Dyshomeostasis and Mitochondrial DNA Damage in Human Skeletal Muscle.
Cells. 8(12) [DOI] 10.3390/cells8121525. [PMID] 31783583.
2019
Associations of Weight Change With Changes in Calf Muscle Characteristics and Functional Decline in Peripheral Artery Disease.
Journal of the American Heart Association. 8(13) [DOI] 10.1161/JAHA.118.010890. [PMID] 31257970.
2019
Differences in Liver TFAM Binding to mtDNA and mtDNA Damage between Aged and Extremely Aged Rats.
International journal of molecular sciences. 20(10) [DOI] 10.3390/ijms20102601. [PMID] 31137890.
2019
Differential response to targeted acupuncture by gender in patients with gastrointestinal cancer cachexia: secondary analysis of a randomized controlled trial.
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2019
Effect of Losartan and Fish Oil on Plasma IL-6 and Mobility in Older Persons. The ENRGISE Pilot Randomized Clinical Trial.
The journals of gerontology. Series A, Biological sciences and medical sciences. 74(10):1612-1619 [DOI] 10.1093/gerona/gly277. [PMID] 30541065.
2019
Glycine supplementation extends lifespan of male and female mice.
Aging cell. 18(3) [DOI] 10.1111/acel.12953. [PMID] 30916479.
2019
Higher dose of resveratrol elevated cardiovascular disease risk biomarker levels in overweight older adults – A pilot study
Experimental Gerontology. 131 [DOI] 10.1016/j.exger.2019.110821. [PMID] 31891746.
2019
LIPid Intensive Drug therapy for Sepsis Pilot (LIPIDS-P): Phase I/II clinical trial protocol of lipid emulsion therapy for stabilising cholesterol levels in sepsis and septic shock.
BMJ open. 9(9) [DOI] 10.1136/bmjopen-2019-029348. [PMID] 31537565.
2019
Myeloid-derived suppressor cell function and epigenetic expression evolves over time after surgical sepsis.
Critical care (London, England). 23(1) [DOI] 10.1186/s13054-019-2628-x. [PMID] 31722736.
2019
Old Mice Demonstrate Organ Dysfunction as well as Prolonged Inflammation, Immunosuppression, and Weight Loss in a Modified Surgical Sepsis Model.
Critical care medicine. 47(11):e919-e929 [DOI] 10.1097/CCM.0000000000003926. [PMID] 31389840.
2019
Persistent inflammation and anemia among critically ill septic patients.
The journal of trauma and acute care surgery. 86(2):260-267 [DOI] 10.1097/TA.0000000000002147. [PMID] 30489504.
2019
Prognostic value of NT-proBNP levels in the acute phase of sepsis on lower long-term physical function and muscle strength in sepsis survivors.
Critical care (London, England). 23(1) [DOI] 10.1186/s13054-019-2505-7. [PMID] 31234943.
2019
Targeting mitochondrial quality control for treating sarcopenia: lessons from physical exercise.
Expert opinion on therapeutic targets. 23(2):153-160 [DOI] 10.1080/14728222.2019.1559827. [PMID] 30580640.
2019
The Effects of Time Restricted Feeding on Overweight, Older Adults: A Pilot Study.
Nutrients. 11(7) [DOI] 10.3390/nu11071500. [PMID] 31262054.
2018
Administration of Enalapril Started Late in Life Attenuates Hypertrophy and Oxidative Stress Burden, Increases Mitochondrial Mass, and Modulates Mitochondrial Quality Control Signaling in the Rat Heart.
Biomolecules. 8(4) [DOI] 10.3390/biom8040177. [PMID] 30563025.
2018
Benchmarking clinical outcomes and the immunocatabolic phenotype of chronic critical illness after sepsis in surgical intensive care unit patients.
The journal of trauma and acute care surgery. 84(2):342-349 [DOI] 10.1097/TA.0000000000001758. [PMID] 29251709.
2018
Circulating Mitochondrial DNA at the Crossroads of Mitochondrial Dysfunction and Inflammation During Aging and Muscle Wasting Disorders.
Rejuvenation research. 21(4):350-359 [DOI] 10.1089/rej.2017.1989. [PMID] 29125070.
2018
Effects of Fermented Papaya Preparation (Fpp) on Safety Outcomes in Older Adults – a Short Report of a Placebo- Controlled Clinical Trial
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2018
Exciting Perspectives for Translational Myology in the Abstracts of the 2018Spring Paduamuscledays: Giovanni Salviati Memorial – Chapter II – Abstracts of March 15, 2018
European Journal of Translational Myology. 28(1):10-29 [DOI] 10.4081/ejtm.2018.7364. [PMID] 30057726.
2018
Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting.
Obesity (Silver Spring, Md.). 26(2):254-268 [DOI] 10.1002/oby.22065. [PMID] 29086496.
2018
HDL Cholesterol Efflux is Impaired in Older Patients with Early Sepsis: A Subanalysis of a Prospective Pilot Study.
Shock (Augusta, Ga.). 50(1):66-70 [DOI] 10.1097/SHK.0000000000001030. [PMID] 29049133.
2018
HDL inflammatory index correlates with and predicts severity of organ failure in patients with sepsis and septic shock.
PloS one. 13(9) [DOI] 10.1371/journal.pone.0203813. [PMID] 30216360.
2018
Increased TFAM binding to mtDNA damage hot spots is associated with mtDNA loss in aged rat heart.
Free radical biology & medicine. 124:447-453 [DOI] 10.1016/j.freeradbiomed.2018.06.041. [PMID] 29969715.
2018
Loss of sirtuin 1 and mitofusin 2 contributes to enhanced ischemia/reperfusion injury in aged livers.
Aging cell. 17(4) [DOI] 10.1111/acel.12761. [PMID] 29774638.
2018
Mitochondrial quality control mechanisms as molecular targets in cardiac ageing.
Nature reviews. Cardiology. 15(9):543-554 [DOI] 10.1038/s41569-018-0059-z. [PMID] 30042431.
2018
Peripheral artery disease, calf skeletal muscle mitochondrial DNA copy number, and functional performance.
Vascular medicine (London, England). 23(4):340-348 [DOI] 10.1177/1358863X18765667. [PMID] 29734865.
2018
Persistent inflammation, immunosuppression, and catabolism and the development of chronic critical illness after surgery.
Surgery. 164(2):178-184 [DOI] 10.1016/j.surg.2018.04.011. [PMID] 29807651.
2018
Persistent injury-associated anemia and aging: Novel insights
Journal of Trauma and Acute Care Surgery. 84(3):490-496
2018
Persistent injury-associated anemia and aging: Novel insights.
The journal of trauma and acute care surgery. 84(3):490-496 [DOI] 10.1097/TA.0000000000001766. [PMID] 29466280.
2018
Persistent injury-associated anemia in aged rats.
Experimental gerontology. 103:63-68 [DOI] 10.1016/j.exger.2018.01.001. [PMID] 29307734.
2018
The “BIOmarkers associated with Sarcopenia and PHysical frailty in EldeRly pErsons” (BIOSPHERE) study: Rationale, design and methods.
European journal of internal medicine. 56:19-25 [DOI] 10.1016/j.ejim.2018.05.001. [PMID] 29753582.
2017
Device-Measured Physical Activity As a Predictor of Disability in Mobility-Limited Older Adults.
Journal of the American Geriatrics Society. 65(10):2251-2256 [DOI] 10.1111/jgs.15037. [PMID] 28799216.
2017
Effect of Resveratrol on Walking Performance in Older People With Peripheral Artery Disease: The RESTORE Randomized Clinical Trial.
JAMA cardiology. 2(8):902-907 [DOI] 10.1001/jamacardio.2017.0538. [PMID] 28403379.
2017
Effects of Popular Diets without Specific Calorie Targets on Weight Loss Outcomes: Systematic Review of Findings from Clinical Trials.
Nutrients. 9(8) [DOI] 10.3390/nu9080822. [PMID] 28758964.
2017
ENabling Reduction of Low-grade Inflammation in SEniors Pilot Study: Concept, Rationale, and Design.
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2017
Erratum to: Walking performance is positively correlated to calf muscle fiber size in peripheral artery disease subjects, but fibers show aberrant mitophagy: an observational study
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Journal of translational medicine. 15(1) [DOI] 10.1186/s12967-017-1127-6. [PMID] 28241774.
2017
Exercise-Induced Autophagy in Fatty Liver Disease.
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Exploring the Predictive Ability of Dysfunctional High-Density Lipoprotein for Adverse Outcomes in Emergency Department Patients with Sepsis: A Preliminary Investigation.
Shock (Augusta, Ga.). 48(5):539-544 [DOI] 10.1097/SHK.0000000000000887. [PMID] 28452909.
2017
Fueling Inflamm-Aging through Mitochondrial Dysfunction: Mechanisms and Molecular Targets.
International journal of molecular sciences. 18(5) [DOI] 10.3390/ijms18050933. [PMID] 28452964.
2017
Impact of chemotherapy on medium-term physical function and activity of older breast cancer survivors, and associated biomarkers.
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2017
Resveratrol and exercise to treat functional limitations in late life: design of a randomized controlled trial.
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2017
Sepsis and Critical Illness Research Center investigators: protocols and standard operating procedures for a prospective cohort study of sepsis in critically ill surgical patients.
BMJ open. 7(7) [DOI] 10.1136/bmjopen-2016-015136. [PMID] 28765125.
2017
Systemic inflammation, body composition, and physical performance in old community-dwellers.
Journal of cachexia, sarcopenia and muscle. 8(1):69-77 [DOI] 10.1002/jcsm.12134. [PMID] 27897412.
2016
“What makes some rats live so long?” The mitochondrial contribution to longevity through balance of mitochondrial dynamics and mtDNA content.
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2016
Aging amplifies multiple phenotypic defects in mice with zinc transporter Zip14 (Slc39a14) deletion.
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2016
Autophagy in the liver: cell’s cannibalism and beyond.
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2016
Beneficial effects of exercise on age-related mitochondrial dysfunction and oxidative stress in skeletal muscle.
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Effects of Long-Term Exercise on Age-Related Hearing Loss in Mice
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2016
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
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2016
Integrated control of brown adipose tissue
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2016
Intraoperative hemidiaphragm electrical stimulation reduces oxidative stress and upregulates autophagy in surgery patients undergoing mechanical ventilation: exploratory study.
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2016
Low- Versus High-Intensity Plyometric Exercise During Rehabilitation After Anterior Cruciate Ligament Reconstruction
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Low- Versus High-Intensity Plyometric Exercise During Rehabilitation After Anterior Cruciate Ligament Reconstruction.
The American journal of sports medicine. 44(3):609-17 [DOI] 10.1177/0363546515620583. [PMID] 26797700.
2016
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Journal of translational medicine. 14(1) [DOI] 10.1186/s12967-016-1030-6. [PMID] 27687713.
2015
A Detailed Characterization of the Dysfunctional Immunity and Abnormal Myelopoiesis Induced by Severe Shock and Trauma in the Aged.
Journal of immunology (Baltimore, Md. : 1950). 195(5):2396-407 [DOI] 10.4049/jimmunol.1500984. [PMID] 26246141.
2015
Advanced age is associated with worsened outcomes and a unique genomic response in severely injured patients with hemorrhagic shock.
Critical care (London, England). 19(1) [DOI] 10.1186/s13054-015-0788-x. [PMID] 25880307.
2015
Age-related cellular changes in the long-lived bivalve A. islandica.
Age (Dordrecht, Netherlands). 37(5) [DOI] 10.1007/s11357-015-9831-8. [PMID] 26318854.
2015
Calorie Restriction Combined With Resveratrol Induces Autophagy and Protects 26-Month-Old Rat Hearts From Doxorubicin-Induced Toxicity (Vol 74, Pg 252, 2014)
Free Radical Biology and Medicine. 81 [DOI] 10.1016/j.freeradbiomed.2014.09.019.
2015
Dietary Antioxidants as Modifiers of Physiologic Adaptations to Exercise.
Medicine and science in sports and exercise. 47(9):1857-68 [DOI] 10.1249/MSS.0000000000000620. [PMID] 25606815.
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Effect of Resistance Training During the Month of Ramadan on Antioxidants and Oxidative Stress Biomarkers in Recreational Bodybuilders
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Human Myeloid Derived Suppressor Cells Induce Immune Suppression After Severe Sepsis
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Increased inflammation but similar physical composition and function in older-aged, HIV-1 infected subjects.
BMC immunology. 16 [DOI] 10.1186/s12865-015-0106-z. [PMID] 26204934.
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Practicality of intermittent fasting in humans and its effect on oxidative stress and genes related to aging and metabolism.
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Successful aging: Advancing the science of physical independence in older adults.
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2015
The Role of Genome Instability in Frailty: Mitochondria versus Nucleus
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The Role of Genome Instability in Frailty: Mitochondria versus Nucleus.
Nestle Nutrition Institute workshop series. 83:19-27 [DOI] 10.1159/000382055. [PMID] 26524430.
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A better understanding of why murine models of trauma do not recapitulate the human syndrome.
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2014
A comparison among the tissue-specific effects of aging and calorie restriction on TFAM amount and TFAM-binding activity to mtDNA in rat.
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2014
Active muscle regeneration following eccentric contraction-induced injury is similar between healthy young and older adults.
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2014
Advanced Age Is An Independent Predictor of Complicated Outcomes and Mortality Among Severely Injured Pateints in Hemorrhagic Shock
Shock. 41(2)
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Aged mice are unable to mount an effective myeloid response to sepsis.
Journal of immunology (Baltimore, Md. : 1950). 192(2):612-22 [DOI] 10.4049/jimmunol.1302109. [PMID] 24337739.
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Brown adipose tissue and the cold war against obesity.
Diabetes. 63(12):3998-4000 [DOI] 10.2337/db14-1373. [PMID] 25414014.
2014
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Free radical biology & medicine. 74:252-62 [DOI] 10.1016/j.freeradbiomed.2014.06.011. [PMID] 24975655.
2014
Effect of intermittent phrenic nerve stimulation during cardiothoracic surgery on mitochondrial respiration in the human diaphragm.
Critical care medicine. 42(2):e152-6 [DOI] 10.1097/CCM.0b013e3182a63fdf. [PMID] 24126442.
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Genomic Analysis of Individual Leukocyte Populations After Severe Trauma
Shock. 41(2)
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Host responses to sepsis vary in different low-lethality murine models.
PloS one. 9(5) [DOI] 10.1371/journal.pone.0094404. [PMID] 24788351.
2014
Inadequate Pmn Chemokine Receptor Expression After Polymicrobial Abdominal Sepsis Contributes To Defective Pmn Chemotaxis in the Aged
Shock. 41(2)
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Patterns of circulating inflammatory biomarkers in older persons with varying levels of physical performance: a partial least squares-discriminant analysis approach.
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2014
Persistent inflammation, immunosuppression, and catabolism syndrome after severe blunt trauma.
The journal of trauma and acute care surgery. 76(1):21-9; discussion 29 [DOI] 10.1097/TA.0b013e3182ab1ab5. [PMID] 24368353.
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Phrenic nerve stimulation increases human diaphragm fiber force after cardiothoracic surgery.
American journal of respiratory and critical care medicine. 190(7):837-9 [DOI] 10.1164/rccm.201405-0993LE. [PMID] 25271750.
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Protective immunity and defects in the neonatal and elderly immune response to sepsis.
Journal of immunology (Baltimore, Md. : 1950). 192(7):3156-65 [DOI] 10.4049/jimmunol.1301726. [PMID] 24591376.
2014
Quantitation of Oxidative Stress and Base Excision Repair in Skeletal Muscle of High- and Low-Functioning Elderly Individuals
The FASEB's Journal. 28(1, S)
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Safety and metabolic outcomes of resveratrol supplementation in older adults: results of a twelve-week, placebo-controlled pilot study.
Experimental gerontology. 57:181-7 [DOI] 10.1016/j.exger.2014.05.015. [PMID] 24866496.
2014
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Critical care medicine. 42(9) [DOI] 10.1097/CCM.0000000000000482. [PMID] 25126819.
2013
Age- and calorie restriction-related changes in rat brain mitochondrial DNA and TFAM binding.
Age (Dordrecht, Netherlands). 35(5):1607-20 [DOI] 10.1007/s11357-012-9465-z. [PMID] 22945739.
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Aging and calorie restriction oppositely affect mitochondrial biogenesis through TFAM binding at both origins of mitochondrial DNA replication in rat liver.
PloS one. 8(9) [DOI] 10.1371/journal.pone.0074644. [PMID] 24058615.
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Autophagy and leucine promote chronological longevity and respiration proficiency during calorie restriction in yeast.
Experimental gerontology. 48(10):1107-19 [DOI] 10.1016/j.exger.2013.01.006. [PMID] 23337777.
2013
Caloric Restriction and Resveratrol Attenuate Doxorubicin-Induced Vascular Dysfunction in Old Rat Mesenteric Arteries
The FASEB's Journal. 27
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Caloric Restriction to Moderate Senescence: Mechanisms and Clinical Utility
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Caloric Restriction to Moderate Senescence: Mechanisms and Clinical Utility.
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Current nutritional recommendations and novel dietary strategies to manage sarcopenia.
The Journal of frailty & aging. 2(1):38-53 [PMID] 26082911.
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Dysregulation of mitochondrial quality control processes contribute to sarcopenia in a mouse model of premature aging.
PloS one. 8(7) [DOI] 10.1371/journal.pone.0069327. [PMID] 23935986.
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Fasting or caloric restriction for healthy aging.
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Mitochondrial dysfunction and sarcopenia of aging: from signaling pathways to clinical trials.
The international journal of biochemistry & cell biology. 45(10):2288-301 [DOI] 10.1016/j.biocel.2013.06.024. [PMID] 23845738.
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Mitochondrial Function and Fatigability in Older Adults Who Report Severe Fatigue
Gerontologist. 53(1)
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Mitochondrial pathways in sarcopenia of aging and disuse muscle atrophy.
Biological chemistry. 394(3):393-414 [DOI] 10.1515/hsz-2012-0247. [PMID] 23154422.
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Oxidative damage increases with reproductive energy expenditure and is reduced by food-supplementation.
Evolution; international journal of organic evolution. 67(5):1527-36 [DOI] 10.1111/evo.12014. [PMID] 23617928.
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Role of mitochondrial dysfunction and altered autophagy in cardiovascular aging and disease: from mechanisms to therapeutics.
American journal of physiology. Heart and circulatory physiology. 305(4):H459-76 [DOI] 10.1152/ajpheart.00936.2012. [PMID] 23748424.
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Short-term caloric restriction, resveratrol, or combined treatment regimens initiated in late-life alter mitochondrial protein expression profiles in a fiber-type specific manner in aged animals.
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Skeletal Muscle Energy Output Among Older Adults Could Rely On Electrons Flux Through the Mitochondrial Inner Membrane
Fundamental & Clinical Pharmacology. 27
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Skeletal muscle mitochondrial energetics are associated with maximal aerobic capacity and walking speed in older adults.
The journals of gerontology. Series A, Biological sciences and medical sciences. 68(4):447-55 [DOI] 10.1093/gerona/gls196. [PMID] 23051977.
2013
The effect of fasting on indicators of muscle damage.
Experimental gerontology. 48(10):1101-6 [DOI] 10.1016/j.exger.2012.12.006. [PMID] 23266375.
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Upregulated autophagy protects cardiomyocytes from oxidative stress-induced toxicity.
Autophagy. 9(3):328-44 [DOI] 10.4161/auto.22971. [PMID] 23298947.
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Urinary Concentrations of Type II Collagen Cleavage Following Anterior Cruciate Ligament Reconstruction
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2012
Age-related differences in lower extremity tissue compartments and associations with physical function in older adults.
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Altered Levels of Mitochondrial Morphology Proteins in Skeletal Muscle of Mitochondrial Dna Mutator Mice
The FASEB's Journal. 26
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Amino acid homeostasis and chronological longevity in Saccharomyces cerevisiae
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Apoptosis in skeletal myocytes: a potential target for interventions against sarcopenia and physical frailty – a mini-review.
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Chronic pain, perceived stress, and cellular aging: an exploratory study.
Molecular pain. 8 [DOI] 10.1186/1744-8069-8-12. [PMID] 22325162.
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Contribution of impaired mitochondrial autophagy to cardiac aging: mechanisms and therapeutic opportunities
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Contribution of impaired mitochondrial autophagy to cardiac aging: mechanisms and therapeutic opportunities.
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Critical role of autophage in ischemia/reperfusion injury to aged livers
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Effect of Resveratrol and Caloric Restriction On Mitochondrial Regulation and Apoptotic Susceptibility in Aged Rat Skeletal Muscle
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Guidelines for the use and interpretation of assays for monitoring autophagy.
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Impaired iron status in aging research.
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Lifelong Wheel Running With Mild Caloric Restriction Protects Against the Age-Related Disruption of the Dystrophin-Glycoprotein Complex (Dgc) in Skeletal Muscle
The FASEB's Journal. 26
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Mitochondrial Transcription Factor a Binding To Mitochondrial Dna During Aging and Calorie Restriction
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Redox balance in the aging microcirculation: new friends, new foes, and new clinical directions.
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Resveratrol Treatment Reverses Doxorubicin-Induced Vascular Dysfunction in Old Rat Mesenteric Arteries
Medicine and Science in Sports and Exercise. 44
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Skeletal muscle apoptotic signaling predicts thigh muscle volume and gait speed in community-dwelling older persons: an exploratory study.
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The impact of aging on mitochondrial function and biogenesis pathways in skeletal muscle of sedentary high- and low-functioning elderly individuals.
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Urinary Ctx-II Concentrations Are Elevated and Associated With Knee Pain and Function in Subjects With Acl Reconstruction
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2011
An Exploratory Analysis of the Effects of a Weight Loss Plus Exercise Program On Cellular Quality Control Mechanisms in Older Overweight Women
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Effects of a weight loss plus exercise program on physical function in overweight, older women: a randomized controlled trial.
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Expression of key regulators of mitochondrial biogenesis in growth hormone receptor knockout (GHRKO) mice is enhanced but is not further improved by other potential life-extending interventions.
The journals of gerontology. Series A, Biological sciences and medical sciences. 66(10):1062-76 [DOI] 10.1093/gerona/glr080. [PMID] 21788651.
2011
Inhibition of NF-kappaB-induced inflammatory responses by angiotensin II antagonists in aged rat kidney
Experimental Gerontology. 46(7):542-548
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Inhibition of NF-κB-induced inflammatory responses by angiotensin II antagonists in aged rat kidney.
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2011
Investigations of botanicals on food intake, satiety, weight loss and oxidative stress: study protocol of a double-blind, placebo-controlled, crossover study
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Investigations of botanicals on food intake, satiety, weight loss and oxidative stress: study protocol of a double-blind, placebo-controlled, crossover study.
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2011
Tfam, Mtdna and Their Interactions During Aging and Calorie Restriction (Cr) Diet.
Environmental and Molecular Mutagenesis. 52
2011
The Impact of Behavioral Intervention on Obesity Mediated Declines in Mobility Function: Implications for Longevity
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The impact of behavioral intervention on obesity mediated declines in mobility function: implications for longevity.
Journal of aging research. 2011 [DOI] 10.4061/2011/392510. [PMID] 22013527.
2010
Beneficial effects of a Q-ter based nutritional mixture on functional performance, mitochondrial function, and oxidative stress in rats
PLoS One. 5(5)
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2010
Calorie restriction for optimal cardiovascular aging: the weight of evidence.
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Dietary restriction: standing up for sirtuins.
Science (New York, N.Y.). 329(5995):1012-3; author reply 1013 [DOI] 10.1126/science.329.5995.1012. [PMID] 20798296.
2010
Effect of Intermittent Fasting for Five Consecutive Days On Exercise-Induced Muscle Damage in Humans
Medicine and Science in Sports and Exercise. 42
2010
Effects of Ace-Inhibition On Igf-1 and Igfbp-3 Concentrations in Older Adults With High Cardiovascular Risk Profile
Journal of Nutrition Health & Aging. 14:457-460
2010
Effects of age and sedentary lifestyle on skeletal muscle NF-kappaB signaling in men
The Journals Of Gerontology. Series A, Biological Sciences And Medical Sciences. 65(5):532-537
2010
Effects of age and sedentary lifestyle on skeletal muscle NF-kappaB signaling in men.
The journals of gerontology. Series A, Biological sciences and medical sciences. 65(5):532-7 [DOI] 10.1093/gerona/glp196. [PMID] 20045871.
2010
Hydrogen sulfide induces oxidative damage to RNA and DNA in a sulfide-tolerant marine invertebrate.
Physiological and biochemical zoology : PBZ. 83(2):356-65 [DOI] 10.1086/597529. [PMID] 19327040.
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Lifelong calorie restriction alleviates age-related oxidative damage in peripheral nerves.
Rejuvenation research. 13(1):65-74 [DOI] 10.1089/rej.2009.0892. [PMID] 20230280.
2010
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Biochimica et biophysica acta. 1800(3):235-44 [DOI] 10.1016/j.bbagen.2009.05.007. [PMID] 19450666.
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Models of accelerated sarcopenia: critical pieces for solving the puzzle of age-related muscle atrophy.
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2010
Multiple pathways to the same end: mechanisms of myonuclear apoptosis in sarcopenia of aging.
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2010
Myeloperoxidase levels and mortality in frail community-living elderly individuals.
The journals of gerontology. Series A, Biological sciences and medical sciences. 65(4):369-76 [DOI] 10.1093/gerona/glp183. [PMID] 20064836.
2010
New insights into the role of mitochondria in aging: mitochondrial dynamics and more.
Journal of cell science. 123(Pt 15):2533-42 [DOI] 10.1242/jcs.070490. [PMID] 20940129.
2010
Overexpression of Atg4B and Beclin-1 Enhances Liver Mitochondrial-Autophagy and Prevents the Age-Associated Ischemia/Reperfusion Injury To Mouse Liver
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Revealing system-level correlations between aging and calorie restriction using a mouse transcriptome.
Age (Dordrecht, Netherlands). 32(1):15-30 [DOI] 10.1007/s11357-009-9106-3. [PMID] 19590981.
2010
Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction.
Cell. 143(5):802-12 [DOI] 10.1016/j.cell.2010.10.002. [PMID] 21094524.
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Skeletal muscle autophagy and apoptosis during aging: effects of calorie restriction and life-long exercise.
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The emerging role of iron dyshomeostasis in the mitochondrial decay of aging.
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The hydrogen sulfide signaling system: changes during aging and the benefits of caloric restriction.
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2009
Age-related hearing loss in C57BL/6J mice is mediated by Bak-dependent mitochondrial apoptosis.
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2009
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2009
Bioenergetics and permeability transition pore opening in heart subsarcolemmal and interfibrillar mitochondria: effects of aging and lifelong calorie restriction.
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Cellular mechanisms of cardioprotection by calorie restriction: state of the science and future perspectives.
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Changes in IL-15 expression and death-receptor apoptotic signaling in rat gastrocnemius muscle with aging and life-long calorie restriction.
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Changes in lipid distribution during aging and its modulation by calorie restriction.
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Comparison of lifelong and late life exercise on oxidative stress in the cerebellum.
Neurobiology of aging. 30(6):903-9 [PMID] 17976863.
2009
Influence of calorie restriction on measures of age-related cognitive decline: role of increased physical activity.
The journals of gerontology. Series A, Biological sciences and medical sciences. 64(8):850-9 [DOI] 10.1093/gerona/glp060. [PMID] 19420296.
2009
Mice expressing an error-prone DNA polymerase in mitochondria display elevated replication pausing and chromosomal breakage at fragile sites of mitochondrial DNA.
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Sarcopenia of aging: underlying cellular mechanisms and protection by calorie restriction.
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A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice.
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2008
Effects of short-term GH supplementation and treadmill exercise training on physical performance and skeletal muscle apoptosis in old rats.
American journal of physiology. Regulatory, integrative and comparative physiology. 294(2):R558-67 [PMID] 18003794.
2008
Efficacy of Hydrogen Sulfide Signaling in Isolated Rat Aorta Changes With Age and Caloric Restriction
Arteriosclerosis Thrombosis and Vascular Biology. 28
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Exercise Training With Ageing Protects Against Ethanol Induced Myocardial Glutathione Homeostasis
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Journal of Neurochemistry. 104
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Lifelong exercise and mild (8%) caloric restriction attenuate age-induced alterations in plantaris muscle morphology, oxidative stress and IGF-1 in the Fischer-344 rat
Experimental Gerontology. 43(4):317-329
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Lifelong exercise and mild (8%) caloric restriction attenuate age-induced alterations in plantaris muscle morphology, oxidative stress and IGF-1 in the Fischer-344 rat.
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Localization of Abasic Sites and Single-Strand Breaks in Mitochondrial Dna From Brain of Aged Rat, Treated Or Not With Caloric Restriction Diet
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Long-term effects of caloric restriction or exercise on DNA and RNA oxidation levels in white blood cells and urine in humans.
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Modulation of age-induced apoptotic signaling and cellular remodeling by exercise and calorie restriction in skeletal muscle
Free Radical Biology and Medicine. 44(2):160-168
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Modulation of age-induced apoptotic signaling and cellular remodeling by exercise and calorie restriction in skeletal muscle.
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Modulation of GH/IGF-1 axis: potential strategies to counteract sarcopenia in older adults.
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Molecular mechanism of PPAR in the regulation of age-related inflammation.
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An Aging Interventions Testing Program: study design and interim report.
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American journal of physiology. Endocrinology and metabolism. 293(2):E507-14 [PMID] 17488806.
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Cardiac mitochondrial bioenergetics, oxidative stress, and aging.
American journal of physiology. Cell physiology. 292(6):C1983-92 [PMID] 17344313.
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Effects of life-long caloric restriction and voluntary exercise on age-related changes in levels of catecholamine biosynthetic enzymes and angiotensin II receptors in the rat adrenal medulla and hypothalamus.
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Evaluation of sex differences on mitochondrial bioenergetics and apoptosis in mice.
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Molecular mechanisms of life- and health-span extension: role of calorie restriction and exercise intervention.
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A method to determine RNA and DNA oxidation simultaneously by HPLC-ECD: greater RNA than DNA oxidation in rat liver after doxorubicin administration.
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Effects of caloric restriction and exercise on age-related, chronic inflammation assessed by C-reactive protein and interleukin-6.
The journals of gerontology. Series A, Biological sciences and medical sciences. 61(3):211-7 [PMID] 16567369.
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Frailty syndrome and skeletal muscle: results from the Invecchiare in Chianti study.
The American journal of clinical nutrition. 83(5):1142-8 [PMID] 16685058.
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Genetics, redox signaling, oxidative stress, and apoptosis in mammalian aging.
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Hepatic oxidative stress during aging: effects of 8% long-term calorie restriction and lifelong exercise.
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Impact of inflammation on the relationship among alcohol consumption, mortality, and cardiac events: the health, aging, and body composition study.
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2005
Age-associated increases in oxidative stress and antioxidant enzyme activities in cardiac interfibrillar mitochondria: implications for the mitochondrial theory of aging.
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American journal of physiology. Regulatory, integrative and comparative physiology. 288(5):R1288-96 [PMID] 15650125.
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Mechanisms of ageing and development. 126(6-7):783-93 [PMID] 15888333.
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Exercise by lifelong voluntary wheel running reduces subsarcolemmal and interfibrillar mitochondrial hydrogen peroxide production in the heart.
American journal of physiology. Regulatory, integrative and comparative physiology. 289(6):R1564-72 [PMID] 16051717.
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Science (New York, N.Y.). 309(5733):481-4 [PMID] 16020738.
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Muscle fiber specific apoptosis and TNF-alpha signaling in sarcopenia are attenuated by life-long calorie restriction.
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The role of apoptosis in age-related skeletal muscle atrophy
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The role of apoptosis in age-related skeletal muscle atrophy.
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Vulnerability of the mid aged rat myocardium to the age-induced oxidative stress: influence of exercise training on antioxidant defense system
Free Radical Biology and Medicine. 39(11):1211-1217
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Vulnerability of the mid aged rat myocardium to the age-induced oxidative stress: influence of exercise training on antioxidant defense system.
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WITHDRAWN: Life-long caloric restriction counteracts apoptotic effects of aging in the brain and bolsters the action of apoptosis inhibitors.
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Ageing and subcellular distribution of mitochondria: role of mitochondrial DNA deletions and energy production
Acta Physiologica. 182(4):333-341
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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.
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2004
C-reactive protein genotypes affect baseline, but not exercise training-induced changes, in C-reactive protein levels.
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Effects of dietary calcium restriction and acute exercise on the antioxidant enzyme system and oxidative stress in rat diaphragm.
American journal of physiology. Regulatory, integrative and comparative physiology. 287(1):R33-8 [PMID] 14764436.
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Lifelong aspirin supplementation as a means to extending life span.
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Linkage between insulin and the free radical theory of aging.
American journal of physiology. Regulatory, integrative and comparative physiology. 286(1):R20-1 [PMID] 14660473.
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Measurement of the 4,834-bp mitochondrial DNA deletion level in aging rat liver and brain subjected or not to caloric restriction diet
Annals of the New York Academy of Sciences. 1019:269-273
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Short-term caloric restriction and sites of oxygen radical generation in kidney and skeletal muscle mitochondria.
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Short-term CR decreases cardiac mitochondrial oxidant production but increases carbonyl content.
American journal of physiology. Regulatory, integrative and comparative physiology. 286(2):R254-9 [PMID] 14592935.
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A dietary supplement attenuates IL-6 and CRP after eccentric exercise in untrained males.
Medicine and science in sports and exercise. 35(12):2032-7 [PMID] 14652498.
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Effects of aging and caloric restriction on mitochondrial energy production in gastrocnemius muscle and heart
American Journal of Physiology-Regulatory Integrative and Comparative Physiology. 284(2):R474-R480
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Increased hepatic apoptosis during short-term caloric restriction is not associated with an enhancement in caspase levels.
Experimental gerontology. 38(8):897-903 [PMID] 12915211.
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Life-long calorie restriction in Fischer 344 rats attenuates age-related loss in skeletal muscle-specific force and reduces extracellular space.
Journal of applied physiology (Bethesda, Md. : 1985). 95(6):2554-62 [PMID] 12972444.
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Lifelong caloric restriction increases expression of apoptosis repressor with a caspase recruitment domain (ARC) in the brain.
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Method for measuring ATP production in isolated mitochondria: ATP production in brain and liver mitochondria of Fischer-344 rats with age and caloric restriction.
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Doxorubicin treatment in vivo causes cytochrome C release and cardiomyocyte apoptosis, as well as increased mitochondrial efficiency, superoxide dismutase activity, and Bcl-2:Bax ratio
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A hydroxyl radical-like species oxidizes cynomolgus monkey artery wall proteins in early diabetic vascular disease
The Journal Of Clinical Investigation. 107(7):853-860
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Aged rat hearts are not more susceptible to ischemia-reperfusion injury in vivo: role of glutathione
Mechanisms of Ageing and Development. 122(6):503-518
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Apoptosis and aging: role of the mitochondria
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Detecting oxidative modification of biomolecules with isotope dilution mass spectrometry: sensitive and quantitative assays for oxidized amino acids in proteins and tissues
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. 156(1):17-24
1996
Ischaemia-reperfusion induced alterations of mitochondrial function in hypertrophied rat heart
. 156(1):51-60
1995
Glutathione depletion in rested and exercised mice: biochemical consequence and adaptation
Archives of Biochemistry and Biophysics. 316(2):941-949
1994
Aging and exercise training in skeletal muscle: responses of glutathione and antioxidant enzyme systems
. 267(2):R439-R445
Temporal dynamics of the multi-omic response to endurance exercise training across tissues
. [DOI] 10.1101/2022.09.21.508770.

Grants

Sep 2022 ACTIVE
Functional Decline in Low Functioning Older Adults; Role of iron dysregulation
Role: Principal Investigator
Funding: NATL INST OF HLTH NIA
Jun 2022 ACTIVE
University of Florida Claude D. Pepper Older Americans Independence Center
Role: Other
Funding: NATL INST OF HLTH NIA
Jul 2021 – Jun 2022
Institutional Career Development Core
Role: Other
Funding: NATL INST OF HLTH NCATS
May 2020 ACTIVE
Translational Research Training on Aging and Mobility (TRAM)
Role: Faculty
Funding: NATL INST OF HLTH NIA
Apr 2020 ACTIVE
The Role and Mechanisms of Lipid and Lipoprotein Dysregulation in Sepsis
Role: Co-Investigator
Funding: NATL INST OF HLTH NIGMS
Sep 2019 ACTIVE
Nicotinamide riboside as an Enhancer of Exercise Therapy in hypertensive older adults: The NEET Trial
Role: Co-Investigator
Funding: NATL INST OF HLTH NIA
Jul 2019 ACTIVE
Molecular Biology in Burns and Trauma
Role: Other
Funding: NATL INST OF HLTH NIGMS
Aug 2018 ACTIVE
Senescence and Growth Differentiation Factors as Modifiers of Aging
Role: Co-Investigator
Funding: MAYO CLINIC via NATL INST OF HLTH NIA
Aug 2018 ACTIVE
INTERmittent pneumatic ComprEssion for Disablility rEversal in PAD: the INTERCEDE Trial
Role: Principal Investigator
Funding: NORTHWESTERN UNIV via NATL INST OF HLTH NIA
Jul 2018 – Jun 2022
Cardiac Dysfunction in Older Sepsis Survivors
Role: Other
Funding: AMER HEART ASSOCIATION
Jul 2018 – Jun 2022
Role of PFKFB3 in peripheral artery disease
Role: Other
Funding: AMER HEART ASSOCIATION
Jun 2018 – Jun 2022
OR-DRPD-ROF2018: The LIPid Intensive Drug therapy for Sepsis Pilot (LIPIDS-P) Trial
Role: Co-Investigator
Funding: UF RESEARCH
Jun 2018 – May 2020
PICS: A New Horizon for Surgical Critical Care
Role: Co-Investigator
Funding: NATL INST OF HLTH NIGMS
Apr 2018 ACTIVE
Biobehavioral mechanisms underlying symptoms and healing outcomes in older individuals with CVLU
Role: Co-Investigator
Funding: NATL INST OF HLTH NINR
Apr 2018 ACTIVE
Calf Muscle Mitochondrial Dysfunction and Impaired Autophagy in Peripheral Artery Disease
Role: Principal Investigator
Funding: NORTHWESTERN UNIV via AMER HEART ASSOCIATION
Apr 2018 – Mar 2021
NICotinomidE riboside with and without resveratrol to improve functioning in peripheral artery disease: The NICE Trial
Role: Principal Investigator
Funding: NORTHWESTERN UNIV via AMER HEART ASSOCIATION
Sep 2017 ACTIVE
The University of Florida Jacksonville Aging Studies Center (JAX-ASCENT)
Role: Co-Investigator
Funding: NATL INST OF HLTH NIA
Aug 2017 – Apr 2018
Resveratrol and exercise to treat functional limitations in late life
Role: Faculty
Funding: UNIV OF ALABAMA BIRMINGHAM via NATL INST OF HLTH NIA
Jul 2017 – May 2022
The effect of intermittent hemidiaphragm stimulation during surgery on mitochondrial function, single fiber contractile force and catabolic pathways in humans
Role: Co-Investigator
Funding: NATL INST OF HLTH NIAMS
Jun 2017 – May 2018
PICS: A New Horizon for Surgical Critical Care
Role: Co-Investigator
Funding: NATL INST OF HLTH NIGMS
Apr 2017 – Mar 2022
University of Florida Claude D. Pepper Older Americans Independence Center (OAIC)
Role: Other
Funding: NATL INST OF HLTH NIA
Dec 2016 ACTIVE
UF PASS: Regulation of exercise transducers
Role: Project Manager
Funding: NATL INST OF HLTH NIA
Dec 2016 – Nov 2021
Improve PAD PERformance with METformin: The PERMET Trial
Role: Principal Investigator
Funding: NORTHWESTERN UNIV via NATL INST OF HLTH NHLBI
Dec 2016 ACTIVE
MoTrPAC Consortium Coordinating Center
Role: Co-Investigator
Funding: NATL INST OF HLTH NIAMS
Sep 2016 – Aug 2020
The Role of Dysfunctional HDL in Sepsis
Role: Other
Funding: NATL INST OF HLTH NIGMS
Jun 2016 – Feb 2019
COCOA to improve walking performance in Peripheral Artery Disease: the COCOA-PAD Study
Role: Principal Investigator
Funding: NORTHWESTERN UNIV via NATL INST OF HLTH NIA
Jun 2016 – May 2017
PICS: A New Horizon for Surgical Critical Care
Role: Project Manager
Funding: NATL INST OF HLTH NIGMS
Apr 2016 – Mar 2017
Claude D Pepper Older Americans Independence Center
Role: Project Manager
Funding: NATL INST OF HLTH NIA
Aug 2015 – Apr 2020
Telmisartan Plus Exercise to Improve Functioning in PAD: The TELEX Trial
Role: Principal Investigator
Funding: NORTHWESTERN UNIV via NATL INST OF HLTH NHLBI
Jun 2015 – May 2016
PICS: A New Horizon for Surgical Critical Care
Role: Project Manager
Funding: NATL INST OF HLTH NIGMS
Apr 2015 – Jan 2021
Hematopoietic Stem Cell Dysfunction in the Elderly after Severe Injury
Role: Co-Investigator
Funding: NATL INST OF HLTH NIGMS
Apr 2015 – Jan 2019
Low intensity exercise intervention in peripheral artery disease
Role: Principal Investigator
Funding: NORTHWESTERN UNIV via NATL INST OF HLTH NHLBI
Apr 2015 – Mar 2016
Claude D. Pepper Older Americans Independence Center
Role: Project Manager
Funding: NATL INST OF HLTH NIA
Jun 2014 – May 2022
Obesity and Type-2 Diabetes: Bariatric Surgery Effects on Brain Function
Role: Co-Investigator
Funding: NATL INST OF HLTH NIDDK
May 2014 – Apr 2017
RESveratrol To Improve Outcomes in older People with PAD (the RESTORE Trial)
Role: Principal Investigator
Funding: NORTHWESTERN UNIV via NATL INST OF HLTH NIA
Jan 2014 – Dec 2018
MtDNA variant modifiers of cardiopulmonary responsiveness to physical activity
Role: Co-Investigator
Funding: NATL INST OF HLTH NHLBI
Sep 2013 – Dec 2019
REVIVE – Resveratrol to enhance vitality and vigor in elders
Role: Co-Investigator
Funding: NATL CTR FOR COMPLEM AND INTEGRATIVE HLT
Apr 2012 – Mar 2017
Mitophagy: A novel target to improve liver function after ischemia/reperfusion injury
Role: Project Manager
Funding: NATL INST OF HLTH NIDDK
Sep 2011 – Nov 2018
The LIFE Study
Role: Project Manager
Funding: NATL INST OF HLTH NIA
Jul 2007 – Aug 2016
Clinical and Translational Science Institute
Role: Project Manager
Funding: UF RESEARCH FOU

Education

Post-Doc, Internal Medicine
1995-1998 · Washington University School of Medicine Instructor Geriatrics & Gerontology
Fellow, Biochemistry and Aging
1993-1995 · University of Wisconsin
PhD in Biochemistry and Aging
1990-1995 · University of Illinois
Masters of Science in Applied Physiology
1988-1990 · University of Florida
Bachelors of Science in Applied Physiology
1986-1988 · University of Florida

Contact Details

Phones:
Business:
(352) 273-5735
Emails:
Business:
cleeuwen@ufl.edu
Addresses:
Business Mailing:
PO BOX 100107
Department of Physiology and Aging
GAINESVILLE FL 326100107
Business Street:
2004 MOWRY RD
Department of Physiology and Aging
GAINESVILLE FL 326103010