Donald K Ingram

Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States

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Publications (377)1721.51 Total impact

  • Michael J Keenan · Maria L Marco · Donald K Ingram · Roy J Martin ·
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    ABSTRACT: Dietary resistant starch impact on intestinal microbiome and improving healthspan is the topic of this review. In the elderly population, dietary fiber intake is lower than recommended. Dietary resistant starch as a source of fiber produces a profound change in gut microbiota and fermentation in animal models of aging. Dietary resistant starch has the potential for improving healthspan in the elderly through multiple mechanisms as follows: (1) enhancing gut microbiota profile and production of short-chain fatty acids, (2) improving gut barrier function, (3) increasing gut peptides that are important in glucose homeostasis and lipid metabolism, and (4) mimicking many of the effects of caloric restriction including upregulation of genes involved in xenobiotic metabolism.
    Age 09/2015; 37(5):98. DOI:10.1007/s11357-015-9817-6 · 3.45 Impact Factor
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    ABSTRACT: Over the past decade, a large number of discoveries have shown that interventions (genetic, pharmacological, and nutritional) increase the lifespan of invertebrates and laboratory rodents. Therefore, the possibility of developing antiaging interventions for humans has gone from a dream to a reality. However, it has also become apparent that we need more information than just lifespan to evaluate the translational potential of any proposed antiaging intervention to humans. Information is needed on how an intervention alters the "healthspan" of an animal, that is, how the physiological functions that change with age are altered. In this report, we describe the utility and the limitations of assays in mice currently available for measuring a wide range of physiological functions that potentially impact quality of life. We encourage investigators and reviewers alike to expect at minimum an overall assessment of health in several domains across several ages before an intervention is labeled as "increasing healthspan." In addition, it is important that investigators indicate any tests in which the treated group did worse or did not differ statistically from controls because overall health is a complex phenotype, and no intervention discovered to date improves every aspect of health. Finally, we strongly recommend that functional measurements be performed in both males and females so that sex differences in the rate of functional decline in different domains are taken into consideration. Published by Oxford University Press on behalf of the Gerontological Society of America 2015.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 08/2015; DOI:10.1093/gerona/glv080 · 5.42 Impact Factor
  • George S Roth · Donald K Ingram ·
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    ABSTRACT: After nearly a century of rigorous investigation and testing, dietary caloric restriction (CR) remains the most robust and reproducible method for slowing aging and maintaining health, function, and vitality. This intervention has been applied to species across the evolutionary spectrum, but for a number of reasons, practical applicability to humans has been questioned. To overcome these issues, we initiated the field of CR mimetics in 1998 and have observed its development into a full-fledged antiaging industry. Basically, strategies that enable individuals to obtain the biological benefits of CR without reducing actual food intake can be considered CR mimetics, whether functional, pharmaceutical, nutraceutical, or other. Some of the best known candidates include resveratrol and related agents, the antidiabetic drug metformin, and rapamycin and other mTOR regulators. While the mechanisms of action vary, these and essentially all CR mimetic candidates work through at least some of the same pathways as actual CR. While the entire field continues to evolve rapidly, the current status will be reviewed here, with particular focus on recent developments, the most practical relevance and applicability for potential consumers, and new strategies for the future. © 2015 New York Academy of Sciences.
    Annals of the New York Academy of Sciences 07/2015; DOI:10.1111/nyas.12834 · 4.38 Impact Factor
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    ABSTRACT: Objective Metabolic syndrome (MetS) risk increases significantly during menopause and remains elevated postmenopause. Several botanicals, including blueberries (BB), have been shown to delay MetS progression, but few studies have been conducted in postmenopausal animal models. Here, the effects of BB supplementation on obese postmenopausal mice using a chemically induced menopause model were examined.Methods After induction of menopause, mice were fed a high-fat diet or the same diet supplemented with 4% BB powder for 12 weeks. Body weight and body composition were measured, and mice were subjected to glucose and insulin tolerance tests. Serum triglycerides and adiponectin were measured, and liver histology and hepatic gene expression were assessed.ResultsMenopausal and BB-supplemented mice had significantly higher body weights and fat mass than control mice, while menopausal mice had impaired glucose tolerance and higher serum triglycerides when compared with control and BB-supplemented mice. Menopausal mice also had hepatic steatosis that was prevented by BB supplementation and correlated with expression of genes involved in hepatic fatty acid oxidation.ConclusionsBB supplementation prevents the glucose intolerance and hepatic steatosis that occur in obese postmenopausal mice, and these effects are independent of body weight.
    Obesity 01/2015; 23(3). DOI:10.1002/oby.20926 · 3.73 Impact Factor
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    Journal of the American Veterinary Medical Association 01/2015; 246(1):67-75. DOI:10.2460/javma.246.1.67 · 1.56 Impact Factor
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    Journal of the American Veterinary Medical Association 01/2015; 246(1):77-89. DOI:10.2460/javma.246.1.77 · 1.56 Impact Factor
  • Donald K. Ingram · George S. Roth ·
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    ABSTRACT: Strong consensus exists regarding the most robust environmental intervention for attenuating aging processes and increasing healthspan and lifespan: calorie restriction (CR). Over several decades, this paradigm has been replicated in numerous nonhuman models, and has been expanded over the last decade to formal, controlled human studies of CR. Given that long-term CR can create heavy challenges to compliance in human diets, the concept of a calorie restriction mimetic (CRM) has emerged as an active research area within gerontology. In past presentations on this subject, we have proposed that a CRM is a compound that mimics metabolic, hormonal, and physiological effects of CR, activates stress response pathways observed in CR and enhances stress protection, produces CR-like effects on longevity, reduces age-related disease, and maintains more youthful function, all without significantly reducing food intake, at least initially. Over 16 years ago, we proposed that glycolytic inhibition could be an effective strategy for developing CRM. The main argument here is that inhibiting energy utilization as far upstream as possible provides the highest chance of generating a broad spectrum of CR-like effects when compared to targeting a singular molecular target downstream. As an initial candidate CRM, 2-deoxyglucose, a known anti-glycolytic, was shown to produce a remarkable phenotype of CR, but further investigation found that this compound produced cardiotoxicity in rats at the doses we had been using. There remains interest in 2DG as a CRM but at lower doses. Beyond the proposal of 2DG as a candidate CRM, the field has grown steadily with many investigators proposing other strategies, including novel anti-glycolytics. Within the realm of upstream targeting at the level of the digestive system, research has included bariatric surgery, inhibitors of fat digestion/absorption, and inhibitors of carbohydrate digestion. Research focused on downstream sites has included insulin receptors, IGF-1 receptors, sirtuin activators, inhibitors of mTOR, and polyamines. In the current review we discuss progress made involving these various strategies and comment on the status and future for each within this exciting research field.
    Ageing Research Reviews 12/2014; 20. DOI:10.1016/j.arr.2014.11.005 · 4.94 Impact Factor
  • Erin Heitman · Donald K Ingram ·
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    ABSTRACT: Objectives The aim of this review was to provide an overview of studies conducted to determine the effects of chlorogenic acid (CGA) on cognition and neurological health. Methods A literature search was conducted using PubMed and various search terms including chlorogenic acid, CGA, CA, memory, neuroscience, cognition, nutrition, antioxidant, pharmacokinetics, neuroprotection, and neurodegeneration. Results Many studies have linked CGA consumption to a wide range of health benefits, including neuroprotection, cardioprotection, weight loss, chemopreventive properties, anti-inflammatory activity, decreased blood pressure, decreased diet-induced insulin resistance, decreased blood pressure, anxiolytic effects, and antihyperalgesic effects. Pre-clinical and clinical studies both provide evidence that CGA supplementation could protect against neurological degeneration and the resulting diseases associated with oxidative stress in the brain; however, no formal, well-controlled studies have been performed to date. Discussion Recent research suggests that dietary consumption of CGA could produce a wide range of health benefits and physiological effects. There is also mounting evidence that the consumption of polyphenols, including CGA, in the diet could reduce the risk of developing neurodegenerative conditions. Further studies should be conducted with a focus on the effects of CGA on cognition and the nervous system and employing well-designed clinical studies.
    Nutritional Neuroscience 08/2014; DOI:10.1179/1476830514Y.0000000146 · 2.27 Impact Factor
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    ABSTRACT: Heme oxygenase-1 (HO-1) encoded by the HMOX1 gene is a 32 kDa stress protein that catabolizes heme to biliverdin, free iron and carbon monoxide. Glial HO-1 is over-expressed in the CNS of subjects with Alzheimer's disease (AD), Parkinson's disease (PD) and multiple sclerosis (MS). The HMOX1 gene is exquisitely sensitive to oxidative stress and is induced in brain and other tissues in various models of disease and trauma. Induction of the glial HMOX1 gene may lead to pathological brain iron deposition, intracellular oxidative damage and bioenergetic failure in AD and other human CNS disorders such as PD and MS. Therefore, targeted suppression of glial HO-1 hyperactivity may prove to be a rational and effective therapeutic intervention in AD and related neurodegenerative disorders. In the present study, we report the effects of QC-47, QC-56 and OB-28, novel azole-based competitive and reversible inhibitors of HO-1, on oxidative damage to whole cell and mitochondrial compartments in rat astrocytes transfected with the HMOX1 gene. We also report the effect of OB-28 on the behavior and neuropathology of APPswe/PS1∆E9 mice. OB-28 was found to reduce oxidative damage to whole cell and mitochondrial compartments in rat astrocytes transfected with the HMOX1 gene. Moreover, OB-28 was found to significantly counter behavioural deficits and neuropathological alterations in APPswe/PS1∆E9 mice. Attenuation of AD-associated behavioural deficits and neuropathological changes suggests that HO-1 may be a promising target for neuro-protective intervention in AD and other neurodegenerative diseases.This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 08/2014; DOI:10.1111/jnc.12927 · 4.28 Impact Factor
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    Journal of Diabetes 06/2014; 6(6). DOI:10.1111/1753-0407.12178 · 1.93 Impact Factor
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    ABSTRACT: We previously reported that moderate calorie restriction (CR) has minimal impact on testicular gene expression in young adult rhesus macaques, and no obvious negative impact on semen quality or plasma testosterone levels. We now extend these findings by examining the influence of CR on various aspects of the reproductive axis of older males, including 24-h circulating testosterone levels, testicular gene expression, and testicular morphology. Young adult and old adult male rhesus macaques were subjected to either 30 % CR for 5-7 years, or were fed a standard control diet. Analysis of the 24-h plasma testosterone profiles revealed a significant age-associated decline, but no evidence for CR-induced suppression in either the young or old males. Similarly, expression profiling of key genes associated with testosterone biosynthesis and Leydig cell maintenance showed no significant CR-induced changes in either the young or old animals. The only evidence for CR-associated negative effects on the testis was detected in the old animals at the histological level; when old CR animals were compared with their age-matched controls, there was a modest decrease in seminiferous tubule diameter and epithelium height, with a concomitant increase in the number of depleted germ cell lines. Reassuringly, data from this study and our previous study suggest that moderate CR does not negatively impact 24-h plasma testosterone profiles or testicular gene expression. Although there appear to be some minor CR-induced effects on testicular morphology in old animals, it is unclear if these would significantly compromise fertility.
    Age 02/2014; 36(1):183-197. DOI:10.1007/s11357-013-9563-6 · 3.45 Impact Factor
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    ABSTRACT: Previous studies have shown that cyclic nucleotide phosphodiesterase type 5 (PDE5) inhibition with the drugs sildenafil and vardenafil can enhance spatial performance and object recognition in rodent models of learning and memory. We review recent studies on PDE5 inhibition and report novel data that specifically tests the systemic effects of both pharmacological agents in aged rats using two different spatial learning/memory paradigms. The 14-unit T-maze was used as a test of egocentric spatial processing that requires rats to learn a series of left/right turns to avoid mild footshock. The Morris water maze is a test of allocentric spatial learning that requires the acquisition of place information to localize a hidden platform relative to distal room cues. In both cases, acquisition (i.e., learning performance) was not improved, however after a one week drug washout period, aged animals demonstrated improved spatial memory retention compared to aged controls, ruling out simple performance effects. These findings are discussed in relation to recent reports on the use of PDE inhibitors to treat Alzheimer's disease (AD) dementia and age-related memory impairments. While some report promising pre-clinical results, others note that PDE5 may not be an appropriate target in AD due to a lack of localization within critical brain structures where therapeutic activity is needed. Despite these limitations, PDE5 inhibition may produce beneficial effects via several mechanisms that target predisposing risk factors leading to increased incidence of memory impairment in aged individuals and influence memory consolidation mechanisms that preserve long-term retention of cognitive information.
    Neurorehabilitation 11/2013; 34(1). DOI:10.3233/NRE-131022 · 1.12 Impact Factor
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    ABSTRACT: Resistant starch (RS) is a dietary fiber that exerts multiple beneficial effects. The current study explored the effects of dietary RS on selected brain and behavioral functions in adult and aged rodents. Because glucokinase (GK) expression in hypothalamic arcuate nucleus and area postrema of the brainstem is important for brain glucose sensing, GK mRNA was measured by brain nuclei microdissection and PCR. Adult RS-fed rats had a higher GK mRNA than controls in both brain nuclei, an indicator of improved brain glucose sensing. Next, we tested whether dietary RS improve selected behaviors in aged mice. RS-fed aged mice exhibited (i) an increased eating responses to fasting, a behavioral indicator of improvement in aged brain glucose sensing; (ii) a longer latency to fall from an accelerating rotarod, a behavioral indicator of improved motor coordination; and (iii) a higher serum active glucagon-like peptide-1 (GLP-1). Then, GLP-1 receptor null (GLP-1RKO) mice were used to test the role of GLP-1 in brain glucose sensing, and they exhibited impaired eating responses to fasting. We conclude that in rodents (i) dietary RS improves two important indicators of brain function: glucose sensing and motor coordination, and (ii) GLP-1 is important in the optimal feeding response to a fast.
    Molecular Nutrition & Food Research 11/2013; 57(11). DOI:10.1002/mnfr.201300135 · 4.60 Impact Factor
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    ABSTRACT: Despite a wealth of clinical data showing an association between inflammation and degenerative disorders in the elderly, the immune sensors that causally link systemic inflammation to aging remain unclear. Here we detail a mechanism by which the Nlrp3 inflammasome controls systemic low-grade age-related "sterile" inflammation in both periphery and brain independently of the noncanonical caspase-11 inflammasome. Ablation of Nlrp3 inflammasome protected mice from age-related increases in the innate immune activation, alterations in CNS transcriptome, and astrogliosis. Consistent with the hypothesis that systemic low-grade inflammation promotes age-related degenerative changes, the deficient Nlrp3 inflammasome-mediated caspase-1 activity improved glycemic control and attenuated bone loss and thymic demise. Notably, IL-1 mediated only Nlrp3 inflammasome-dependent improvement in cognitive function and motor performance in aged mice. These studies reveal Nlrp3 inflammasome as an upstream target that controls age-related inflammation and offer an innovative therapeutic strategy to lower Nlrp3 activity to delay multiple age-related chronic diseases.
    Cell metabolism 10/2013; 18(4):519-532. DOI:10.1016/j.cmet.2013.09.010 · 17.57 Impact Factor
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    ABSTRACT: Metformin is a drug commonly prescribed to treat patients with type 2 diabetes. Here we show that long-term treatment with metformin (0.1% w/w in diet) starting at middle age extends healthspan and lifespan in male mice, while a higher dose (1% w/w) was toxic. Treatment with metformin mimics some of the benefits of calorie restriction, such as improved physical performance, increased insulin sensitivity, and reduced low-density lipoprotein and cholesterol levels without a decrease in caloric intake. At a molecular level, metformin increases AMP-activated protein kinase activity and increases antioxidant protection, resulting in reductions in both oxidative damage accumulation and chronic inflammation. Our results indicate that these actions may contribute to the beneficial effects of metformin on healthspan and lifespan. These findings are in agreement with current epidemiological data and raise the possibility of metformin-based interventions to promote healthy aging.
    Nature Communications 07/2013; 4:2192. DOI:10.1038/ncomms3192 · 11.47 Impact Factor

  • Bioactives in Fruit, 06/2013: pages 251-271; , ISBN: 9780470674970
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    ABSTRACT: Activity patterns and sleep-wake cycles are among the physiological processes that change most prominently as animals age, and are often good indicators of healthspan. In this study, we used the video-based high-resolution Behavioral Monitoring System (BMS) to monitor the daily activity cycle of tephritid fruit flies Anastrepha ludens over their lifetime. Surprisingly, there was no dramatic change in activity profile with respect to age if flies were consistently fed with a nutritionally balanced diet. However, if flies were fed with sugar-only diet, their activity profile decreased in amplitude at old age, suggesting that suboptimal diet affected activity patterns, and its detrimental effect may not manifest itself until the animal ages. Moreover, by simulating different modes of behavior monitoring with a range of resolution and comparing the resulting conclusions, we confirmed the superior performance of video-based monitoring using high-resolution BMS in accurately representing activity patterns in an insect model.
    Scientific Reports 05/2013; 3:1773. DOI:10.1038/srep01773 · 5.58 Impact Factor
  • Henryk F Urbanski · Julie A Mattison · George S Roth · Donald K Ingram ·
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    ABSTRACT: The adrenal steroid, dehydroepiandrosterone sulfate (DHEAS), is generally regarded as being a reliable endocrine marker of aging, because in humans and nonhuman primates its circulating concentrations are very high during young adulthood, and the concentrations then decline markedly during aging. Despite promising results from early studies, we were recently surprised to find that caloric restriction (CR) did little to prevent or delay the decline of DHEAS concentrations in old rhesus macaques. Here we summarize the use of circulating DHEAS concentrations as a biomarker of aging in CR studies and suggest reasons for its limited value. Although DHEAS can reliably predict aging in animals maintained on a standard diet, dietary manipulations may affect liver enzymes involved in the metabolism of steroid hormones. Consequently, in CR studies the reliability of using DHEAS as a biomarker of aging may be compromised.
    Experimental gerontology 01/2013; 48(10). DOI:10.1016/j.exger.2013.01.001 · 3.49 Impact Factor
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    ABSTRACT: Calorie restriction (CR), a reduction of 10–40% in intake of a nutritious diet, is often reported as the most robust non-genetic mechanism to extend lifespan and healthspan. CR is frequently used as a tool to understand mechanisms behind ageing and age-associated diseases. In addition to and independently of increasing lifespan, CR has been reported to delay or prevent the occurrence of many chronic diseases in a variety of animals. Beneficial effects of CR on outcomes such as immune function, motor coordination and resistance to sarcopenia in rhesus monkeys have recently been reported. We report here that a CR regimen implemented in young and older age rhesus monkeys at the National Institute on Aging (NIA) has not improved survival outcomes. Our findings contrast with an ongoing study at the Wisconsin National Primate Research Center (WNPRC), which reported improved survival associated with 30% CR initiated in adult rhesus monkeys (7–14 years) and a preliminary report with a small number of CR monkeys. Over the years, both NIA and WNPRC have extensively documented beneficial health effects of CR in these two apparently parallel studies. The implications of the WNPRC findings were important as they extended CR findings beyond the laboratory rodent and to a long-lived primate. Our study suggests a separation between health effects, morbidity and mortality, and similar to what has been shown in rodents, study design, husbandry and diet composition may strongly affect the life-prolonging effect of CR in a long-lived nonhuman primate.
    Nature 08/2012; 489(7415):318-21. DOI:10.1038/nature11432 · 41.46 Impact Factor

Publication Stats

18k Citations
1,721.51 Total Impact Points


  • 2007-2015
    • Pennington Biomedical Research Center
      • Nutritional Neuroscience and Aging Laboratory
      Baton Rouge, Louisiana, United States
  • 2008-2014
    • Louisiana State University
      Baton Rouge, Louisiana, United States
    • University of Tsukuba
      Tsukuba, Ibaraki, Japan
  • 1981-2014
    • National Institute on Aging
      • • Laboratory of Experimental Gerontology (LEG)
      • • Laboratory of Cellular and Molecular Biology (LCMB)
      • • Molecular Genetics Section
      • • Laboratory of Behavioral Neuroscience
      Baltimore, Maryland, United States
  • 2010
    • Northern Inyo Hospital
      BIH, California, United States
  • 1990-2007
    • National Institutes of Health
      • • Laboratory of Experimental Gerontology (LEG)
      • • Section on Molecular Genetics of Immunity
      베서스다, Maryland, United States
  • 2004
    • University of Texas at San Antonio
      San Antonio, Texas, United States
    • Indiana University-Purdue University Indianapolis
      • Institute of Psychiatric Research
      Indianapolis, IN, United States
  • 2001
    • Southern Illinois University Carbondale
      • Department of Physiology
      Carbondale, IL, United States
  • 2000
    • University of Maryland, Baltimore
      • Department of Medicine
      Baltimore, Maryland, United States
  • 1985-1997
    • Johns Hopkins University
      Baltimore, Maryland, United States
    • Molecular and Cellular Biology Program
      • Laboratory of Cellular and Molecular Biology
      Seattle, Washington, United States
  • 1996
    • Weizmann Institute of Science
    • CRC Press Online
      Boca Raton, Florida, United States
  • 1984-1994
    • Institut de Génétique et de Biologie Moléculaire et Cellulaire
      Strasburg, Alsace, France
    • Dupont
      Делаварский, Ohio, United States
  • 1993
    • University of Baltimore
      Baltimore, Maryland, United States
    • University of Missouri
      Columbia, Missouri, United States
  • 1989
    • The Ohio State University
      • Department of Pathology
      Columbus, OH, United States
  • 1983
    • Medical University of South Carolina
      • Department of Psychiatry and Behavioral Sciences
      Charleston, South Carolina, United States
  • 1980-1981
    • The Jackson Laboratory
      Bar Harbor, Maine, United States