circRNAs expressed in human peripheral blood are associated with human aging phenotypes, cellular senescence and mouse lifespan
AbstractCircular RNAs (circRNAs) are an emerging class of non-coding RNA molecules that are thought to regulate gene expression and human disease. Despite the observation that circRNAs are known to accumulate in older organisms and have been reported in cellular senescence, their role in aging remains relatively unexplored. Here, we have assessed circRNA expression in aging human blood and followed up age-associated circRNA in relation to human aging phenotypes, mammalian longevity as measured by mouse median strain lifespan and cellular senescence in four different primary human cell types. We found that circRNAscircDEF6,...
Source: AGE - December 6, 2019 Category: Geriatrics Source Type: research

Proceedings from the Albert Charitable Trust Inaugural Workshop on white matter and cognition in aging
This report provides a synopsis of the presentations and discussions b y the participants, including the existing knowledge gaps and the delineation of the next steps towards advancing our understanding of white matter injury and age-related cognitive decline. Workshop discussions and consensus resulted in action by The Albert Trust to (1) increase support from biannua l to annual “White Matter and Cognition” workshops; (2) provide funding for two collaborative, novel research grants annually submitted by meeting participants; and (3) coordinate the formation of the “Albert Research Institute for White Ma...
Source: AGE - December 6, 2019 Category: Geriatrics Source Type: research

The role of exercise in the reversal of IGF-1 deficiencies in microvascular rarefaction and hypertension
AbstractHypertension has been linked with peripheral and central reductions in vascular density, and with devastating effects on brain function. However, the underlying mechanisms in the relationship between blood pressure and cognitive impairment have yet to be fully elucidated. Here, we review compelling evidence from two lines of inquiry: one that links microvascular rarefaction with insulin-like growth factor 1 (IGF-1) deficiencies, and another which posits that vascular dysfunction precedes hypertension. Based on the findings from experimental and clinical studies, we propose that these lines of evidence converge, and...
Source: AGE - December 5, 2019 Category: Geriatrics Source Type: research

The smell of longevity: a combination of Volatile Organic Compounds (VOCs) can discriminate centenarians and their offspring from age-matched subjects and young controls
AbstractAging is characterized by dynamic changes at metabolic level that lead to modifications in the composition of the metabolome. Since the identification of biomarkers that can discriminate people of different age and health status has recently attracted a great interest, we wondered whether age-specific changes in the metabolome could be identified and serve as new and informative biomarkers of aging and longevity. In the last few years, a specific branch of metabonomics devoted to the study of volatile organic compounds (VOCs) has been developed. To date, little is known about the profile of specific VOCs in healthy...
Source: AGE - December 5, 2019 Category: Geriatrics Source Type: research

Microvascular contributions to age-related macular degeneration (AMD): from mechanisms of choriocapillaris aging to novel interventions
AbstractAging of the microcirculatory network plays a central role in the pathogenesis of a wide range of age-related diseases, from heart failure to Alzheimer ’s disease. In the eye, changes in the choroid and choroidal microcirculation (choriocapillaris) also occur with age, and these changes can play a critical role in the pathogenesis of age-related macular degeneration (AMD). In order to develop novel treatments for amelioration of choriocapillaris aging and prevention of AMD, it is essential to understand the cellular and functional changes that occur in the choroid and choriocapillaris during aging. In this re...
Source: AGE - December 4, 2019 Category: Geriatrics Source Type: research

Ellagic acid prolongs the lifespan of Drosophila melanogaster
AbstractWild-type Canton-S flies ofDrosophila melanogaster were treated with ellagic acid at 100  μM and 200 μM concentrations. Longevity assay showed male flies fed with 200 μM ellagic acid displayed longer mean lifespan and maximum lifespan than control flies. Female flies fed with 200 μM ellagic acid laid less number of eggs than control. The eclosion time was less in female flies fed with 200 μM ellagic acid. Ellagic acid fed female flies performed better than male flies and control flies for heat shock tolerance and starvation stress. Male flies treated with 100 μM ellagic acid recover...
Source: AGE - November 30, 2019 Category: Geriatrics Source Type: research

Tryptophan metabolism is differently regulated between large and small dogs
AbstractCompanion dogs have recently been promoted as an animal model for the study of aging due to their similar disease profile to humans, the sophistication of health assessment and disease diagnosis, and the shared environments with their owners. In addition, dogs show an interesting life history trait pattern where smaller individuals are up to two-fold longer lived than their larger counterparts. While some of the mechanisms underlying this size and longevity trade-off are strongly suspected (i.e., growth hormone/IGF-I), there are likely a number of undiscovered mechanisms as well. Accordingly, we have completed a la...
Source: AGE - November 29, 2019 Category: Geriatrics Source Type: research

Acclimation to a thermoneutral environment abolishes age-associated alterations in heart rate and heart rate variability in conscious, unrestrained mice
AbstractMice are among the most widely used translational models of cardiovascular aging and offer a method to quickly assess lifespan changes in a controlled environment. The standard laboratory temperature (20 –22 °C), however, imposes a cold stress on mice that causes an increase in sympathetic nervous system–mediated activation of brown adipose tissue (BAT) to maintain a core body temperature of 36–37 °C. Thus, while physiologic data obtained recapitulate human physiology to a certain degree, in terpretations of previous research in mice may have been contaminated by a cold stress, due to hous...
Source: AGE - November 27, 2019 Category: Geriatrics Source Type: research

Older adults demonstrate interlimb transfer of reactive gait adaptations to repeated unpredictable gait perturbations
In this study, we investigate if age-related differences in stability following gait perturbations remain when all participants walk with equivalent stability. We also examine if interlimb transfer of gait adaptations are observed in healthy older adults, by examining if adaptation to repeated perturbations of one leg can benefit stability recovery when the other leg is perturbed. During walking at their stability-normalised walking speeds (young: 1.32 ± 0.07 m/s; older: 1.31 ± 0.13 m/s; normalised to an average margin of stability of 0.05 m), 30 young and 28 older healthy adults experienced ten unpredictable...
Source: AGE - November 27, 2019 Category: Geriatrics Source Type: research

Correction to: Genetic conversion of proliferative astroglia into neurons after cerebral ischemia: a new therapeutic tool for the aged brain?
Unfortunately, the name of the second author was incorrectly captured in the published online paper. (Source: AGE)
Source: AGE - November 27, 2019 Category: Geriatrics Source Type: research

Age- and sex-specific effects in paravertebral surface electromyographic back extensor muscle fatigue in chronic low back pain
This study sought to investigate whether the median frequency (MF) surface electromyographic (SEMG) back muscle fatigue method —a proxy for glycolytic muscle metabolism—would be able to detect age- and sex-specific differences in neuromuscular and muscle metabolic functions in individuals with cLBP in a reliable way, and whether it would be as sensitive as when used on healthy individuals. With participants seated on a dynamometer (20° trunk anteflexion), paraspinal SEMG activity was recorded bilaterally from the multifidus (L5), longissimus (L2), and iliolumbalis (L1) muscles during isometric, sustained ba...
Source: AGE - November 27, 2019 Category: Geriatrics Source Type: research

Astrocyte senescence contributes to cognitive decline
(Source: AGE)
Source: AGE - November 26, 2019 Category: Geriatrics Source Type: research

Aging induced by D-galactose aggravates cardiac dysfunction via exacerbating mitochondrial dysfunction in obese insulin-resistant rats
AbstractThe prevalence of obesity and an aging population are increasing worldwide. Both obesity and aging are independently known to be associated with cardiac dysfunction. However, in obese insulin-resistant subjects, the effects of aging on metabolic status and cardiac and mitochondrial functions are not completely understood. We hypothesized that in the obese insulin-resistant condition, aging induced by D-galactose increases cardiac senescence markers and aggravates the impairment of metabolic parameters, cardiac and mitochondrial function, and increases oxidative stress, inflammation, apoptosis, and autophagy. Sixty-...
Source: AGE - November 25, 2019 Category: Geriatrics Source Type: research

Topical rapamycin reduces markers of senescence and aging in human skin: an exploratory, prospective, randomized trial
AbstractAging is a major risk factor for the majority of human diseases, and the development of interventions to reduce the intrinsic rate of aging is expected to reduce the risk for age-related diseases including cardiovascular disease, cancer, and dementia. In the skin, aging manifests itself in photodamage and dermal atrophy, with underlying tissue reduction and impaired barrier function. To determine whether rapamycin, an FDA-approved drug targeting the mechanistic target of rapamycin (mTOR) complex, can reduce senescence and markers of aging in human skin, an exploratory, placebo-controlled, interventional trial was c...
Source: AGE - November 25, 2019 Category: Geriatrics Source Type: research

Serum beta-secretase 1 (BACE1) activity as candidate biomarker for late-onset Alzheimer ’s disease
AbstractBeta-secretase (BACE1) is a key enzyme in the formation of amyloid- β; its activity/concentration is increased in brain and cerebrospinal fluid of patients with late-onset Alzheimer’s disease (LOAD). Since BACE1 was found also in blood, we evaluated its potential as peripheral biomarker. To this aim, serum BACE1 activity was assessed in 115 subjects with LOAD and 151 controls. We found that BACE1 changed across groups (p
Source: AGE - November 19, 2019 Category: Geriatrics Source Type: research

The effects of cardiorespiratory fitness on executive function and prefrontal oxygenation in older adults
AbstractReviews on cardiovascular fitness and cognition in older adults suggest that a higher level of cardiorespiratory fitness may protect the brain against the effects of aging. Although studies reveal positive effects of cardiorespiratory fitness on executive function, more research is needed to clarify the underlying mechanisms of these effects in older adults. The aim of the current study was to assess the association between cardiorespiratory fitness level, cerebral oxygenation, and cognitive performance in older adults (OAs). Seventy-four OAs (68 ± 6.3 years) gave their written, informed consent to participa...
Source: AGE - November 15, 2019 Category: Geriatrics Source Type: research

WormBot, an open-source robotics platform for survival and behavior analysis in C. elegans
AbstractCaenorhabditis elegans is a popular organism for aging research owing to its highly conserved molecular pathways, short lifespan, small size, and extensive genetic and reverse genetic resources. Here we describe the WormBot, an open-source robotic image capture platform capable of conducting 144 parallelC. elegans survival and behavioral phenotyping experiments. The WormBot uses standard 12-well tissue culture plates suitable for solid agar media and is built from commercially available robotics hardware. The WormBot is controlled by a web-based interface allowing control and monitoring of experiments from any inte...
Source: AGE - November 14, 2019 Category: Geriatrics Source Type: research

Methionine restriction delays aging-related urogenital diseases in male Fischer 344 rats
AbstractDietary methionine restriction (MR) has been found to enhance longevity across many species. We hypothesized that MR might enhance longevity in part by delaying or inhibiting age-related disease processes. To this end, male Fischer 344 rats were fed control (CF, 0.86% methionine) or MR (0.17% methionine) diets throughout their life until sacrifice at approximately 30 months of age, and histopathology was performed to identify the incidence and progression of two important aging-related pathologies, namely, chronic progressive nephropathy (CPN) and testicular tumorigenesis. Although kidney pathology was observed in ...
Source: AGE - November 14, 2019 Category: Geriatrics Source Type: research

Transforming growth factor- β promotes basement membrane fibrosis, alters perivascular cerebrospinal fluid distribution, and worsens neurological recovery in the aged brain after stroke
AbstractAging and stroke alter the composition of the basement membrane and reduce the perivascular distribution of cerebrospinal fluid and solutes, which may contribute to poor functional recovery in elderly patients. Following stroke, TGF- β induces astrocyte activation and subsequent glial scar development. This is dysregulated with aging and could lead to chronic, detrimental changes within the basement membrane. We hypothesized that TGF-β induces basement membrane fibrosis after stroke, leading to impaired perivascular CSF distri bution and poor functional recovery in aged animals. We found that CSF entered ...
Source: AGE - November 13, 2019 Category: Geriatrics Source Type: research

The potential role of necroptosis in inflammaging and aging
AbstractAn age-associated increase in chronic, low-grade sterile inflammation termed “inflammaging” is a characteristic feature of mammalian aging that shows a strong association with occurrence of various age-associated diseases. However, the mechanism(s) responsible for inflammaging and its causal role in aging and age-related diseases are not well understood. Age-associated a ccumulation of damage-associated molecular patterns (DAMPs) is an important trigger in inflammation and has been proposed as a potential driver of inflammaging. DAMPs can initiate an inflammatory response by binding to the cell surface ...
Source: AGE - November 13, 2019 Category: Geriatrics Source Type: research

Inflammaging phenotype in rhesus macaques is associated with a decline in epithelial barrier-protective functions and increased pro-inflammatory function in CD161-expressing cells
AbstractThe development of chronic inflammation, called inflammaging, contributes to the pathogenesis of age-related diseases. Although it is known that both B and T lymphocyte compartments of the adaptive immune system deteriorate with advancing age, the impact of aging on immune functions of Th17-type CD161-expressing innate immune cells and their role in inflammaging remain incompletely understood. Here, utilizing the nonhuman primate model of rhesus macaques, we report that a dysregulated Th17-type effector function of CD161+ immune cells is associated with leaky gut and inflammatory phenotype of aging. Higher plasma l...
Source: AGE - November 11, 2019 Category: Geriatrics Source Type: research

The plasma metabolome as a predictor of biological aging in humans
AbstractChronological age is an important predictor of morbidity and mortality; however, it is unable to account for heterogeneity in the decline of physiological function and health with advancing age. Several attempts have been made to instead define a “biological age” using multiple physiological parameters in order to account for variation in the trajectory of human aging; however, these methods require technical expertise and are likely too time-intensive and costly to be implemented into clinical practice. Accordingly, we sought to develop a metabolomic signature of biological aging that could predict cha...
Source: AGE - November 9, 2019 Category: Geriatrics Source Type: research

Polygenic risk score for disability and insights into disability-related molecular mechanisms
AbstractLate life disability is a highly devastating condition affecting 20% or more of persons aged 65 years and older in the USA; it is an important determinant of acute medical and long-term care costs which represent a growing burden on national economies. Disability is a multifactorial trait that contributes substantially to decline of health/wellbeing. Accordingly, gaining insights into the genetics of disability could help in identifying molecular mechanisms of this devastating condition and age-related processes contributing to a large fraction of specific geriatric conditions, concordantly with geroscience. We per...
Source: AGE - November 9, 2019 Category: Geriatrics Source Type: research

Extracellular vesicles from mesenchymal stem cells reduce microglial-mediated neuroinflammation after cortical injury in aged Rhesus monkeys
AbstractCortical injury, such as injuries after stroke or age-related ischemic events, triggers a cascade of degeneration accompanied by inflammatory responses that mediate neurological deficits. Therapeutics that modulate such neuroinflammatory responses in the aging brain have the potential to reduce neurological dysfunction and promote recovery. Extracellular vesicles (EVs) from mesenchymal stem cells (MSCs) are lipid-bound, nanoscale vesicles that can modulate inflammation and enhance recovery in rodent stroke models. We recently assessed the efficacy of intravenous infusions of MSC-EVs (24-h and 14-days post-injury) a...
Source: AGE - November 6, 2019 Category: Geriatrics Source Type: research

Cerebral venous congestion promotes blood-brain barrier disruption and neuroinflammation, impairing cognitive function in mice
AbstractCognitive impairment is one of the most common co-occurring chronic conditions among elderly heart failure patients (incidence: up to ~ 80%); however, the underlying mechanisms are not completely understood. It is hypothesized that in addition to decreased cardiac output, increases in central —and consequentially, cerebral—venous pressure (backward failure) also contribute significantly to the genesis of cognitive impairment. To test this hypothesis and elucidate the specific pathogenic role of venous congestion in the brain, we have established a novel model of increased cerebral ve nous pressure: mice...
Source: AGE - November 5, 2019 Category: Geriatrics Source Type: research

Nanodelivery of phytobioactive compounds for treating aging-associated disorders
AbstractAging population presents a major challenge for many countries in the world and has made the development of efficient means for healthspan extension a priority task for researchers and clinicians worldwide. Anti-aging properties including antioxidant, anti-inflammatory, anti-tumor, and cardioprotective activities have been reported for various phytobioactive compounds (PBCs) including resveratrol, quercetin, curcumin, catechin, etc. However, the therapeutic potential of orally administered PBCs is limited by their poor stability, bioavailability, and solubility in the gastrointestinal tract. Recently, innovative na...
Source: AGE - November 4, 2019 Category: Geriatrics Source Type: research

Treatment with the poly(ADP-ribose) polymerase inhibitor PJ-34 improves cerebromicrovascular endothelial function, neurovascular coupling responses and cognitive performance in aged mice, supporting the NAD+ depletion hypothesis of neurovascular aging
AbstractAdjustment of cerebral blood flow (CBF) to neuronal activity via neurovascular coupling (NVC) plays an important role in the maintenance of healthy cognitive function. Strong evidence demonstrates that age-related cerebromicrovascular endothelial dysfunction and consequential impairment of NVC responses contribute importantly to cognitive decline. Recent studies demonstrate that NAD+ availability decreases with age in the vasculature and that supplemental NAD+ precursors can ameliorate cerebrovascular dysfunction, rescuing NVC responses and improving cognitive performance in aged mice. The mechanisms underlying the...
Source: AGE - November 2, 2019 Category: Geriatrics Source Type: research

Assessment of age-related decline of neurovascular coupling responses by functional near-infrared spectroscopy (fNIRS) in humans
AbstractPreclinical studies provide strong evidence that age-related impairment of neurovascular coupling (NVC) plays a causal role in the pathogenesis of vascular cognitive impairment (VCI). NVC is a critical homeostatic mechanism in the brain, responsible for adjustment of local cerebral blood flow to the energetic needs of the active neuronal tissue. Recent progress in geroscience has led to the identification of critical cellular and molecular mechanisms involved in neurovascular aging, identifying these pathways as targets for intervention. In order to translate the preclinical findings to humans, there is a need to a...
Source: AGE - November 2, 2019 Category: Geriatrics Source Type: research

Age-dependent effects of caloric restriction on mTOR and ubiquitin-proteasome pathways in skeletal muscles
In conclusion, CR-induced reduction of content/ phosphorylation levels of key proteins in mTOR signaling and the UPP occurred in the middle-aged rats but not younger rats. The age-dependent effects of CR on mTOR signaling and the UPP indirectly explained the age-related effects of CR on muscle mass of animals. (Source: AGE)
Source: AGE - November 1, 2019 Category: Geriatrics Source Type: research

The transfer of specific mitochondrial lipids and proteins to lipid droplets contributes to proteostasis upon stress and aging in the eukaryotic model system Saccharomyces cerevisiae
AbstractOriginally Lipid droplets (LDs) were considered as being droplets for lipid storage only. Increasing evidence, however, demonstrates that LDs fulfill a pleiotropy of additional functions. Among them is the modulation of protein as well as lipid homeostasis. Under unfavorable pro-oxidative conditions, proteins can form aggregates which may exceed the overall proteolytic capacity of the proteasome. After stress termination LDs can adjust and support the removal of these aggregates. Additionally, LDs interact with mitochondria, specifically take over certain proteins and thus prevent apoptosis. LDs, which are loaded w...
Source: AGE - November 1, 2019 Category: Geriatrics Source Type: research

Age-related compositional and functional changes in micro-pig gut microbiome
AbstractAge-related changes in human gut microbiota composition have been reported, and such changes might be influenced by the intake of nutrients or diets. To investigate the effects of aging on the gut microbiota independent of nutrient effects, we analyzed the gut microbiomes of 126 micro-pigs at a wide range of ages from newborns to 10 years old. The micro-pigs were reared in a constantly controlled environment. The diversity of the gut microbiome was found to continuously change with age. We also found associations between age and specific members and functions of the gut microbiome. Consistent with previous studies ...
Source: AGE - October 28, 2019 Category: Geriatrics Source Type: research

Nrf2 dysfunction and impaired cellular resilience to oxidative stressors in the aged vasculature: from increased cellular senescence to the pathogenesis of age-related vascular diseases
AbstractAging is associated with increased oxidative stress in vascular endothelial and smooth muscle cells, which contribute to the development of a wide range of diseases affecting the circulatory system in older adults. There is growing evidence that in addition to increased production of reactive oxygen species (ROS), aging critically impairs pathways determining cellular resilience to oxidative stressors. In young organisms, the evolutionarily conserved nuclear factor-erythroid-2-related factor 2 (Nrf2)-mediated antioxidant response pathway maintains cellular reduction-oxidation homeostasis and promotes a youthful cel...
Source: AGE - October 26, 2019 Category: Geriatrics Source Type: research

Age-related alterations of articular cartilage in pituitary adenylate cyclase –activating polypeptide (PACAP) gene–deficient mice
AbstractPituitary adenylate cyclase activating polypeptide (PACAP) is an evolutionarly conserved neuropeptide which is produced by various neuronal and non-neuronal cells, including cartilage and bone cells. PACAP has trophic functions in tissue development, and it also plays a role in cellular and tissue aging. PACAP takes part in the regulation of chondrogenesis, which prevents insufficient cartilage formation caused by oxidative and mechanical stress. PACAP knockout (KO) mice have been shown to display early aging signs affecting several organs. In the present work, we investigated articular cartilage of knee joints in ...
Source: AGE - October 26, 2019 Category: Geriatrics Source Type: research

Fusogenic liposomes effectively deliver resveratrol to the cerebral microcirculation and improve endothelium-dependent neurovascular coupling responses in aged mice
AbstractAdjustment of cerebral blood flow (CBF) to the increased oxygen and nutrient demands of active brain regions via neurovascular coupling (NVC) has an essential role in maintenance of healthy cognitive function. In advanced age, cerebromicrovascular oxidative stress and endothelial dysfunction impair neurovascular coupling, contributing to age-related cognitive decline. Recently we developed a resveratrol (3,4 ′,5-trihydroxystilbene)-containing fusogenic liposome (FL-RSV)-based molecular delivery system that can effectively target cultured cerebromicrovascular endothelial cells, attenuating age-related oxidativ...
Source: AGE - October 25, 2019 Category: Geriatrics Source Type: research

Biomarkers of leaky gut are related to inflammation and reduced physical function in older adults with cardiometabolic disease and mobility limitations
AbstractIntestinal barrier dysfunction is hypothesized to be a contributing determinant of two prominent characteristics of aging: inflammation and decline in physical function. A relationship between microbial translocation (MT), or their biomarkers (lipopolysaccharide binding protein-1 [LBP-1], soluble cluster of differentiation [sCD]-14), and physical function has been reported in healthy older adults, rats, and invertebrates. However, it is not known whether the existence of comorbidities, or clinical interventions intended to reduce comorbidities through weight loss or exercise, alters this connection. We measured inf...
Source: AGE - October 25, 2019 Category: Geriatrics Source Type: research

Astrocyte senescence may drive alterations in GFAP α , CDKN2A p14 ARF , and TAU3 transcript expression and contribute to cognitive decline
In this study, we characterised the senescent cell phenotype in primary human astrocytes in terms of SA- β-Gal staining and SASP secretion, and then assessed splicing factor expression and candidate gene splicing patterns. Finally, we assessed associations between expression of dysregulated isoforms and premature cognitive decline in 197 samples from the InCHIANTI study of ageing, where expression was present in both blood and brain. We demonstrate here that senescent astrocytes secrete a modified SASP characterised by increased IL8, MMP3, MMP10, and TIMP2 but decreased IL10 levels. We identified significant changes i...
Source: AGE - October 25, 2019 Category: Geriatrics Source Type: research

Differential effects of various genetic mouse models of the mechanistic target of rapamycin complex I inhibition on heart failure
AbstractInhibition of mammalian target of rapamycin complex I (mTORC1) by rapamycin improves cardiac function in both aging and heart failure. While the protective mechanisms are not fully understood in mammals, they are presumably mediated through metabolic regulation and suppression of protein translation by reduced phosphorylation of 4EBP1, a target of mTORC1. Using transverse aortic constriction (TAC) and G αq overexpression-induced heart failure models, we examined the effect of cardiac-specific heterozygous deletion (het) of Raptor, a component of mTORC1, and cardiac-specific transgenic overexpression of wild t...
Source: AGE - October 24, 2019 Category: Geriatrics Source Type: research

Individual evaluation of luteinizing hormone in aged C57BL/6  J female mice
This study shows that female mice in regular environmental conditions disp lay stable LH surge timing and amplitude up to 9 months, but at 12 months, the LH surge is delayed with a reduced amplitude, however without overt modification in the estrous cycles. Analysis of individual preovulatory LH secretion and estrous cycle indicates that mice can be followed up to 9 mon ths to investigate the detrimental effects of various parameters on mouse reproductive activity. (Source: AGE)
Source: AGE - October 23, 2019 Category: Geriatrics Source Type: research

Overexpression of catalase targeted to mitochondria improves neurovascular coupling responses in aged mice
AbstractMoment-to-moment adjustment of cerebral blood flow (CBF) to neuronal activity via the homeostatic mechanism known as neurovascular coupling (NVC) has an essential role in maintenance of normal brain function. In advanced age cerebromicrovascular endothelial dysfunction impairs NVC responses, which contribute to age-related cognitive decline. Recently, we have shown that pharmacological treatments that attenuate mitochondrial production of reactive oxygen species (ROS) provide significant neurovascular protection, improving NVC responses in aged mice. Transgenic mice that overexpress human catalase localized to the ...
Source: AGE - October 23, 2019 Category: Geriatrics Source Type: research

Accelerated decline in cognition in a mouse model of increased oxidative stress
This study provides important evidence that increases in oxidative stress alone are sufficient to induce neuroinflammation and cognitive dysfunction that parallels the memory deficits seen in advanced aging and neurodegenerative diseases. (Source: AGE)
Source: AGE - October 22, 2019 Category: Geriatrics Source Type: research

Human geroprotector discovery by targeting the converging subnetworks of aging and age-related diseases
AbstractA key goal of geroscience research is to identify effective interventions to extend human healthspan, the years of healthy life. Currently, majority of the geroprotectors are found by screening compounds in model organisms; whether they will be effective in humans is largely unknown. Here we present a new strategy called ANDRU (agingnetwork baseddrug discovery) to help the discovery of human geroprotectors. It first identifies human aging subnetworks that putatively function at the interface between aging and age-related diseases; it then screens for pharmacological interventions that may “reverse” the ...
Source: AGE - October 21, 2019 Category: Geriatrics Source Type: research

Gastro-intestinal and oral microbiome signatures associated with healthy aging
AbstractThe human oral and gut microbiomes influence health via competition for a distinct niche in the body with pathogens, via metabolic capabilities that increase host digestive capacity and generate compounds engaged in signaling pathways and modulation of immune system functions. Old age alters our metabolic and regenerative capacity. Following recruitment of 65 human subjects in the age range of 70 to 82, we discerned healthy aging (HA) and non-healthy aging (NHA) cohorts discordant in the occurrence of one or more major diseases: (1) cancer, (2) acute or chronic cardiovascular diseases, (3) acute or chronic pulmonar...
Source: AGE - October 16, 2019 Category: Geriatrics Source Type: research

Tamoxifen induction of Cre recombinase does not cause long-lasting or sexually divergent responses in the CNS epigenome or transcriptome: implications for the design of aging studies
AbstractThe systemic delivery of tamoxifen (Tam) to activate inducible CreERT2-loxP transgenic mouse systems is now widely used in neuroscience studies. This critical technological advancement allows temporal control of DNA-cre recombination, avoidance of embryonically lethal phenotypes, and minimization of residual cell labeling encountered in constitutively active drivers. Despite its advantages, the use of Tam has the potential to cause long-lasting, uncharacterized side effects on the transcriptome and epigenome in the CNS, given its mixed estrogen receptor (ER) agonist/antagonist actions. With the welcome focus on inc...
Source: AGE - September 7, 2019 Category: Geriatrics Source Type: research

The enigmatic role of growth hormone in age-related diseases, cognition, and longevity
AbstractGrowth hormone (GH) is secreted by the anterior pituitary gland and regulates various metabolic processes throughout the body. GH and IGF-1 levels are markedly reduced in older humans, leading some to hypothesize GH supplementation could be a viable “anti-aging” therapy. However, there is still much debate over the benefits and risks of GH administration. While an early study of GH administration reported reduced adiposity and lipid levels and increased bone mineral density, subsequent studies failed to show significant benefits. Conversely , other studies found positive effects of GH deficiency includi...
Source: AGE - September 4, 2019 Category: Geriatrics Source Type: research

Correction to: Age-related expression of Neurexin1 and Neuroligin3 is correlated with presynaptic density in the cerebral cortex and hippocampus of male mice
The corresponding author noticed in his published paper that the images (30 weeks, CC, 10, 30 and 50 weeks DG) of fig. 3b are inadvertently duplicated with the images of fig. 3a. Now, these images have been replaced in the corrected panel (Fig. 3b) below. (Source: AGE)
Source: AGE - September 4, 2019 Category: Geriatrics Source Type: research

Anti-inflammatory agent, OKN-007, reverses long-term neuroinflammatory responses in a rat encephalopathy model as assessed by multi-parametric MRI: implications for aging-associated neuroinflammation
AbstractLipopolysaccharide (LPS) –induced encephalopathy induces neuroinflammation. Long-term neuroinflammation is associated with aging and subsequent cognitive impairment (CI). We treated rats that had LPS-induced neuroinflammation with OKN-007, with an anti-inflammatory agent currently considered an anti-cancer investigational new drug in clinical trials for glioblastoma (GBM). Contrast-enhanced magnetic resonance imaging (MRI) (CE-MRI), perfusion MRI, and MR spectroscopy were used as methods to assess long-term (up to 6 weeks post-LPS) alterations in blood-brain barrier (BBB) permeability, microvascularity, ...
Source: AGE - September 2, 2019 Category: Geriatrics Source Type: research

Lipopolysaccharide exposure in a rat sepsis model results in hippocampal amyloid- β plaque and phosphorylated tau deposition and corresponding behavioral deficits
AbstractSepsis is a severe systemic inflammatory response to infection associated with acute and chronic neurocognitive consequences, including an increased risk of later-life dementia. In a lipopolysaccharide-induced rat sepsis model, we have demonstrated neuroinflammation, cortical amyloid-beta plaque deposition, and increased whole brain levels of phosphorylated tau. Hippocampal abnormalities, particularly those of the dentate gyrus, are seen in Alzheimer ’s disease and age-related memory loss. The focus of this study was to determine whether Aβ plaques and phosphorylated tau aggregates occur in the hippocamp...
Source: AGE - August 31, 2019 Category: Geriatrics Source Type: research

Validation of a geropathology grading system for aging mouse studies
This report describes the validation of a grading system, designated as the geropathology grading platform (GGP), which generated a composite lesion score (CLS) for comparison of histological lesion scores in tissues from aging mice. To assess reproducibility of the scoring system, multiple veterinary pathologists independently scored the same slides from the heart, lung, liver, and kidney from two different strains (C57BL/6 and CB6F1) of male mice at 8, 16, 24, and 32  months of age. There was moderate to high agreement between pathologists, particularly when agreement within a 1-point range was considered. CLS for a...
Source: AGE - August 29, 2019 Category: Geriatrics Source Type: research

Validation of a digitally delivered visual paired comparison task: reliability and convergent validity with established cognitive tests
AbstractAlzheimer ’s disease (AD) affects the memory and cognitive function of approximately 5.7 million Americans. Early detection subsequently allows for earlier treatment and improves outcomes. Currently, there exists a validated 30-min eye-tracking cognitive assessment (VPC-30) for predicting AD risk. However, a shorter assessment would improve user experience and improve scalability. Thus, the purposes were to (1) determine convergent validity between the 5-min web camera-based eye-tracking task (VPC-5) and VPC-30, (2) examine the relationship between VPC-5 and gold-standard cognitive tests, and (3) dete rmine t...
Source: AGE - August 29, 2019 Category: Geriatrics Source Type: research

The association of anxio-depressive disorders and depression with motoric cognitive risk syndrome: results from the baseline assessment of the Canadian longitudinal study on aging
AbstractMotoric cognitive risk syndrome (MCR), anxio-depressive disorders (ADD), and depression are associated with cognitive complaint and slow gait speed. The study aims to examine (1) the association of ADD and depression with MCR, and (2) the influence of the type and the severity of ADD and age on this association in older adults. A total of 29,569 participants free from cognitive impairment  with walking speed measure recruited at baseline in the Canadian Longitudinal Study on Aging (CLSA) Comprehensive were selected in this cross-sectional study. They were separated into different sub-groups based on their age ...
Source: AGE - August 28, 2019 Category: Geriatrics Source Type: research