Geroscience and the trans-NIH Geroscience Interest Group, GSIG

Sierra, Felipe; Kohanski, Ron

doi:10.1007/s11357-016-9954-6

Cited by 135 publications

(104 citation statements)

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“…Recent advances in the field of geroscience have identified several hallmarks of aging that begin to explain the molecular mechanisms linking aging with disease (Lopez-Otin et al 2013;Kennedy et al 2014;Sierra and Kohanski 2017). Interventions that target these hallmarks of aging in laboratory animals are emerging as potential therapeutic strategies for delaying age-related disability and disease and increasing healthy lifespan .…”

Section: Introductionmentioning

confidence: 99%

A randomized controlled trial to establish effects of short-term rapamycin treatment in 24 middle-aged companion dogs

et al. 2017

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Age is the single greatest risk factor for most causes of morbidity and mortality in humans and their companion animals. As opposed to other model organisms used to study aging, dogs share the human environment, are subject to similar risk factors, receive comparable medical care, and develop many of the same age-related diseases humans do. In this study, 24 middle-aged healthy dogs received either placebo or a non-immunosuppressive dose of rapamycin for 10 weeks. All dogs received clinical and hematological exams before, during, and after the trial and echocardiography before and after the trial. Our results showed no clinical side effects in the rapamycin-treated group compared to dogs receiving the placebo. Echocardiography suggested improvement in both diastolic and systolic age-related measures of heart function (E/A ratio, fractional shortening, and ejection fraction) in the rapamycin-treated dogs. Hematological values remained within the normal range for all parameters studied; however, the mean corpuscular volume (MCV) was decreased in rapamycin-treated dogs. Based on these results, we will test rapamycin on a larger dog cohort for a longer period of time in order to validate its effects on cardiac function and to determine whether it can significantly improve healthspan and reduce mortality in companion dogs.

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Section: Introductionmentioning

confidence: 99%

A randomized controlled trial to establish effects of short-term rapamycin treatment in 24 middle-aged companion dogs

et al. 2017

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“…We suggest that the failure to utilize aged animals for preclinical studies of oral disease limits the clinical relevance of such studies. One goal of the Geroscience Initiative is to raise awareness of the importance of understanding the contribution of aging biology to age-related diseases (Sierra & Kohanski, 2017 Sumida & Hamakawa, 2001;Thevaranjan et al, 2017;Barrera et al, 2016;Khan et al, 2010;Yin & Chung, 2011;Parkinson et al, 2016;Lindroth & Park, 2013;Paul et al, 2015;Ballestar, 2011) R.I. Morimoto, J.E. Pessin, T.A.…”

Section: Aging and Diseases Of The Oral Cavitymentioning

confidence: 99%

“…The field of geroscience seeks to understand the biological mechanisms that underlie this relationship between aging and chronic disability and disease (Sierra & Kohanski, 2017;Kennedy & , S.L. Berger, A. Brunet, J. Campisi, A.M. Cuervo, E.S.…”

Section: Introductionmentioning

confidence: 99%

Oral health in geroscience: animal models and the aging oral cavity

Darveau

Kaeberlein

2017

GeroScience

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Age is the single greatest risk factor for many diseases, including oral diseases. Despite this, a majority of preclinical oral health research has not adequately considered the importance of aging in research aimed at the mechanistic understanding of oral disease. Here, we have attempted to provide insights from animal studies in the geroscience field and apply them in the context of oral health research. In particular, we discuss the relationship between the biology of aging and mechanisms of oral disease. We also present a framework for defining and utilizing age-appropriate rodents and present experimental design considerations, such as the number of age-points used and the importance of genetic background. While focused primarily on rodent models, alternative animal models that may be particularly useful for studies of oral health during aging, such as companion dogs and marmoset monkeys, are also discussed. We hope that such information will aid in the design of future preclinical studies of geriatric dental health, thus allowing more reliability for translation of such studies to age-associated oral disease in people.

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“…Due to the increased realization that understanding of the mechanisms underlying neurovascular dysfunction is critical for developing novel therapeutic interventions to prevent or treat AD, there is an increasing need in many laboratories to adapt methodologies to investigate neurovascular coupling responses in mouse models of aging and AD (Lacoste et al 2013;Ongali et al 2014;Papadopoulos et al 2016;Hamel et al 2016;Nicolakakis and Hamel 2011;Papadopoulos et al 2014). In this paper, published as part of the BMethods for Geroscience^series in the BTranslational Geroscience^initiative of the journal (Callisaya et al 2017;Kane et al 2017;Kim et al 2017;Liu et al 2017;Meschiari et al 2017;Perrott et al 2017;Shobin et al 2017;Ashpole et al 2017;Bennis et al 2017;Deepa et al 2017;Grimmig et al 2017;Hancock et al 2017;Konopka et al 2017;Podlutsky et al 2017;Sierra and Kohanski 2017;Tenk et al 2017;Ungvari et al 2017a;Ungvari et al 2017b;Urfer et al 2017a;Urfer et al 2017b), we present an easy-to-adapt protocol for assessment of neurovascular coupling responses in mice in both geroscience and AD research. As in these studies, experimental animals usually undergo behavioral testing prior to terminal experimentation; we aimed to provide a protocol that is relatively fast allowing investigators to process larger cohorts of animals.…”

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confidence: 99%

Demonstration of impaired neurovascular coupling responses in TG2576 mouse model of Alzheimer’s disease using functional laser speckle contrast imaging

et al. 2017

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Increasing evidence from epidemiological, clinical, and experimental studies indicates that cerebromicrovascular dysfunction and microcirculatory damage play critical roles in the pathogenesis of many types of dementia in the elderly, including both vascular cognitive impairment (VCI) and Alzheimer's disease. Vascular contributions to cognitive impairment and dementia (VCID) include impairment of neurovascular coupling responses/functional hyperemia (Bneurovascular uncoupling^). Due to the growing interest in understanding and pharmacologically targeting pathophysiological mechanisms of VCID, there is an increasing need for sensitive, easy-to-establish methods to assess neurovascular coupling responses. Laser speckle contrast imaging (LSCI) is a technique that allows rapid and minimally invasive visualization of changes in regional cerebromicrovascular blood perfusion. This type of imaging technique combines high resolution and speed to provide great spatiotemporal accuracy to measure moment-to-moment changes in cerebral blood flow induced by neuronal activation. Here, we provide detailed protocols for the successful measurement in neurovascular coupling responses in anesthetized mice equipped with a thinned-skull cranial window using LSCI. This method can be used to evaluate the effects of anti-aging or anti-AD treatments on cerebromicrovascular health.Keywords Neurovascular coupling . Functional hyperemia . Laser speckle contrast imaging . Laser speckle contrast analysis . LASCA . Laser speckle imaging . LSI Neurovascular uncoupling in aging and Alzheimer's diseaseIt is well recognized that the brain consumes more energy than any other human organ. Over 20% of the body's total energy requirements are spent to fuel the brain, which in turn only accounts for 2% of the total body mass. Moment-to-moment regulation of cerebral blood flow (CBF) is crucial since inadequate supply of glucose and oxygen to an active region of the brain GeroScience (2017) 39:465-473

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Geroscience and the trans-NIH Geroscience Interest Group, GSIG

Cited by 135 publications

References 11 publications

A randomized controlled trial to establish effects of short-term rapamycin treatment in 24 middle-aged companion dogs

A randomized controlled trial to establish effects of short-term rapamycin treatment in 24 middle-aged companion dogs

Oral health in geroscience: animal models and the aging oral cavity

Demonstration of impaired neurovascular coupling responses in TG2576 mouse model of Alzheimer’s disease using functional laser speckle contrast imaging

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