Cause Of Frailty Research Articles

Research progress of gut microbiota and frailty syndrome.

Frailty is a clinical syndrome caused by homeostasis imbalance. It is characterized by marked vulnerability to endogenous or exogenous stressors, reduced self-care ability, and increased mortality risk. This aging-related syndrome is common in individuals older than 65 years and carries an increased risk for poor health outcomes. These include falls, incident disability, incapacity, and mortality. In addition, it can result in a poor prognosis for other comorbidities. With the aging population, frailty increases the burden of adverse health outcomes. Studies on frailty are at their infancy. In addition, there is a lack of thorough understanding of its pathogenesis. Several studies have suggested that frailty is caused by chronic inflammation due to enhanced intestinal permeability following gut microbiota imbalance as well as pathogen-related antibodies entering the circulation system. These result in musculoskeletal system disorders and neurodegenerative diseases. However, this assumption has not been validated in large cohort-based studies. Several studies have suggested that inflammation is not the only cause of frailty. Hence, further studies are necessary to extend our understanding of its pathogenesis. This review summarizes the research findings in the field and expands on the possible role of the gut microbiota in frailty syndrome.

Physical Frailty/Sarcopenia as a Key Predisposing Factor to Coronavirus Disease 2019 (COVID-19) and Its Complications in Older Adults

The tremendously rising numbers of aged populations are associated with a heightened risk for motor and functional declines. Sarcopenia is an active age-related process that involves progressive losses of skeletal muscle mass, muscle strength, and muscle function. Muscle failure is a major cause of frailty, disability, falls, hospitalization, dependency, institutionalization, and low quality of life in older seniors. Therefore, sarcopenia considerably heightens the annual cost of care worldwide. This narrative review elaborates on sarcopenia as a deleterious condition in old age while spotting the light on its association with the coronavirus disease 2019 (COVID-19). It discusses its pathophysiology and the most possible options for preventing and treating sarcopenia. The literature shows that the dynamic of sarcopenia is complex, involving multifaceted physiological alterations relevant to aging, unhealthy behaviors (e.g., undernutrition or inadequate dietary intake and physical inactivity/immobility or sedentary lifestyle), and multiple pathogenic conditions such as metabolic, inflammatory, and endocrinal disorders. Frail individuals express nutritional deficiencies, immune deficit, oxidative stress, metabolic alterations, gut microbial alterations, neurological insult, etc. Such physiological dysfunctions are closely linked to increased vulnerability to COVID-19 among older adults and people with non-communicable diseases such as diabetes mellitus, cardiovascular disorders, and obesity. Available studies report higher occurrence of severe COVID-19 and COVID-19-related complications (ICU admission, mechanical ventilation, and in-hospital mortality) among frail compared with non-frail and prefrail individuals. Effective pharmacological treatments of sarcopenia are not currently available. However, physical activity and nutritional interventions (e.g., fast digestive proteins, vitamin D, and natural products such as bee products) may prevent the development of sarcopenia in early stages of the disease or limit disease progress. Such interventions may also lower vulnerability to COVID-19.

Enhanced small neutral but not branched chain amino acid transport after epigenetic sodium coupled neutral amino acid transporter-2 (SNAT2) cDNA expression in myoblasts.

BackgroundSkeletal muscle mass and function are partly maintained by the supply of amino acids, altered amino acid transport is an important cause of frailty that can lead to decreased independence with increasing age and slow trauma recovery. The system‐A sodium coupled neutral amino acid transporter (SNAT)‐2 coded by gene family SLC38A2 generates a 506 amino acid 56 kDa protein that is an important transporter of amino acids in skeletal muscle. Ageing is associated with a decrease in expression of SNAT2 transporters.MethodsIn this study, we used the C2C12 cell line, using myoblast cells and cells differentiated into myotubes. We investigated if the expression of SNAT2 DNA would enhance intracellular amino acid levels and increase their availability for protein synthesis.ResultsIn control myoblasts and myotubes, we found significantly decreased expression of SNAT2 (6.5× decrease, n = 4 per group, P < 0.05) in myotubes than found in myoblasts. After transfection with a SNAT2‐eGFP cDNA plasmid, C2C12 myoblasts significantly increased perinuclear punctate SNAT2‐eGFP expression that persisted and was more cytoplasmic after differentiation into myotubes. Interestingly, transfected cells were significantly more responsive to the hormone 5α‐dihydrotestosterone (DHT, 4.5 nM, by 1.6×, n = 3 per group, P < 0.04). Starvation significantly enhanced the amino acid C14‐MeAIB transport (1.7×, n = 3 per group, P < 0.05) indicating increased function of SNAT2. Inhibiting SNAT2 with high concentrations of MeAIB (3.3 or 5 mM) significantly reduced C14‐Isoleucine transport by L‐type amino acid transporter (LAT2, 52.8% and 77%, respectively, n = 3 per group, P < 0.05). However, there was no increase in the LAT2 transport of C14‐isoleucine detectable in SNAT2‐eGFP transfected cells after DHT (4.5 nM) exposure. This indicated that small amino acid availability was not rate limiting to LAT2 function in myoblasts.ConclusionsOverall, these data show that transfection of SNAT2‐eGFP expression enhanced its function following starvation and treatment with physiological levels of DHT. Enhanced SNAT2 expression in muscle cells offers a viable epigenetic target in pathological conditions associated with altered amino acid transport.

Frailty is Associated with Subsequent Development of Chronic Lung Allograft Dysfunction Following Lung Transplantation

PurposeChronic lung allograft dysfunction (CLAD) is a commonly recognized cause of death after lung transplantation. Frailty is a state of low physiologic reserve that frequently develops after lung transplantation, independent of allograft function. It is associated with increased risks of post-transplant readmission and mortality. Systemic inflammation is thought to be a potential cause of frailty and may contribute to development of CLAD. In this analysis, we hypothesized that the development of frailty after transplant may be associated with later development of CLAD.MethodsIn 259 lung transplant recipients, we measured frailty using the Short Physical Performance Battery (SPPB) at 3, 6, 12, 18, 24, 30, and 36 months after lung transplantation. Frailty was evaluated as a binary (SPPB ≤ 9) and continuous (1-point incremental worsening in SPPB) predictor (minimal clinically important difference = 1 point). The date of CLAD Grade 1 development was abstracted from our research database. Cox proportional hazards models were used to test the association between post-transplant frailty as a time-varying predictor and development of CLAD. Analyses were adjusted for pre-operative age, sex, race, diagnosis, and body mass index (BMI) measured at each visit.ResultsIn post-transplant follow-up, 115 patients (44%) were frail (SPPB ≤ 9); 129 patients (49%) ever demonstrated at least a 1-point worsening in SPPB. In unadjusted and adjusted analyses, frailty was associated with an increased risk of later developing CLAD. Frailty (SPPB ≤ 9) was associated with a 1.65-fold adjusted increased risk of CLAD. Further, one-point worsening in SPPB score was associated with a 1.08-fold increased risk of CLAD (Table).ConclusionFrailty is associated with increased subsequent risk of developing chronic lung allograft dysfunction following lung transplantation. Future studies should investigate mechanistic links between development of frailty post-transplant and subsequent risk of CLAD. Chronic lung allograft dysfunction (CLAD) is a commonly recognized cause of death after lung transplantation. Frailty is a state of low physiologic reserve that frequently develops after lung transplantation, independent of allograft function. It is associated with increased risks of post-transplant readmission and mortality. Systemic inflammation is thought to be a potential cause of frailty and may contribute to development of CLAD. In this analysis, we hypothesized that the development of frailty after transplant may be associated with later development of CLAD. In 259 lung transplant recipients, we measured frailty using the Short Physical Performance Battery (SPPB) at 3, 6, 12, 18, 24, 30, and 36 months after lung transplantation. Frailty was evaluated as a binary (SPPB ≤ 9) and continuous (1-point incremental worsening in SPPB) predictor (minimal clinically important difference = 1 point). The date of CLAD Grade 1 development was abstracted from our research database. Cox proportional hazards models were used to test the association between post-transplant frailty as a time-varying predictor and development of CLAD. Analyses were adjusted for pre-operative age, sex, race, diagnosis, and body mass index (BMI) measured at each visit. In post-transplant follow-up, 115 patients (44%) were frail (SPPB ≤ 9); 129 patients (49%) ever demonstrated at least a 1-point worsening in SPPB. In unadjusted and adjusted analyses, frailty was associated with an increased risk of later developing CLAD. Frailty (SPPB ≤ 9) was associated with a 1.65-fold adjusted increased risk of CLAD. Further, one-point worsening in SPPB score was associated with a 1.08-fold increased risk of CLAD (Table). Frailty is associated with increased subsequent risk of developing chronic lung allograft dysfunction following lung transplantation. Future studies should investigate mechanistic links between development of frailty post-transplant and subsequent risk of CLAD.

A Review of an Early Detection and Quantification of Osteoarthritis Severity in Knee using Machine Learning Techniques

The major cause of frailty in older and overweight people is Osteoarthritis. It is a joint illness that generally influences the ligament that could be principally affects the cartilage. Cartilage is a smooth elastic tissue which makes the bones move easily, stabilizes the joint and prevents them from abrading one another. The protective cartilage in Osteoarthritis is ruptured and makes the bones rub one another, inflicting joint stiffness and excessive pain. The current system for the assessment of Osteoarthritis incorporates clinical examination and restorative imaging methods. In this project, by utilizing profound features and medical images we need to recognize and classify OA affected in knee. This can impact on the detection and classification of target area in images and cause of it the irrelevant features could be selected from the medical images. This project will moreover center on dealing the colossal quantity of image information by using high speed computing. This paper also discovers the Magnetic Resonance imaging (MRI) techniques for detection and classification of Osteoarthritis in descriptive and comparative manner. Hence a coordinating discourse of different location strategies, highlight extraction procedures and classification methods regarding Osteoarthritis is worn out in a logical way.

Thrifty Hormone Ghrelin: The Secret of Aging Muscularly.

Sarcopenia is a debilitating muscle-wasting disease that is the major cause of frailty and disability in aging. Ghrelin (aka acylated ghrelin, AG) is a circulating peptide hormone with an unique octanoylation on Ser3. AG induces growth hormone (GH) secretion, increases food intake, and promotes adiposity and insulin resistance via its receptor, Growth Hormone Secretagogue Receptor (GHS-R). Unlike AG, unacylated ghrelin (UAG) is a peptide generated from the same ghrelin gene with amino acid sequence identical to AG but without the octanoylation modification, so UAG does not activate GHS-R. Intriguingly, both AG and UAG have been shown to promote differentiation and fusion of muscle C2C12 cells, regulate metabolic and mitochondrial signaling pathways in myotubes, and attenuate fasting- or denervation-induced muscle atrophy. Furthermore, it has also been shown that ghrelin gene deficiency increases vulnerability to fasting-induced muscle loss in aging mice, and AG and UAG effectively protects against muscle atrophy of aging mice. Because UAG doesn't bind to GHS-R, it doesn't have the undesired side-effects of elevated GH-release and increased obesity as AG. In summary, UAG has an impressive anti-atrophic effect in muscle protecting against muscle atrophy in aging, it has potential to be a unique and superior therapeutic candidate for muscle-wasting diseases such as sarcopenia.

Protein for Community-Dwelling Older People: Aspects That Influence the Perception of Commercially Available Protein Drinks.

In an aging population, support for independent living is increasingly critical for older generations. Currently, sarcopenia is a major cause of frailty, which increases the risk of decreased mobility, falls, morbidity, and mortality and leads to dependence on third parties. Sarcopenia is preventable by consumption of adequate protein. However, many older people do not meet the recommended daily allowance of protein, thereby supporting dependence rather than independent living. Current literature indicates that a protein drink could be an appropriate product for older peoples' protein consumption. We were interested in autonomous persons whose nutritional decisions were still self-determined and thus could preventively influence their personal health. This study evaluated three commercially available protein drinks in three focus groups (n = 25) to gain insight into which aspects influence the perception of commercial protein drinks on community-dwelling older people (age, 76.8 ± 4.9). Findings from the focus groups revealed only aspects, which influenced the perception of commercial protein drinks negatively. Most importantly, the drinks did not comply with relevant aspects when buying (healthy) foods, which where naturalness, freshness, locally grown ingredients, and trust. Furthermore, the target group did not see a need for additional protein consumption. Thus, we identify important aspects to be considered for the development of a target-group-specific protein drink as well as more suitable communication to prevent distrust in order to support independent living for community-dwelling older people.

The Willingness of Community Pharmacists in Collaborative Care of Frail Elderly in Nursing Homes

An increase in the number of residents in nursing homes has become a significant concern due to the rise in medication demand and subsequently medicationrelated issues, especially in frail elderly. Community pharmacists are the closest healthcare professionals available that can contribute to this population to allow optimal utilization of the prescribed drugs and to prevent drug-related problems. The present study aimed to investigate the awareness of community pharmacists on issues regarding frail elderly and to determine their willingness in collaborative care of frail elderly in nursing homes and the services they are willing to offer. This was a cross-sectional study utilising a set of questionnaire that was delivered to practicing community pharmacists in Peninsular Malaysia from June 2018 until December 2018. Majority of the participants agreed to the fact that aging is the primary cause of frailty (n=98, 88.3%), and that chronic disease is also a cause of frailty (n=96, 86.5%). Most of the community pharmacists were also keen to participate in the collaborative care of frail elderly, and were willing to provide their pharmacy service to the frail elderly. There was a positive correlation between the awareness of community pharmacists on issues regarding frail elderly and their willingness on collaborative care of frail elderly in nursing homes (r=0.374, n=111, p=0.01). Majority of the pharmacists were aware of the issues regarding the frail elderly, and were willing to participate in the collaborative care of frail elderly in nursing home.

CD19 CAR T-Cell Therapy in Patients with Relapse/Refractory DLBCL: Retrospective Analysis of the Eligibility Criteria

CD19 CAR T-Cell Therapy in Patients with Relapse/Refractory DLBCL: Retrospective Analysis of the Eligibility Criteria

Mecanismos fisiopatológicos de la sarcopenia en la EPOC

Sarcopenia is a disease characterized by loss of skeletal muscle, muscle strength and physical performance, being the major cause of frailty in the elderly. The sarcopenia is highly prevalent in individuals with Chronic obstructive pulmonary disease (COPD) leading to a poor prognosis and higher mortality in this population. The presence of sarcopenia in COPD is likely the result by the interaction between external and internal factors as systemic inflammation, oxidative stress and genetic polymorphisms, frequently observed in individuals with this respiratory disease. This review summarizes the current knowledge about the pathogenic mechanisms linking COPD with sarcopenia.

A novel nutritional supplement prevents muscle loss and accelerates muscle mass recovery in caloric-restricted mice

BackgroundMuscle atrophy is defined as decreased muscle mass, associated with aging as well as with various chronic diseases and is a fundamental cause of frailty, functional decline and disability. Frailty represents a huge potential public health issue worldwide with high impact on healthcare costs. A major clinical issue is therefore to devise new strategies preventing muscle atrophy. In this study, we tested the efficacy of Vital01, a novel oral nutritional supplement (ONS), on body weight and muscle mass using a caloric restriction-induced mouse model for muscle atrophy. MethodsMice were calorically restricted for 2 weeks to induce muscle atrophy: one control group received 60% kcal of the normal chow diet and one intervention group received 30% kcal chow and 30 kcal% Vital01. The effects on body weight, lean body mass, muscle histology and transcriptome were assessed. In addition, the effects of Vital01, in mice with established muscle atrophy, were assessed and compared to a standard ONS. To this end, mice were first calorically restricted on a 60% kcal chow diet and then refed with either 100 kcal% chow, a mix of Vital01 (receiving 60% kcal chow and 40 kcal% Vital01) or with a mix of standard, widely prescribed ONS (receiving 60 kcal% chow and 40 kcal% Fortisip Compact). ResultsVital01 attenuated weight loss (−15% weight loss for Vital01 vs. −25% for control group, p < 0.01) and loss of muscle mass (Vital01 with −13%, −12% and −18%, respectively, for gastrocnemius, quadriceps and tibialis vs. 25%, −23% and −28%, respectively, for control group, all p < 0.05) and also restored body weight, fat and muscle mass more efficiently when compared to Fortisip Compact. As assessed by transcriptome analysis and Western blotting of key proteins (e.g. phospoAKT, mTOR and S6K), Vital01 attenuated the catabolic and anabolic signaling pathways induced by caloric restriction and modulated inflammatory and mitochondrial pathways. In addition, Vital01 affected pathways related to matrix proteins/collagens homeostasis and tended to reduce caloric restriction-induced collagen fiber density in the quadriceps (with −27%, p = 0.051). ConclusionsWe demonstrate that Vital01 preserves muscle mass in a calorically restricted mouse model for muscle atrophy. Vital01 had preventive effects when administered during development of muscle atrophy. Furthermore, when administered in a therapeutic setting to mice with established muscle atrophy, Vital01 rapidly restored body weight and accelerated the recurrence of fat and lean body mass more efficiently than Fortisip Compact. Bioinformatics analysis of gene expression data identified regulatory pathways that were specifically influenced by Vital01 in muscle.

Effect of long‐term exercise on GDNF expression and innervation in rat skeletal muscle

Sarcopenia is a major cause of frailty and loss of independence in aging individuals. Results of recent studies suggest that changes in neural tissues may contribute to development of sarcopenia. Exercise provides neuroprotection by promoting neurogenesis, decreasing apoptosis, and modulating inflammation, however the mechanisms by which exercise generates these effects are not well understood. Neurotrophic factors are powerful regulators of neuronal maintenance and synaptic strength. Glial cell line‐derived neurotrophic factor (GDNF) is a neurotrophic factor that has been shown to be a potent survival factor for somatic motor neurons that innervate skeletal muscle, but as age continues, GDNF levels in muscle tend to decrease. This study seeks to expand our understanding of the regulatory processes controlling GDNF expression, which will aid in identifying how these processes become disturbed with aging, injury or in neurodegenerative diseases. Our hypothesis is that long‐term exercise will increase GDNF expression, and support neuromuscular junction (NMJ) structures. For these studies Sprague‐Dawley rats (6‐months of age) were exercised, in the form of voluntary running, for 6 months. Controls consisted of an age‐matched sedentary group maintained in cages without access to running wheels. After 6 months of exercise hind‐limb muscles were collected and processed for measurement of GDNF protein content via enzyme‐linked immunosorbent assay. The length and area of motor end plates were quantified via staining with a‐bungarotoxin. Immunohistochemical analysis was performed to detect co‐localization of GDNF and choline acetyltransferase (ChAT), using antibodies against GDNF and ChAT. There was a significant (p ≤ 0.05) increase in length of stained end plates in muscles from exercised rats (36.6 ± 3.5μm) when compared to that in the age‐matched sedentary group (27.6 ± 1.15μm). There was a significant (p ≤ 0.05) increase in area of stained end plates in muscles from exercised rats (616.3 ± 84.9μm2) when compared to that in the age‐matched sedentary group (430.3 ± 30.8μm2). We also observed a trend towards an increase GDNF protein content in muscle from exercised rats compared to tissues from sedentary control rats; however, the effect was not significant. Although, co‐localization between GDNF and ChAT appeared more apparent in tissues from exercised rats. These findings suggest that increased physical activity enhances structural neuroplasticity in NMJ elements and may possibly lead to enhanced neuromuscular function. Understanding the activity dependent regulation of neurotrophic factor expression and neural plasticity in the neuromuscular system may help in identifying novel targets for pharmacological development.Support or Funding InformationThis work was supported by a grant from the Faculty Research and Creative Activities Award, Western Michigan University, NIH grant 1 R15 AG022908‐01A2, NSF grant DBI 0552517.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Elderly Characteristics with Frailty Syndrome by Frailty Index Questionnaire – 40 (FI - 40) at Bandung Nursing Home

Frailty syndrome is a state of decreased body function, thereby increasing susceptibility to poor clinical outcomes. The risks of developing frailty syndrome increase in the elderly at Nursing Home. This study is expected to provide characteristic data of frailty syndrome as the basis for the prevention and management for the elderly. This study is conducted by using a descriptive quantitative design. The data is taken by using FI-40 questionnaire consisting of 40 questions in the elderly at Bandung done by using total sampling. There are 42(58.3%) of pre-frail and 7(9.7%) of frail elderly out of 72 data. Pre-frail prevails mostly in women (29 subjects; 69.1%) and at age of 60-69 years in 18 subjects (42.8%). Frail elderly is found mostly in women (3 subjects; 42.8%) and aged 70-79 years (3 subjects ; (42.8). The most common cause of frailty is eye and foot problems in 7(100%). The most common cause of pre-frail is the assumption of health level in 35(83.3%). This study concludes that frailty syndrome is common among the elderly and special attention must be paid to eye and foot problems.Keywords: elderly, frailty syndrome, FI-40 questionnaire, nursing home

Association Between Immunosenescence Phenotypes and Pre-frailty in Older Subjects: Does Cytomegalovirus Play a Role?

Frailty is highly prevalent in old age and confers an important mortality risk. Although the causes of frailty are multiple, immunosenescence (IS)-predominantly driven by cytomegalovirus (CMV)-has been implicated in its pathophysiology. Thus far, research examining the association between IS and frailty states is sparse and equivocal. On the other hand, evidence is mounting in support of the view that frailty can be reversed, especially for those in the pre-frail stage. Therefore, we aimed to clarify the impact of CMV on IS and its relevance to pre-frailty. One hundred seventy-three persons aged 80 to 99 years were enrolled. Pre-frailty was defined according to Fried's criteria. Anti-CMV IgG and serum IL-6 were measured using Architect iSystem and Luminex, respectively. T-cell phenotypes were determined using flow cytometry. The prevalence of pre-frailty was 52.6%, increased with age (p = .001), and was greater in men than women (p = .044). No relationship was found between pre-frailty and positive CMV serology. Further, CMV-seropositivity was significantly associated with less naïve cells, more memory and senescence-prone phenotypes (all p < .001). After adjusting for potential confounders, only IL-6, age and sex were predictive of pre-frailty. We conclude that the presence of pre-frailty is independent from CMV infection in very old subjects.

Approach to frailty in the elderly in primary care and the community.

Frailty is a distinct clinical syndrome wherein the individual has low reserves and is highly vulnerable to internal and external stressors. Although it is associated with disability and multiple comorbidities, it can also be present in individuals who seem healthy. Frailty is multidimensional and its pathophysiology is complex. Early identification and intervention can potentially decrease or reverse frailty, especially in the early stages. Primary care physicians, community nurses and community social networks have important roles in the identification of pre-frail and frail elderly through the use of simple frailty screening tools and rapid geriatric assessments. Appropriate interventions that can be initiated in a primary care setting include a targeted medical review for reversible medical causes of frailty, medication appropriateness, nutritional advice and exercise prescription. With ongoing training and education, the multidisciplinary engagement and coordination of care of the elderly in the community can help to build resilience and combat frailty in our rapidly ageing society.

Frailty and sarcopenia in elderly.

Frailty is apre-disability syndrome where an older person can be identified as being at risk when exposed to stressors associated with high risk for disability or needing to be hospitalized. Two major frailty definitions exist. The physical phenotype of frailty and the multiple deficit model. Asimple frailty screening tool-FRAIL-has been validated. Treatment of frailty involves resistance exercise, optimization of nutrition, and treatment of fatigue (sleep apnea, depression), treatable causes of weight loss and adjustment of polypharmacy. Sarcopenia (decline in function with low muscle mass) is amajor cause of frailty. Asimple sarcopenia screening tool-SARC-F-has been validated. The multiple causes of sarcopenia are reviewed. Optimal treatment is resistance exercise, leucine-enriched essential amino acids and vitaminD replacement.

Comparing two frailty concepts among older people with intellectual disabilities

In general, disabilities are considered a consequence of frailty rather than a cause of frailty, whereas in people with intellectual disabilities (ID), disabilities are often lifelong, which could have consequences for the feasibility and validity of frailty instruments. To better understand frailty in people with ID, we compared two broadly used concepts: the frailty phenotype (FP) and the frailty index (FI) taking into account their feasibility (e.g., percentage of participants able to complete the frailty assessments), agreement, validity (based on 5-year mortality risk), influence of motor disability, and the relation between single frailty variables and mortality. The FI and an adapted version of the FP were applied to a representative dataset of 1050 people with ID, aged 50 years and over. The FI was feasible in a larger part of the dataset (94 %) than the adapted FP: 29 % for all five items, and 81 % for at least three items. There was a slight agreement between the approaches (κ = 0.3). However defined, frailty was related with mortality, but the FI showed higher discriminative ability and a stronger relation with mortality, especially when adjusted for motor disabilities. Concluding, these results imply that the used FI is a stronger predictor for mortality and has higher feasibility than our adaptation of the FP, in older people with ID. Possible explanations of our findings are that we did not use the exact FP variables or that the FI includes multiple health domains, and the variables of the FI have lower sensitivity to lifelong disabilities and are less determined by mobility.

Chronic kidney disease-related physical frailty and cognitive impairment: a systemic review.

The objective of this review was to assess chronic kidney disease-related frailty and cognitive impairment, as well as their probable causes, mechanisms and the interventions. Studies from 1990 to 2015 were reviewed to evaluate the relationship between chronic kidney disease and physical frailty and cognitive impairment. Of the 1694 studies from the initial search, longitudinal studies (n = 22) with the keywords "Cognitive and CKD" and longitudinal or cross-sectional studies (n = 5) with the keywords "Frailty and CKD" were included in final analysis. By pooling current research, we show clear evidence for a relationship between chronic kidney disease and frailty and cognitive impairment in major studies. Vascular disease is likely an important mediator, particularly for cognitive impairment. However, non-vascular factors also play an important role. Many of the other mechanisms that contribute to impaired cognitive function and increased frailty in CKD remain to be elucidated. In limited studies, medication therapy did not obtain the ideal effect. There are limited data on treatment strategies, but addressing the vascular disease risk factors earlier in life might decrease the subsequent burden of frailty and cognitive impairment in this population. Multidimensional interventions, which address both microvascular health and other factors, may have substantial benefits for both the cognitive impairments and physical frailty in this vulnerable population. Chronic kidney disease is a potential cause of frailty and cognitive impairment. Vascular and non-vascular factors are the possible causes. The mechanism of chronic kidney disease-induced physical frailty and cognitive impairment suggests that multidimensional interventions may be effective therapeutic strategies in the early stage of chronic kidney disease. Geriatr Gerontol Int 2017; 17: 529-544.

Prevalence and incidence of frailty in Aboriginal Australians, and associations with mortality and disability

ObjectivesFrailty represents a loss of homeostasis, markedly increasing the risk of death and disability. Frailty has been measured in several ethnic groups, but not, to our knowledge, in Aboriginal Australians. We aimed to determine the prevalence and incidence of frailty, and associations with mortality and disability, in remote-living Aboriginal people. Study designBetween 2004 and 2006, we recruited 363 Aboriginal people aged ≥45 years from 6 remote communities and one town in the Kimberley region of Western Australia (wave 1). Between 2011 and 2013, 182 surviving participants were followed-up (wave 2). We assessed frailty with an index, comprising 20 health-related items. Participants with ≥4 deficits (frailty index ≥0.2) were considered frail. Disability was assessed by family/carer report. Those unable to do ≥2 of 6 key or instrumental activities of daily living were considered disabled. We investigated associations between frailty, and disability and mortality, with logistic regression and Cox proportional hazards models. ResultsAt wave 1 (W1), 188 participants (65.3%) were frail, and of robust people at W1 who participated in wave 2, 38 (51.4%) had become frail. Frailty emerged at a younger age than expected. A total of 109 people died (30.0%), of whom 80 (73.4%) were frail at W1. Frailty at W1 was not associated with becoming disabled, but was associated with mortality (HR=1.9; 95% CI 1.2, 3.0). ConclusionsFrailty in remote-living Aboriginal Australians is highly prevalent; substantially higher than in other populations. Research to understand the underlying causes of frailty in this population, and if possible, reverse frailty, is urgently needed.

MicroRNA-Regulated Proinflammatory Cytokines in Sarcopenia.

Sarcopenia has been defined as the aging-related disease with the declined mass, strength, and function of skeletal muscle, which is the major cause of frailty and falls in elders. The activation of inflammatory signal pathways due to diseases and aging is suggested to reveal the critical impact on sarcopenia. Several proinflammatory cytokines, especially interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), play crucial roles in modulation of inflammatory signaling pathway during the aging-related loss of skeletal muscle. MicroRNAs (miRNAs) have emerged as the important regulators for the mass and functional maintenance of skeletal muscle through regulating gene expression of proinflammatory cytokines. In this paper, we have systematically discussed regulatory mechanisms of miRNAs for the expression and secretion of inflammatory cytokines during sarcopenia, which will provide some novel targets and therapeutic strategies for controlling aging-related atrophy of skeletal muscle and corresponding chronic inflammatory diseases.