Rhabdomyolysis is a syndrome caused by injury to skeletal muscle. There is limited data of rhabdomyolysis in the elderly. The objective of this study is to investigate demographic data, etiologies, laboratory values, prognostic factors, and mortality of rhabdomyolysis in the geriatric population. A 4-years retrospective chart review study was conducted. Our inclusion criteria were age above 65 years and creatinine kinase level excess five times of normal upper limit. Among 167 patients, 47.3% were male. The median age at diagnosis was 80.11 (66-101) years. The duration of follow up in the study ranged from 0 to 48 months. Fall (with or without immobilization) was the most frequent cause of rhabdomyolysis in 56.9%. The mean baseline glomerular filtration rate (GFR), GFR at diagnosis, and peak decline in GFR was 76.94, 48.96, and 54.41 cc/min respectively. The mean CK at diagnosis and peak CK was 5097.22 and 6320.07. There were 45 deaths (21%) over the span of 4 years. Multivariate analysis demonstrated that number of medications pre-admission (Meds No.), peak decline in GFR, and acute kidney injury (AKI) are independent predictors for overall survival for rhabdomyolysis in the elderly. To our knowledge, this is the first epidemiological study of rhabdomyolysis in the elderly. Falls (with and without immobilization) were the most common etiology. Meds No. (>8), peak decline in GFR (<30 cc/min), and evidence of AKI are associated with shorter overall survival and can serve as potential independent prognostic markers for rhabdomyolysis in elderly patients.
Parkinson’s disease (PD) patients with 10 years or more survival (PD-10) are not well characterized. The aim of this study was to evaluate the main issues facing PD-10 patients and identify factors that independently contributed to quality of life (QoL).
A group of 121 PD-10 patients recruited from outpatient clinics participated in this cross-sectional study. Data on demographic and clinical factors were collected. Multiple linear regression analyses were conducted to identify determinants of poor QoL.
The entire PD-10 patients had disease duration ranging from 10 to 23 years, with 84.2% of the total cohort skewed to between 10 and 15 years’ duration. The PD-10 patients had great frequency of left-sided onset, increased motor and non-motor symptoms as well as inferior QoL. The more advanced stage of disease in PD-10 patients was associated with motor phenotype, freezing of gait, higher UPDRS sub-scores and levodopa equivalent dose, less balanced confidence, fatigue, anxiety, depression, reduced quality of life and worse Timed Up & Go performance. Self-reported mood symptoms, decreased balance confidence and reduced daily activities were the three factors most closely associated with poorer QoL, but excessive daytime sleepiness and long disease duration additionally contributed to the explanatory power.
This is the first report to investigate the clinical characteristics of Chinese PD-10 patients. Our study may elucidate an important clue for understanding PD-10 patients in clinical practice and identifying patients with PD at risk for reduced QoL.
TCF7L2 is located at one of the most strongly associated type 2 diabetes loci reported to date. We previously reported that the most abundant member of a specific protein complex to bind across the presumed causal variant at this locus, rs7903146, was poly [ADP-ribose] polymerase type 1 (PARP-1). We analyzed the impact of PARP-1 inhibition on C. elegans health in the setting of hyperglycemia and on glucose-stimulated GLP-1 secretion in human intestinal cells. Given that high glucose concentrations progressively shorten the lifespan of C. elegans, in part by impacting key well-conserved insulin-modulated signaling pathways, we investigated the effect of PARP-1 inhibition with Olaparib on the lifespan of C. elegans nematodes under varying hyperglycemic conditions. Subsequently, we investigated whether Olaparib treatment had any effect on glucose-stimulated GLP-1 secretion in the human NCI-H716 intestinal cell line, a model system for the investigation of enteroendocrine function. Treatment with 100uM Olaparib in nematodes exposed to high concentrations of glucose led to significant lifespan rescue. The beneficial lifespan effect of Olaparib appeared to require both PARP-1 and TCF7L2, since treatment had no effect in hyperglycemic conditions in knock-out worm strains for either of these homologs. Further investigation using the NCI-H716 cells revealed that Olaparib significantly enhanced secretion of the incretin, GLP-1, plus the gene expression of TCF7L2, GCG and PC1. These data from studies in both C. elegans and a human cell line suggest that PARP-1 inhibition offers a novel therapeutic avenue to treat type 2 diabetes.
Experimental cardiac arrest (CA) in aging research is infrequently studied in part due to the limitation of animal models. We aimed to develop an easily performed mouse CA model to meet this need. A standard mouse KCl-induced CA model using chest compressions and intravenous epinephrine for resuscitation was modified by blood withdrawal prior to CA onset, so as to decrease the requisite KCl dose to induce CA by decreasing the circulating blood volume. The modification was then compared to the standard model in young adult mice subjected to 8 min CA. 22-month old mice were then subjected to 8 min CA, resuscitated, and compared to young adult mice. Post-CA functional recovery was evaluated by measuring spontaneous locomotor activity pre-injury, and on post-CA days 1, 2, and 3. Neurological score and brain histology were examined on day 3. Brain elF2α phosphorylation levels were measured at 1 h to verify tissue stress. Compared to the standard model, the modification decreased cardiopulmonary resuscitation duration and increased 3-day survival in young mice. For aged mice, survival was 100 % at 24 h and 54% at 72 h. Neurological deficit was present 3 days post-CA, although more severe versus young mice. Mild neuronal necrosis was present in the cortex and hippocampus. The modified model markedly induced elF2α phosphorylation in both age groups. This modified procedure makes the CA model feasible in aged mice and provides a practical platform for understanding injury mechanisms and developing therapeutics for elderly patients.
Evidence indicated that inflammatory response and some pattern-recognition receptors play important roles in the occurrence and progression of osteoarthritis. This study is conducted to evaluate the role of RIG-I and its adaptor protein MAVS in the pathogenesis of osteoarthritis. Four SNPs in RIG-I gene and four in MAVS gene were genotyped in 1056 Chinese Han population. We also overexpressed MAVS in murine chondrogenic ATDC5 cells and analyzed the cell viability and apoptosis. Rs11795343 (P-allele: 0.063394) in RIG-I, rs17857295 (P-allele: 0.073518) and rs7262903 (P-allele: 0.054052, P-genotype: 0.067930) in MAVS were marginally associated with OA. Rs7269320 (P-allele: 0.014783, P-genotype: 0.03272) in MAVS was significant associated with OA. Further analyses in different genders indicated that rs7262903 (P-allele: 0.017256, P-genotype: 0.045683) and rs7269320 (P-allele: 0.013073, P-genotype: 0.038881) are significantly associated with OA in female group. Haplotype analyses indicated G-C-G (χ2: 4.328, P-value: 0.037503) in rs10813821-rs11795343-rs659527 block of RIG-I, G-C-A-T (χ2: 4.056, P-value: 0.044028) and G-C-C-C (χ2: 14.295, P-value: 0.000158) in rs17857295-rs2326369-rs7262903-rs7269320 block of MAVS were significantly associated with OA. Furthermore, forced expression of MAVS could suppress the viability and promote the apoptosis of ATDC5 chondrogenic cells. In conclusion, this study indicated that RIG-I and MAVS are probably associated with OA in the females of Chinese Han population. And MAVS might be a novel risk factor for OA which may involve in growth of chondrocytes and cartilage homeostasis.
Trefoil factor 3 (TFF3), cholinesterase activity (ChE activity) and homocysteine (Hcy) play critical roles in modulating recognition, learning and memory in neurodegenerative diseases, such as Parkinson’s disease dementia (PDD) and vascular parkinsonism with dementia (VPD). However, whether they can be used as reliable predictors to evaluate the severity and progression of PDD and VPD remains largely unknown. Methods: We performed a cross-sectional study that included 92 patients with PDD, 82 patients with VPD and 80 healthy controls. Serum levels of TFF3, ChE activity and Hcy were measured. Several scales were used to rate the severity of PDD and VPD. Receivers operating characteristic (ROC) curves were applied to map the diagnostic accuracy of PDD and VPD patients compared to healthy subjects. Results: Compared with healthy subjects, the serum levels of TFF3 and ChE activity were lower, while Hcy was higher in the PDD and VPD patients. These findings were especially prominent in male patients. The three biomarkers displayed differences between PDD and VPD sub-groups based on genders and UPDRS (III) scores’ distribution. Interestingly, these increased serum Hcy levels were significantly and inversely correlated with decreased TFF3/ChE activity levels. There were significant correlations between TFF3/ChE activity/Hcy levels and PDD/VPD severities, including motor dysfunction, declining cognition and mood/gastrointestinal symptoms. Additionally, ROC curves for the combination of TFF3, ChE activity and Hcy showed potential diagnostic value in discriminating PDD and VPD patients from healthy controls. Conclusions: Our findings suggest that serum TFF3, ChE activity and Hcy levels may underlie the pathophysiological mechanisms of PDD and VPD. As the race to find biomarkers or predictors for these diseases intensifies, a better understanding of the roles of TFF3, ChE activity and Hcy may yield insights into the pathogenesis of PDD and VPD.
Diabetes Mellitus is a common disorder, with increasing risk of cardiac arrhythmias. Studies have shown that altered connexin expression and gap junction remodeling under hyperglycemia contribute to the high prevalence of cardiac arrhythmias and even sudden death. Connexin 43 (Cx43), a major protein that assembles to form cardiac gap junctions, has been found to be downregulated under high glucose conditions, along with inhibition of gap junctional intercellular communication (GJIC). While, apelin, a beneficial adipokine, increases Cx43 protein expression in mouse and human embryonic stem cells during cardiac differentiation. However, it remains unknown whether apelin influences GJIC capacity in cardiomyocytes. Here, using Western blotting and dye transfer assays, we found that Cx43 protein expression was reduced and GJIC was impaired after treatment with high glucose, which, however, could be abrogated after apelin treatment for 48 h. We also found that apelin increased Cx43 expression under normal glucose. Real-time PCR showed that the Cx43 mRNA was not significantly affected under high glucose conditions in the presence of apelin or high glucose and apelin. High glucose decreased the phosphorylation of AMPKα; however, apelin activated AMPKα. Interestingly, we found that Cx43 expression was increased after treatment with AICAR, an activator of AMPK signaling. AMPKα inhibition mediated with transfection of siRNA-AMPKα1 and siRNA-AMPKα2 abolished the protective effect of apelin on Cx43 expression. Our data suggest that apelin attenuates high glucose-induced Cx43 downregulation and improves the loss of functional gap junctions partly through the AMPK pathway.
In Lebanon, data stemming from national cross-sectional surveys indicated significant increasing trends in the prevalence of cardiovascular diseases and associated behavioral and age-related risk factors. To our knowledge, no data are available on relative telomere length (RTL) as a potential biomarker for age-related diseases in a Lebanese population. The aim of this study was to evaluate whether there is an association between RTL and demographic characteristics, lifestyle habits and diseases in the Lebanese. This was a cross-sectional study of 497 Lebanese subjects. Peripheral blood RTL was measured by amplifying telomere and single copy gene using real-time PCR. Mean ± SD RTL was 1.42 ± 0.83, and it was categorized into 3 tertiles. Older age (P=0.002) and wider waist circumference (WC) (P=0.001) were statistically significantly associated with shorter RTL. Multinomial logistic regression showed that subjects who had some level of sleeping difficulty had a statistically significantly shorter RTL when compared to those with no sleeping difficulties at all [OR (95% CI): 2.01 (1.11-3.62) in the first RTL tertile]. Importantly, statistically significantly shorter RTL was found with every additional 10 cm of WC [OR (95% CI): 1.30 (1.11-1.52) for first RTL tertile]. In addition, and after performing the multivariate logistic regression and adjusting for “predictors” of RTL, the odds of having hypertension or being treated for hypertension were higher in patients who had shorter RTL: OR (95% CI): 2.45 (1.36-4.44) and 2.28 (1.22-4.26) in the first RTL tertiles respectively with a similar trend, though not statistically significant, in the second RTL tertiles. This is the first study in Lebanon to show an association between age, central obesity, poor sleep and hypertension and RTL. It is hoped that telomere length measurement be potentially used as a biomarker for biological age and age-related diseases and progression in the Lebanese.
Increased life expectancy is associated with a high prevalence of chronic, non-communicable diseases including cognitive decline and dementia. The purpose of this study was to evaluate the prevalence of cognitive impairment using three cognitive abilities (verbal fluency, numeracy and perceived memory) and their association with cardiovascular risk factors in seniors across Europe. Data from participants in wave 4 of the SHARE (Survey of Health, Ageing, and Retirement in Europe) database was used. Cognitive performance in perceived memory, verbal fluency and numeracy was evaluated using simple tests and a memory complaints questionnaire. Clinical and sociodemographic variables were also studied for potential associations. Standardised prevalence rates of cognitive impairment based on age and gender were calculated by country. The prevalence of cognitive impairment was 28.02% for perceived memory, 27.89% for verbal fluency and 20.75% for numeracy throughout the 16 evaluated countries. Years of education, being a current or former smoker, number of chronic diseases, diabetes or hyperglycemia, heart attack and stroke were all independent variables associated with impairment in the three studied cognitive abilities. We also found independent associations between physical inactivity and verbal fluency and numeracy impairment, as well as hypertension and perceived memory impairment. Lower performance in the evaluated cognitive abilities and higher memory complaints are highly prevalent, have a heterogeneous distribution across Europe, and are associated with multiple factors, most of which are potentially preventable or treatable, especially cardiovascular risk factors.
The objective of this study was to explore the causes of death in Chinese patients with multiple system atrophy (MSA) as well as differences in the cause of death according to sex, subtype, disease onset, and whether the disease was accompanied by nocturnal stridor. A total of 131 MSA patients were enrolled and followed up once every year until their deaths. Clinical information was collected by neurologists, and the cause of death of the MSA patients was obtained from the patients’ relatives or caregivers. The current study included 62 MSA with predominant parkinsonism (MSA-P) and 69 MSA with predominant cerebellar ataxia (MSA-C) patients. Median survival time from disease onset to death of the MSA patients was 5.59 years. The most common cause of death was respiratory infection (65.6%). The second most common cause of death was sudden death (14.5%). Other causes included nutritional disorder due to dysphagia (9.2%), urinary tract infection (3.1%), suicide (2.3%), choking (1.5%), cerebrovascular accident (1.5%), myocardial infarction (1.5%), and lymphoma (0.8%). We found that sudden death was more likely to occur in patients with nocturnal stridor than in those without (P<0.001). There were no significant differences in the cause of death according to subtype, sex, or onset symptoms (autonomic failure or motor symptoms). Sudden death is a relatively common cause of death in MSA patients, second only to respiratory infection, especially in patients with nocturnal stridor. The information provided by our study may help to provide better medical care to MSA patients.
Brain aging is associated with changes of various metabolic pathways. Copper is required for brain development and function, but little is known about changes in copper metabolism during brain aging. The objective of this study was to investigate alteration of copper fluxes in the aging mouse brain with positron emission tomography/computed tomography using 64CuCl2 as a radiotracer (64CuCl2-PET/CT). A longitudinal study was conducted in C57BL/6 mice (n = 5) to measure age-dependent brain and whole-body changes of 64Cu radioactivity using PET/CT after oral administration of 64CuCl2 as a radiotracer. Cerebral 64Cu uptake at 13 months of age (0.17 ± 0.05 %ID/g) was higher than the cerebral 64Cu uptake at 5 months of age (0.11 ± 0.06 %ID/g, p < 0.001), followed by decrease to (0.14 ± 0.04 %ID/g, p = 0.02) at 26 months of age. In contrast, cerebral 18F-FDG uptake was highest at 5 months of age (7.8 ± 1.2 %ID/g) and decreased to similar values at 12 (5.2 ± 1.1 %ID/g, p < 0.001) and 22 (5.6 ± 1.1 %ID/g, p < 0.001) months of age. The findings demonstrated alteration of copper fluxes associated with brain aging and the time course of brain changes in copper fluxes differed from changes in brain glucose metabolism across time, suggesting independent underlying physiological processes. Hence, age-dependent changes of cerebral copper fluxes might represent a novel metabolic biomarker for assessment of human brain aging process with PET/CT using 64CuCl2 as a radiotracer.
Muscle atrophy is an unfortunate effect of aging and many diseases and can compromise physical function and impair vital metabolic processes. Low levels of muscular fitness together with insufficient dietary intake are major risk factors for illness and mortality from all causes. Ultimately, muscle wasting contributes significantly to weakness, disability, increased hospitalization, immobility, and loss of independence. However, the extent of muscle wasting differs greatly between individuals due to differences in the aging process per se as well as physical activity levels. Interventions for sarcopenia include exercise and nutrition because both have a positive impact on protein anabolism but also enhance other aspects that contribute to well-being in sarcopenic older adults, such as physical function, quality of life, and anti-inflammatory state. The process of aging is accompanied by chronic immune activation, and sarcopenia may represent a consequence of a counter-regulatory strategy of the immune system. Thereby, the kynurenine pathway is induced, and elevation in the ratio of kynurenine to tryptophan concentrations, which estimates the tryptophan breakdown rate, is often linked with inflammatory conditions and neuropsychiatric symptoms. A combined exercise program consisting of both resistance-type and endurance-type exercise may best help to ameliorate the loss of skeletal muscle mass and function, to prevent muscle aging comorbidities, and to improve physical performance and quality of life. In addition, the use of dietary protein supplementation can further augment protein anabolism but can also contribute to a more active lifestyle, thereby supporting well-being and active aging in the older population.
Presbycusis (age-related hearing loss) is the most universal sensory degenerative disease in elderly people caused by the degeneration of cochlear cells. Non-coding microRNAs (miRNAs) play a fundamental role in gene regulation in almost every multicellular organism, and control the aging processes. It has been identified that various miRNAs are up- or down-regulated during mammalian aging processes in tissue-specific manners. Most miRNAs bind to specific sites on their target messenger-RNAs (mRNAs) and decrease their expression. Germline mutation may lead to dysregulation of potential miRNAs expression, causing progressive hair cell degeneration and age-related hearing loss. Therapeutic innovations could emerge from a better understanding of diverse function of miRNAs in presbycusis. This review summarizes the relationship between miRNAs and presbycusis, and presents novel miRNAs-targeted strategies against presbycusis.
NSAIDs, non-steroidal anti-inflammatory drugs, are one of the most commonly prescribed pain medications. It is a highly effective drug class for pain and inflammation; however, NSAIDs are known for multiple adverse effects, including gastrointestinal bleeding, cardiovascular side effects, and NSAID induced nephrotoxicity. As our society ages, it is crucial to have comprehensive knowledge of this class of medication in the elderly population. Therefore, we reviewed the pharmacodynamics and pharmacokinetics, current guidelines for NSAIDs use, adverse effect profile, and drug interaction of NSAIDs and commonly used medications in the elderly.
There has been increasing interest and research into sarcopenia in community-dwelling older adults since the European Working Group on Sarcopenia in Older People (EWGSOP) agreed a consensus definition in 2010. Sarcopenia has been defined as loss of muscle mass with loss of muscle function (strength or physical performance), with measurements two Standard Deviations (SDs) below the mean of a young reference population. This definition does not necessitate longitudinal measurements, or the absence of acute illness and diagnosis can be made from single measurements. We hypothesise that hospitalisation, due to a combination of acute inflammatory burden and muscle disuse, leads to an acute decline in muscle mass and function and may lead to some individuals meeting criteria for sarcopenia, acutely, based on the EWGSOP definition. This may be partially recoverable or may lead to increased risk of developing sarcopenia long-term. We have denoted the term “acute sarcopenia” to refer to acute loss of muscle mass and function associated with hospitalisation. This review discusses some of the current available research in this context and also identifies some of the knowledge gaps and potential areas for future research.
Chronic remote ischemic conditioning (RIC), particularly long-term repeated RIC, has been applied in clinical trials with the expectation that it could play its protective roles for protracted periods. In sports medicine, chronic RIC has also been demonstrated to improve exercise performance, akin to improvements seen with regular exercise training. Therefore, chronic RIC may mimic regular exercise, and they may have similar underlying mechanisms. In this study, we explored the common underlying mechanisms of chronic RIC and physical exercise in protecting multiple organs and benefiting various populations, the advantages of chronic RIC, and the challenges for its popularization. Intriguingly, several underlying mechanisms of RIC and exercise have been shown to overlap. These include the production of many autacoids, enhanced ability for antioxidant activity, modulating immune and inflammatory responses. Therefore, it appears that chronic RIC, just like regular exercise, has beneficial effects in unhealthy, sub-healthy and healthy individuals. Compared with regular exercise, chronic RIC has several advantages, which may provide novel insights into the area of exercise and health. Chronic RIC may enrich the modes of exercise, and benefit individuals with severe diseases. Also, the disabled, and sub-healthy individuals are likely to benefit from chronic RIC either as an alternative to exercise or an adjunct to pharmacological or non-pharmacological therapy.