Showing papers in "Rejuvenation Research in 2013"
TL;DR: The multi-component exercise intervention composed by strength, endurance and balance training seems to be the best strategy to improve rate of falls, gait ability, balance, and strength performance in physically frail older adults.
Abstract: The aim of this review was to recommend training strategies that improve the functional capacity in physically frail older adults based on scientific literature, focusing specially in supervised exercise programs that improved muscle strength, fall risk, balance, and gait ability. Scielo, Science Citation Index, MEDLINE, Scopus, Sport Discus, and ScienceDirect databases were searched from 1990 to 2012. Studies must have mentioned the effects of exercise training on at least one of the following four parameters: Incidence of falls, gait, balance, and lower-body strength. Twenty studies that investigated the effects of multi-component exercise training (10), resistance training (6), endurance training (1), and balance training (3) were included in the present revision. Ten trials investigated the effects of exercise on the incidence of falls in elderly with physical frailty. Seven of them have found a fewer falls incidence after physical training when compared with the control group. Eleven trials investigated the effects of exercise intervention on the gait ability. Six of them showed enhancements in the gait ability. Ten trials investigated the effects of exercise intervention on the balance performance and seven of them demonstrated enhanced balance. Thirteen trials investigated the effects of exercise intervention on the muscle strength and nine of them showed increases in the muscle strength. The multi-component exercise intervention composed by strength, endurance and balance training seems to be the best strategy to improve rate of falls, gait ability, balance, and strength performance in physically frail older adults.
608 citations
TL;DR: This review synthesizes behavioral research with neuromolecular mechanisms putatively involved with the low-toxicity cognitive enhancing action of Bacopa monnieri (BM), a medicinal Ayurvedic herb, to integrate molecular neuroscience with behavioral research.
Abstract: This review synthesizes behavioral research with neuromolecular mechanisms putatively involved with the low-toxicity cognitive enhancing action of Bacopa monnieri (BM), a medicinal Ayurvedic herb. BM is traditionally used for various ailments, but is best known as a neural tonic and memory enhancer. Numerous animal and in vitro studies have been conducted, with many evidencing potential medicinal properties. Several randomized, double-blind, placebo-controlled trials have substantiated BM's nootropic utility in humans. There is also evidence for potential attenuation of dementia, Parkinson's disease, and epilepsy. Current evidence suggests BM acts via the following mechanisms—anti-oxidant neuroprotection (via redox and enzyme induction), acetylcholinesterase inhibition and/or choline acetyltransferase activation, β-amyloid reduction, increased cerebral blood flow, and neurotransmitter modulation (acetylcholine [ACh], 5-hydroxytryptamine [5-HT], dopamine [DA]). BM appears to exhibit low toxicity in model organisms and humans; however, long-term studies of toxicity in humans have yet to be conducted. This review will integrate molecular neuroscience with behavioral research.
183 citations
TL;DR: It is reported that in mice the clearance activity of this so-called glymphatic system is strongly stimulated by sleep and is associated with an increase in interstitial volume, possibly by shrinkage of astroglial cells, and this results support a new hypothesis to answer the age-old question of why sleep is necessary.
Abstract: Decline of cognition and increasing risk of neurodegenerative diseases are major problems associated with aging in humans. Of particular importance is how the brain removes potentially toxic biomolecules that accumulate with normal neuronal function. Recently, a biomolecule clearance system using convective flow between the cerebrospinal fluid (CSF) and interstitial fluid (ISF) to remove toxic metabolites in the brain was described. Xie and colleagues now report that in mice the clearance activity of this so-called "glymphatic system" is strongly stimulated by sleep and is associated with an increase in interstitial volume, possibly by shrinkage of astroglial cells. Moreover, anesthesia and attenuation of adrenergic signaling can activate the glymphatic system to clear potentially toxic proteins known to contribute to the pathology of Alzheimer disease (AD) such as beta-amyloid (Abeta). Clearance during sleep is as much as two-fold faster than during waking hours. These results support a new hypothesis to answer the age-old question of why sleep is necessary. Glymphatic dysfunction may pay a hitherto unsuspected role in the pathogenesis of neurodegenerative diseases as well as maintenance of cognition. Furthermore, clinical studies suggest that quality and duration of sleep may be predictive of the onset of AD, and that quality sleep may significantly reduce the risk of AD for apolipoprotein E (ApoE) ɛ4 carriers, who have significantly greater chances of developing AD. Further characterization of the glymphatic system in humans may lead to new therapies and methods of prevention of neurodegenerative diseases. A public health initiative to ensure adequate sleep among middle-aged and older people may prove useful in preventing AD, especially in apolipoprotein E (ApoE) ɛ4 carriers.
136 citations
TL;DR: It is suggested that the frail oldest old with and without MCI have similar functional and neuromuscular outcomes, and the functional outcomes and incidences of falls are associated with muscle mass, strength, and power in the frail elderly population.
Abstract: This study examined the neuromuscular and functional performance differences between frail oldest old with and without mild cognitive impairment (MCI). In addition, the associations betwee...
93 citations
TL;DR: The potential relation between low DHEA levels and well-known age-related diseases, such as sarcopenia, osteoporosis, dementia, sexual disorders, and cardiovascular disease is examined.
Abstract: Dehydroepiandrosterone (DHEA) and its sulfate ester are the most abundant steroids in humans. DHEA levels fall with age in men and women, reaching values sometimes as low as 10%-20% of those encountered in young individuals. This age-related decrease suggests an "adrenopause" phenomenon. Studies point toward several potential roles of DHEA, mainly through its hormonal end products, making this decline clinically relevant. Unfortunately, even if positive effects of DHEA on muscle, bone, cardiovascular disease, and sexual function seem rather robust, extremely few studies are large enough and/or long enough for conclusions regarding its effects on aging. Moreover, because it has been publically presented as a "fountain of youth" equivalent, over-the-counter preparations lacking pharmacokinetic and pharmacodynamic data are widely used worldwide. Conceptually, supplementing a pre-hormone is extremely interesting, because it would permit the human organism to adequately use it throughout long periods, increasing or decreasing end products according to his needs. Nevertheless, data on the safety profile of long-term DHEA supplementation are still lacking. In this article, we examine the potential relation between low DHEA levels and well-known age-related diseases, such as sarcopenia, osteoporosis, dementia, sexual disorders, and cardiovascular disease. We also review risks and benefits of existing protocols of DHEA supplementation.
85 citations
TL;DR: It is concluded that in addition to apparent positive immune remodeling, PattonProtocol-1 may improve markers of metabolic, bone, and cardiovascular health.
Abstract: A short average telomere length is associated with low telomerase activity and certain degenerative diseases. Studies in animals and with human cells confirm a causal mechanism for cell or tissue dysfunction triggered by critically short telomeres, suggesting that telomerase activation may be an approach to health maintenance. Previously, we reported on positive immune remodeling in humans taking a commercial health maintenance program, PattonProtocol-1, composed of TA-65® (a natural product–derived telomerase activator) and other dietary supplements. In over a 5-year period and an estimated 7000 person-years of use, no adverse events or effects have been attributed to TA-65 by physicians licensed to sell the product. Here we report on changes in metabolic markers measured at baseline (n=97–107 subjects) and every 3–6 months (n=27–59 subjects) during the first 12 months of study. Rates of change per year from baseline determined by a multi-level model were −3.72 mg/dL for fasting glucose (p=0.02)...
71 citations
TL;DR: The results suggest that OLE and oleuropein have anti-oxidant protective effects against 6-OHDA-induced PC12 cell damage and suggest their therapeutic potential in the treatment of PD.
Abstract: Parkinson disease (PD) is the most common progressive neurodegenerative disorder characterized by progressive death of midbrain dopaminergic neurons Most neurodegenerative disease treatments are, at present, palliative However, some natural herbal products have been shown to rescue neurons from death and apoptosis in some of neurodegenerative diseases Not only Olea europaea L olive oil, but also the leaves of this plant have been used for medical purposes Olive leaf extract (OLE) is being used by people as a drink across the world and as an integral ingredient in their desire to maintain and improve their health Here, we investigated the effects of OLE and its main phenolic component oleuropein on 6-hydroxydopamine (6-OHDA)-induced toxicity in rat adrenal pheochromocytoma (PC12) cells as an in vitro model of PD Cell damage was induced by 150 μM 6-OHDA The cell survival rate was examined by MTT assay Generation of intra-cellular reactive oxygen species (ROS) was studied using fluorescence
71 citations
TL;DR: It is demonstrated that the administration of GRE reverses behavioral dysfunction and prevents AD-like symptoms in the authors' rat model.
Abstract: The aim of this study was to assess the ability of a traditional Chinese medicinal ginger root extract (GRE) to prevent behavioral dysfunction in the Alzheimer disease (AD) rat model. Rat AD models were established by an operation (OP) in which rats were treated with a one-time intra-cerebroventricuIar injection of amyloid β-protein (Aβ) and continuous gavage of aluminum chloride every day for 4 weeks. GRE was administered intra-gastrically to rats. After 35 days, learning and memory were assessed in all of the rats. Brain sections were processed for immunohistochemistry and Hematoxylin & Eosin (H&E) and Nissl staining. The latency to show significant memory deficits was shorter in the group that received OP with a high dose of GRE (HG)(OP+HG) than in the groups that received OP with a low or moderate dose of GRE (LG, MG)(OP+LG, OP+MG) (p<0.05). The expression of superoxide dismutase (SOD) and catalase (CAT) in the OP+MG and OP+LG groups was up-regulated compared to the OP+HG groups (p<0.05). The...
64 citations
TL;DR: The purpose of this review is to summarize the current understanding of sequence, structure, function, and evolution of GUSB and its lysosomal enzyme targeting.
Abstract: Lysosomal storage diseases occur due to incomplete metabolic degradation of macromolecules by various hydrolytic enzymes in the lysosome. Despite structural differences, most of the lysosomal enzymes share many common features including a lysosomal targeting motif and phosphotransferase recognition sites. β-Glucuronidase (GUSB) is an important lysosomal enzyme involved in the degradation of glucuronate-containing glycosaminoglycan. The deficiency of GUSB causes mucopolysaccharidosis type VII (MPSVII), leading to lysosomal storage in the brain. GUSB is a well-studied protein for its expression, sequence, structure, and function. The purpose of this review is to summarize our current understanding of sequence, structure, function, and evolution of GUSB and its lysosomal enzyme targeting. Enzyme replacement therapy reported for this protein is also discussed.
57 citations
TL;DR: Cataract surgery effectively improves sleep quality and slow gait speed and visual acuity and postoperative increases in the VFQ-25 score were positively correlated with decreases in the Pittsburgh Sleep Quality Index and the PSQI.
Abstract: Background: Gait speed and sleep quality are health indices related to longevity and mortality. In the present study, we measured sleep quality, quality of life, gait speed, and visual acuity before and after cataract surgery to evaluate the efficacy of the procedure on systemic health. Methods: The study was conducted on 155 patients (93 women; average age 74.8 years) undergoing cataract surgery with the implantation of a yellow soft acrylic lens. Patients were evaluated using the Pittsburgh Sleep Quality Index (PSQI) and the National Eye Institute Visual Function Questionnaire 25 (VFQ-25; vision-related quality of life) before and then 2 and 7 months after surgery. Four-meter gait speed was also determined. Results: Of the 155 patients, 68 (43.9%) were classified as poor sleepers (PSQI>5.5) prior to surgery. Significant improvements were noted in sleep 2 months after surgery (p<0.05, paired t-test), but thereafter the improvements were not significant. Prior to surgery, 117 patients (77.0%) wer...
54 citations
TL;DR: The analysis of ATP7B informative SNPs confirms the previous hypothesis about the absence of ATP6B in the significant loci of genome-wide association studies of AD and suggests that transmembrane and adenosine triphosphate (ATP) domains in the ATP7b gene may harbor variants/haplotypes associated with AD risk.
Abstract: Copper dyshomeostasis leading to a labile Cu(2+) not bound to ceruloplasmin ("free" copper) may influence Alzheimer's disease (AD) onset or progression. To investigate this hypothesis, we investigated ATP7B, the gene that controls copper excretion through the bile and concentrations of free copper in systemic circulation. Our study analyzed informative ATP7B single-nucleotide polymorphisms (SNPs) in a case-control population (n=515). In particular, we evaluated the genetic structure of the ATP7B gene using the HapMap database and carried out a genetic association investigation. Linkage disequilibrium (LD) analysis highlighted that our informative SNPs and their LD SNPs covered 96% of the ATP7B gene sequence, distinguishing two "strong LD" blocks. The first LD block contains the gene region encoding for transmembrane and copper-binding, whereas the second LD block encodes for copper-binding domains. The genetic association analysis showed significant results after multiple testing correction for all investigated variants (rs1801243, odds ratio [OR]=1.52, 95% confidence interval [CI]=1.10-2.09, p=0.010; rs2147363, OR=1.58, 95% CI=1.11-2.25, p=0.010; rs1061472, OR=1.73, 95% CI=1.23-2.43, p=0.002; rs732774, OR=2.31, 95% CI=1.41-3.77, p<0.001), indicating that SNPs in transmembrane domains may have a stronger association with AD risk than variants in copper-binding domains. Our study provides novel insights that confirm the role of ATP7B as a potential genetic risk factor for AD. The analysis of ATP7B informative SNPs confirms our previous hypothesis about the absence of ATP7B in the significant loci of genome-wide association studies of AD and the genetic association study suggests that transmembrane and adenosine triphosphate (ATP) domains in the ATP7B gene may harbor variants/haplotypes associated with AD risk.
TL;DR: Results showed that the UV-induced skin damage was significantly improved after HSYA treatment, especially at doses of 100 and 200 μg/mouse, which is possibly related to the anti-oxidative property of HSYA and mediated by promoting endogenous collagen synthesis.
Abstract: Chronic exposure to ultraviolet (UV) irradiation is believed to be the major cause of skin damage that results in premature aging of the skin, so called photoaging, characterized by increases in skin thickness, formation of wrinkles, and loss of skin elasticity. UV induces damage to skin mainly by oxidative stress and collagen degradation. In this study, we examined the photo-protective effect of hydroxysafflor yellow A (HSYA), a major active chemical component isolated from Carthamus tinctorius L., by topical application on the skin of mice. Exposure of the dorsal depilated skin of mice to UV radiation four times a week for 10 weeks induced epidermal hyperplasia, elastin accumulation, collagen degradation, etc. HSYA at the doses of 50, 100, and 200 μg/mouse was topically applied immediately following each UV exposure. The effects of HSYA were evaluated by a series of tests, including macroscopic and histopathological evaluation of skin, pinch test, and redox homeostasis of skin homogenates. Resu...
TL;DR: The data suggest that that presence of specific as yet unidentified microorganisms in the gut linked to diet are required for high TMAO levels and T MAO-mediated CVD progression, and development of novel therapeutic approaches to manipulate gut flora may help treat CVD.
Abstract: The incidence of cardiovascular disease (CVD) increases with age and is associated with some syndromes that exhibit aspects of premature aging, such as progeria. Various factors are thought to contribute to the progression of CVD, including hypertension, hypercholesterolemia, diets rich in saturated and trans fats, etc. Recent reports have uncovered an important connection between diet, the microbiome, and CVD. Dietary carnitine (present predominately in red meat) and lecithin (phosphatidyl choline) are shown to be metabolized by gut microbes to trimethylamine (TMA), which in turn is metabolized by liver flavin monoxygenases (especially FMO3 and FMO1) to form trimethylamine-N-oxide (TMAO). High levels of TMAO in the blood strongly correlate with CVD and associated acute clinical events. Plasma TMAO levels may be an important clinical biomarker for CVD. The data suggest that that presence of specific as yet unidentified microorganisms in the gut linked to diet are required for high TMAO levels and...
TL;DR: The results do not support the idea that isolated phytonutrient anti-oxidants and anti-inflammatories are potential longevity therapeutics, even though consumption of whole fruits and vegetables is associated with enhanced health span and life span.
Abstract: Phytonutrients reportedly extend the life span of Caenorhabditis elegans, Drosophila, and mice. We tested extracts of blueberry, pomegranate, green and black tea, cinnamon, sesame, and French maritime pine bark (Pycnogenol and taxifolin), as well as curcumin, morin, and quercetin for their effects on the life span of mice. While many of these phytonutrients reportedly extend the life span of model organisms, we found no significant effect on the life span of male F1 hybrid mice, even though the dosages used reportedly produce defined therapeutic end points in mice. The compounds were fed beginning at 12 months of age. The control and treatment groups were iso-caloric with respect to one another. A 40% calorically restricted and other groups not reported here did experience life span extension. Body weights were unchanged relative to controls for all but two supplemented groups, indicating most supplements did not change energy absorption or utilization. Tea extracts with morin decreased weight, w...
TL;DR: Experimental evidence is provided that resveratrol confers ability to up-regulate the plasma membrane redox system (PMRS) along with ascorbate free radical reductase, a compensatory system operating in the cell to maintain cellular redox state, and findings suggest a possible role of resver atrol in retardation of age-dependent oxidative stress.
Abstract: Reactive oxygen/nitrogen species (ROS/RNS)–mediated oxidative damage followed by disturbed cellular homeostasis is involved in aging and related consequences. Lipid peroxidation, post-translational modifications of proteins, and an impaired defense system due to increased oxidative stress jeopardize cell fate and functions, resulting in cell senescence. Resveratrol, a natural stilbene, has extensively been reported to elicit a plethora of health-promoting effects. The present study carried out on 97 healthy human subjects (62 males and 35 females) of both sexes provides experimental evidence that resveratrol confers ability to up-regulate the plasma membrane redox system (PMRS) along with ascorbate free radical reductase, a compensatory system operating in the cell to maintain cellular redox state. Furthermore, resveratrol provided significant protection against lipid peroxidation and protein carbonylation and restored the cellular redox homeostasis measured in terms of glutathione (GSH) and sulf...
TL;DR: The study suggests that UI is a marker of frailty and that UI patients should be monitored and, in case, treated in a timely manner to avoid, or to limit, the effects ofFrailty such as malnutrition, falls, and the consequent accumulation of disabilities.
Abstract: Urinary incontinence (UI) is very common in the elderly and has personal and social implications. Many authors have pointed out the necessity to analyze UI in correlation with the overall quality of aging, to better understand this syndrome and define measures for its prevention and treatment. In the present study, we addressed this problem by analyzing the UI correlation with frailty, which has emerged in the last decade as the geriatric syndrome correlated with individual homeostatic capacity and then as the basis of the age-related physical decline. In addition, the monitoring of our sample for a long period allowed us to estimate the prognostic significance of UI by analyzing the correlation between UI and mortality. The analysis was performed in a large sample that included numerous ultra-nonagenarians, a population segment that is still poorly known for UI and other geriatric parameters. We found a strict correlation between UI and frailty, suggesting that UI is correlated to the homeostatic and physiological decline leading to frailty. In addition, we found that UI is an independent mortality risk factor in ultra-nonagenarians, suggesting that the neurological sensitivity needed to be continent is lost very soon when the frailty associated physiological decline begins. On the whole, our study suggests that UI is a marker of frailty and that UI patients should be monitored and, in case, treated in a timely manner to avoid, or to limit, the effects of frailty such as malnutrition, falls, and the consequent accumulation of disabilities.
TL;DR: A significant (p<0.0001) decline in the efflux of L-cysteine in erythrocytes during human aging, and the GSH/GSSG ratio decreases as a function of human age, correlates with the decrease in GSH and the FRAP value.
Abstract: Thiol compounds such as cysteine (Cys) and reduced glutathione (GSH) play an important role in human aging and age-related diseases. In erythrocytes, GSH is synthesized by glutamic acid, cysteine, and glycine, but the rate of GSH synthesis is determined only by the availability of L-cysteine. Cysteine supplementation has been shown to ameliorate several parameters that are known to degenerate during human aging. We have studied L-cysteine efflux in vitro in human erythrocytes as a function of age by suspending cells in solution containing 10 mM L-cysteine for uptake; later cells were re-suspended in phosphate-buffered saline (PBS)–glucose to allow efflux. Change in the free sulfhydryl (–SH) concentration was then measured to calculate the rate of efflux. The GSH/oxidized glutathione (GSSG) ratio was taken as a control to study the oxidation/reduction state of the erythrocyte. The total anti-oxidant potential of plasma was measured in terms of ferric reducing ability of plasma (FRAP) values. We ha...
TL;DR: A review of the therapeutic benefit of melatonin treatment in disorders related to delirium and dementia, including the placebo-controlled randomized clinical trials addressing this topic, is examined.
Abstract: The pineal hormone melatonin plays a major role in circadian sleep-wake rhythm in many mammals, including humans. Patients with acute confusional state or delirium, especially those with underlying cognitive impairment, frequently suffer from sleep disturbances and disturbed circadian rhythm. In this review, an overview is given of delirium and delirium symptoms that correspond with symptoms in dementia, such as sundowning, followed by a presentation of the circadian rhythm disorders in delirium in relation to melatonin deficiency. Finally, this review examines the therapeutic benefit of melatonin treatment in disorders related to delirium and dementia, including the placebo-controlled randomized clinical trials addressing this topic.
TL;DR: This work focuses on apolipoprotein E e2/3/4 polymorphism and ages at onset of cardiovascular diseases (CVD) and cancer in the parental and offspring generations of the Framingham Heart Study participants to gain insights on the role of age and gender across generations in genetic trade-offs.
Abstract: Decades of studies of candidate genes show their complex role in aging-related traits. We focus on apolipoprotein E e2/3/4 polymorphism and ages at onset of cardiovascular diseases (CVD) and cancer in the parental and offspring generations of the Framingham Heart Study participants to gain insights on the role of age and gender across generations in genetic trade-offs. The analyses show that the apolipoprotein E e4 allele carriers live longer lives without cancer than the non-e4 allele carriers in each generation. The role of the e4 allele in onset of CVD is age- and generation-specific, constituting two modes of sexually dimorphic genetic trade-offs. In offspring, the e4 allele confers risk of CVD primarily in women and can protect against cancer primarily in men of the same age. In the parental generation, genetic trade-off is seen in different age groups, with a protective role of the e4 allele against cancer in older men and its detrimental role in CVD in younger women. The puzzling complexity of genetic mechanisms working in different genders, ages, and environments calls for more detail and systemic analyses beyond those adapted in current large-scale genetic association studies.
TL;DR: Investigation of mechanisms will help determine conditions that activate specific genetic variants or profiles and explore to what extent these conditions that shape genetic effects are conserved across human lives and generations.
Abstract: Discovering the genetic origin of aging-related traits could greatly advance strategies aiming to extend health span. The results of genome-wide association studies (GWAS) addressing this problem are controversial, and new genetic concepts have been fostered to advance the progress in the field. A limitation of GWAS and new genetic concepts is that they do not thoroughly address specifics of aging-related traits. Integration of theoretical concepts in genetics and aging research with empirical evidence from different disciplines highlights the conceptual problems in studies of genetic origin of aging-related traits. To address these problems, novel approaches of systemic nature are required. These approaches should adopt the non-deterministic nature of linkage of genes with aging-related traits and, consequently, reinforce research strategies for improving our understanding of mechanisms shaping genetic effects on these traits. Investigation of mechanisms will help determine conditions that activate specific genetic variants or profiles and explore to what extent these conditions that shape genetic effects are conserved across human lives and generations.
TL;DR: Findings provide the first evidence that SMF effectively treats OA by inhibiting cartilage matrix degradation.
Abstract: A Chinese herbal preparation, SiMiaoFang (SMF), has been used clinically for treating arthralgia by virtue of its anti-inflammatory and pain-relieving activities. However, no evidence base links SMF to anti-osteoarthritis (OA), particularly its link to inhibiting cartilage matrix degradation. In this study, we undertook a characterization of anti-OA activity of SMF using an in vivo rat model induced by anterior cruciate ligament transection and medial meniscus resection (ACLT+MMx) together with in vitro studies with chondrocytes for further molecular characterization. ACLT+MMx rats were treated with SMF at doses of 0.63, 1.25, and 2.5 grams/kg per day for 6 weeks. SMF treatments significantly inhibited cartilage matrix degradation, as indicated by increasing proteoglycan and collagen content, particularly type II collagen expression in articular cartilage, decreasing CTX-II (collagen type II degradation marker), and increasing CPII (collagen type II synthesis marker) in circulation. Moreover, SMF...
TL;DR: Oral L-carnitine supplementation for 6 months significantly increased low-density lipoprotein cholesterol (LDL-C), triglycerides, total, free, and acyl carnitine levels, while it decreased alanine transaminase, acyl/free Carnitine ratio, β₂-microglobulin, and skin AGE values.
Abstract: Background and Aims: Advanced glycation end products (AGEs) contribute to cardiovascular disease in patients with hemodialysis (HD). We have recently found that carnitine levels are inversely associated with skin AGE levels in HD patients. We examined whether l-carnitine supplementation reduced skin AGE levels in HD patients with carnitine deficiency. Methods: This was a single-center study. One hundred and two HD patients (total carnitine levels <50 μmol/L) were enrolled and randomized to either oral administration of l-carnitine (900 mg/day) (n=51) or control (n=51). After 6 months, metabolic and inflammatory variables, including serum levels of carnitine, were measured. Skin AGE levels were determined by evaluating skin auto-fluorescence with an AGE-reader. Results: There were no significant differences of clinical variables at baseline between the control and l-carnitine therapy group. Thirty-two patients did not complete the assessment or treatment of the study. Oral l-carnitine supplementat...
TL;DR: It is concluded that diverse anti-oxidant constituents in both plants have a potential influence on skin surface parameters, thus indicating these plants as the future of new anti-aging products.
Abstract: No study has yet determined the anti-wrinkle efficacy of green tea plus lotus in Asian subjects using skin image analysis technique. In this study, the efficacy of two cosmetic active formulations intended for the treatment of facial wrinkles (green tea and lotus extract) has been evaluated in healthy subjects using a non-invasive device, the Visioscan® VC, and software for surface evaluation of living skin (SELS). Thirty-three healthy Asian subjects, all men, were enrolled after consent in a placebo-controlled comparative study with a split face design. One group applied multiple emulsions with green tea. The second group applied multiple emulsions with lotus extract, while a third group applied a multiple emulsion with a combination of both extracts. In all three groups, active formulations were applied to one side of the face and the placebo to the other side, once daily over the 60-day treatment course. Non-invasive measurements were performed at baseline and on days 30 and 60. Interesting an...
TL;DR: Small variations in antioxidant systems homeostasis are associated with relevant modifications of disease risk, and in individuals with analogous TAS values, the presence of the ε4 allele increased the predicted probability of having MTA, further sustain the interaction of oxidative stress and APOE genotype to neurodegeneration.
Abstract: Different factors interact to develop neurodegeneration in patients with dementia and other neurodegenerative disorders. Oxidative stress and the e4 allele of apolipoprotein E (ApoE) are associated with significant alteration in lipid metabolism, in turn connected to a variety of neurodegenerative diseases and aging. Thus, a better understanding of the pathogenetic pathways associated with lipid dyshomeostasis may elucidate the causes of neurodegenerative processes. To address this issue, we evaluated the effects of antioxidant status and APOE genotype on neurodegeneration in patients with dementia of the Alzheimer type (AD), with vascular dementia (VaD), and in elderly healthy controls. Eighty-two AD, 42 VaD patients, and 26 healthy controls were recruited and underwent medial temporal lobe atrophy (MTA) assessment, white matter hyperintensities rating (WMH), serum total antioxidant status assaying (TAS), and APOE genotyping. A logistic regression algorithm applied to our data revealed that a 0....
TL;DR: Among the variables studied, the ability to perform instrumental activities of daily living and using few drugs on a chronic basis at baseline are the best predictors of which oldest-old community-dwelling subjects survive after a 3-year follow-up period.
Abstract: Objective: Few studies have prospectively evaluated the utility of geriatric assessment tools as predictors of mortality in the oldest population. We investigated predictors of death in an oldest-old cohort after 3 years of follow-up. Methods: The Octabaix study is a prospective, community-based study with a follow-up period of 3 years involving 328 subjects aged 85 at baseline. Data were collected on functional and cognitive status, co-morbidity, nutritional and falls risk, quality of life, social risk, and long-term drug prescription. Vital status for the total cohort was evaluated after 3 years of follow-up. Results: Mortality after 3 years was 17.3%. Patients who did not survive had significantly poorer baseline functional status for basic and instrumental activities of daily living (Barthel and Lawton Index), higher co-morbidity (Charlson), higher nutritional risk (Mini Nutritional Assessment), higher risk of falls (Tinetti Gait Scale), poor quality of life (visual analog scale of the Qualit...
TL;DR: It is demonstrated that ALT-711 is capable of cleaving α-diketones more efficiently and likely via a distinct mechanism compared with other N-heterocyclic carbene precursors and may provide insights into the development of next-generation crosslink breakers.
Abstract: Advanced glycation end products (AGEs), a heterogeneous mixture of compounds formed by non-enzymatic chemical reactions between sugars and the nucleophilic residues of proteins, have been implicated in the pathogenesis of a number of diseases. ALT-711 is an N-phenacyl-derived thiazolium carbene developed as a therapeutic agent for cardiovascular diseases that is proposed to function through cleaving preformed AGE-protein crosslinks. However, despite promising results in animal models and clinical trials, its mechanism of action still remains controversial. Herein, we report the first systematic investigations into dicarbonyl cleavage by ALT-711. We demonstrate that it is capable of cleaving α-diketones more efficiently and likely via a distinct mechanism compared with other N-heterocyclic carbene precursors. We also show that ALT-711 reacts rapidly with α-keto aldehydes to form cyclic diol products, and it can efficiently scavenge methylglyoxal under physiological conditions to protect Escherichia coli from lethal concentrations of this reactive α-keto aldehyde. This work suggests ALT-711 may be especially suited for α-dicarbonyl clearance in vivo and supports a mode of action similar to that originally proposed. To this end, our findings may provide insights into the development of next-generation crosslink breakers.
TL;DR: Interventions that inhibit nitration and restore TrxR activity might be a therapy for attenuating enhanced MI/R injury in aging heart.
Abstract: The age-related loss of anti-oxidant defense reduces recovery from myocardial ischemia/reperfusion injury (MI/R) in aged people. Our previous data showed that inactivation of thioredoxin (Trx) was involved in enhanced aging MI/R injury. Thioredoxin reductase (TrxR), the enzyme known to regulate Trx, is less efficient with age. The aim of the current study was to determine why TrxR activity was reduced and whether reduced TrxR activity contributed to enhanced aging MI/R injury. Both Trx and TrxR activity were decreased in the aging heart, and this difference was further amplified after MI/R. However, MI/R injury did not change TrxR expression between young and aging rats. Increased nitrogen oxide (NOx) but decreased nitric oxide (NO) bioavailability (decreased phosphorylated vasodilator-stimulated phosphoprotein) was observed in aging hearts. Peroxynitrite (ONOO⁻) was increased in aging hearts and was further amplified after MI/R. TrxR nitration in young and aging hearts was detected by immunoprecipitation (anti-nitrotyrosine) followed by immunoblotting (anti-TrxR). Compared with young hearts, TrxR nitration was increased in the aging hearts, and this was further intensified after MI/R. The ONOO⁻ decomposition catalyst (FeTMPyp) reduced TrxR nitration and increased TrxR and Trx activity. More importantly, FeTMPyp attenuated the MI/R injury in aging hearts as evidenced by decreased caspase-3 and malondialdehyde (MDA) concentration and increased cardiac function. Increased ONOO⁻ nitrated TrxR in the aging heart as a post-translational modification, which may be related to the enhanced MI/R injury of aging rats. Interventions that inhibit nitration and restore TrxR activity might be a therapy for attenuating enhanced MI/R injury in aging heart.
TL;DR: Although observations in mouse models of AD might not necessarily extrapolate to humans, bexarotene is a very interesting potential drug against AD; phase I and II clinical trials are under way.
Abstract: Despite decades of research, there is no cure for Alzheimer disease (AD), and current pharmacological treatments only partially mask the symptoms while the disease progresses within the brain. AD is associated with impaired clearance of β-amyloid (Aβ) from the brain, a process facilitated by apolipoprotein E (ApoE), whose expression is transcriptionally regulated by the ligand-activated nuclear receptors peroxisome proliferator-activated receptor-γ (PPARγ) and liver X receptor (LXR), in conjunction with retinoid X receptor (RXR). A very interesting study performed by G.E. Landreth's group in three murine models of AD has shown that the RXR agonist bexarotene (Targretin), Food and Drug Administration (FDA) approved and used since 1999 for the treatment of cutaneous T cell lymphoma, promotes a fast ApoE-dependent clearance of soluble Aβ peptides from the brain, reduces Aβ plaques, and stimulates the reversal of cognitive, social, and olfactory deficits. Four independent studies tried to replicate these observations; the clearance of soluble Aβ peptides and the reversal of cognitive deficits were replicated in two studies, but all of the studies failed to replicate the reduction of Aβ plaques. In a second report, G.E. Landreth's group formulates some hypotheses to explain these discrepancies. Although observations in mouse models of AD might not necessarily extrapolate to humans, bexarotene is a very interesting potential drug against AD; phase I and II clinical trials are under way.
TL;DR: Results show that oxidative stress and anti-oxidant enzyme activities in trophocytes and fat cells increase with advancing age in queens and suggest that an increase in oxidative Stress and a consequent increase in stress defense mechanisms are associated with the longevity of queen honeybees.
Abstract: Trophocytes and fat cells of queen honeybees have been used for delayed cellular senescence studies, but their oxidative stress and anti-oxidant enzyme activities with advancing age are unknown In this study, we assayed reactive oxygen species (ROS) and anti-oxidant enzymes in the trophocytes and fat cells of young and old queens Young queens had lower ROS levels, lower superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, and higher thioredoxin reductase (TR) activity compared to old queens These results show that oxidative stress and anti-oxidant enzyme activities in trophocytes and fat cells increase with advancing age in queens and suggest that an increase in oxidative stress and a consequent increase in stress defense mechanisms are associated with the longevity of queen honeybees
TL;DR: It is believed that a validated predictive model including age, ECOG-PS, and type of chemotherapy (platinum- vs. non-platinum containing regimen) would enable clinicians to target thromboprophylaxis to those patients considered to be at greatest risk.
Abstract: Data on the relationship between aging, chemotherapy, and risk for venous thromboembolism (VTE) are controversial. We sought to evaluate the risk of chemotherapy-associated VTE in young to middle-aged (YMA) and elderly cancer patients and to analyze the VTE-free survival time in both groups. Patients with histologically confirmed diagnosis of solid malignancy receiving any type of systemic chemotherapy, no clinical diagnosis of VTE before chemotherapy initiation, and Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2 were enrolled in this study. Of the 486 consecutive patients included in the study, 380 (78%) were classified as YMA (≤70 years of age) and 106 (22%) as elderly (>70 years of age). At a median follow-up of 1 year, the incidence of VTE events was almost two-fold greater in elderly than in YMA (11% vs. 6%). Age (≤70 years vs. >70 years (hazard ratio [HR], 2.42; 95% confidence interval [CI] 1.15-5.06; p=0.020), ECOG-PS (HR, 6.54; 95% CI 3.10-13.8; p<0.0001), and platinum-based chemotherapy (HR, 2.46; 95% CI 1.06-5.69; p=0.035) were independent risk factors for VTE. In the elderly subset, a trend toward an increased risk of VTE in patients receiving a platinum-based chemotherapy when compared with a non-platinum-containing regimen was observed (15% vs. 9.1%). The Kaplan-Meier analysis showed that elderly patients had a significantly shorter VTE-free survival time compared with younger cancer patients (log-rank test=2.0; p=0.045). Our study reports an increase incidence of VTE in elderly cancer patients treated with chemotherapy compared with the younger group, suggesting that aging is one of the most important risk factors for VTE. On the basis of the results of this study, we believe that a validated predictive model including age, ECOG-PS, and type of chemotherapy (platinum- vs. non-platinum containing regimen) would enable clinicians to target thromboprophylaxis to those patients considered to be at greatest risk.