The biosure study: Influence of composition of diet and food consumption on longevity, degenerative diseases and neoplasia in wistar rats studied for up to 30 months post weaning

Roe, F. J. C.; P, Lee; Conybeare, G.; Kelly, Debra Lynch; Matter, B.E.; Prentice, D. E.; Tobin, Graham A.

doi:10.1016/0278-6915(95)80200-2

Cited by 76 publications

(80 citation statements)

References 151 publications

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“…Indeed, irrespective of the treatment, no difference was found in the food intake of young and old animals (data not shown), in agreement with other authors [103–105]. …”

Section: Discussionsupporting

confidence: 93%

Comparing the Behavioural Effects of Exogenous Growth Hormone and Melatonin in Young and Old Wistar Rats

Barceló

Nicolau

Gamundı́

et al. 2016

Oxidative Medicine and Cellular Longevity

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Growth hormone (GH) and melatonin are two hormones with quite different physiological effects. Curiously, their secretion shows parallel and severe age-related reductions. This has promoted many reports for studying the therapeutic supplementation of both hormones in an attempt to avoid or delay the physical, physiological, and psychological decay observed in aged humans and in experimental animals. Interestingly, the effects of the external administration of low doses of GH and of melatonin were surprisingly similar, as both hormones caused significant improvements in the functional capabilities of aged subjects. The present report aims at discerning the eventual difference between cognitive and motor effects of the two hormones when administered to young and aged Wistar rats. The effects were tested in the radial maze, a test highly sensitive to the age-related impairments in working memory and also in the rotarod test, for evaluating the motor coordination. The results showed that both hormones caused clear improvements in both tasks. However, while GH improved the cognitive capacity and, most importantly, the physical stamina, the effects of melatonin should be attributed to its antioxidant, anxiolytic, and neuroprotective properties.

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“…Indeed, irrespective of the treatment, no difference was found in the food intake of young and old animals (data not shown), in agreement with other authors [103–105]. …”

Section: Discussionsupporting

confidence: 93%

Comparing the Behavioural Effects of Exogenous Growth Hormone and Melatonin in Young and Old Wistar Rats

Barceló

Nicolau

Gamundı́

et al. 2016

Oxidative Medicine and Cellular Longevity

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“…Sustained, moderate reduction (20–40%) of calorie intake without malnutrition, known as calorie restriction (CR), reduces Aβ neuropathology compared to ad libitum (AL) feeding in several AD mouse models (Mouton et al, 2009; Patel et al, 2005; Wang et al, 2005), in addition to extending healthspan and lifespan in many species (Colman et al, 2009; Hart et al, 1999; Kealy et al, 2002; Klass, 1977; Mattison et al, 2012; McCay et al, 1935; Roe et al, 1995; Rous, 1914). The pathways that the brain endogenously employs to blunt Aβ pathology in response to CR are likely complex, and are not well characterized.…”

Section: Introductionmentioning

confidence: 99%

Reduction of β-amyloid and γ-secretase by calorie restriction in female Tg2576 mice

Schafer

Alldred

Lee

et al. 2015

Neurobiology of Aging

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Research indicates that female risk of developing Alzheimer’s disease (AD) is greater than that of males. Moderate reduction of calorie intake, known as calorie restriction (CR), reduces pathology in AD mouse models, and is a potentially translatable prevention measure for individuals at-risk for AD, as well as an important tool for understanding how the brain endogenously attenuates age-related pathology. Whether sex influences the response to CR remains unknown. In this study, we assessed the effect of CR on beta-amyloid peptide (Aβ) pathology and hippocampal CA1 neuron specific gene expression in the Tg2576 mouse model of cerebral amyloidosis. Relative to ad libitum (AL) feeding, CR feeding significantly reduced hippocampal Aβ burden in 15 month old female, but not age-matched male, Tg2576 mice. Sustained CR also significantly reduced expression of presenilin enhancer 2 (Psenen) and presenilin 1 (Ps1), components of the γ-secretase complex, in Tg2576 females. These results indicate that long-term CR significantly reduces age-dependent female Tg2576 Aβ pathology, which is likely to involve CR-mediated reductions in γ-secretase-dependent amyloid precursor protein (APP) metabolism.

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“…Feeding ad libitum, which actually means overfeeding 128 , 129 , significantly increases tumor incidences of the pituitary 130 , the mammary gland, and the lung in rats and of the liver in mice, but may decrease the incidence of uterine tumors in rats 131 . Overfeeding also increases the incidence and severity of degenerative diseases, including nephropathy 132 , which may impact on excretion of xenobiotics, and the incidence of myocarditis, polyarteritis, and prostatitis.…”

Section: Hazard Identificationmentioning

confidence: 99%

Successful Drug Development Despite Adverse Preclinical Findings Part 1: Processes to Address Issues and Most Important Findings

Ettlin¹,

Kuroda

Plassmann³

et al. 2010

J Toxicol Pathol

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Unexpected adverse preclinical findings (APFs) are not infrequently encountered during drug development. Such APFs can be functional disturbances such as QT prolongation, morphological toxicity or carcinogenicity. The latter is of particular concern in conjunction with equivocal genotoxicity results. The toxicologic pathologist plays an important role in recognizing these effects, in helping to characterize them, to evaluate their risk for man, and in proposing measures to mitigate the risk particularly in early clinical trials. A careful scientific evaluation is crucial while termination of the development of a potentially useful drug must be avoided. This first part of the review discusses processes to address unexpected APFs and provides an overview over typical APFs in particular classes of drugs. If the mode of action (MoA) by which a drug candidate produces an APF is known, this supports evaluation of its relevance for humans. Tailor-made mechanistic studies, when needed, must be planned carefully to test one or several hypotheses regarding the potential MoA and to provide further data for risk evaluation. Safety considerations are based on exposure at no-observed-adverse-effect levels (NOAEL) of the most sensitive and relevant animal species and guide dose escalation in clinical trials. The availability of early markers of toxicity for monitoring of humans adds further safety to clinical studies. Risk evaluation is concluded by a weight of evidence analysis (WoE) with an array of parameters including drug use, medical need and alternatives on the market. In the second part of this review relevant examples of APFs will be discussed in more detail.

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The biosure study: Influence of composition of diet and food consumption on longevity, degenerative diseases and neoplasia in wistar rats studied for up to 30 months post weaning

Cited by 76 publications

References 151 publications

Comparing the Behavioural Effects of Exogenous Growth Hormone and Melatonin in Young and Old Wistar Rats

Comparing the Behavioural Effects of Exogenous Growth Hormone and Melatonin in Young and Old Wistar Rats

Reduction of β-amyloid and γ-secretase by calorie restriction in female Tg2576 mice

Successful Drug Development Despite Adverse Preclinical Findings Part 1: Processes to Address Issues and Most Important Findings

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