Inhibition of IL-11 signalling extends mammalian healthspan and lifespan.

For healthspan and lifespan, ERK, AMPK and mTORC1 represent critical pathways and inflammation is a centrally important hallmark1-7. Here we examined whether IL-11, a pro-inflammatory cytokine of the IL-6 family, has a negative effect on age-associated disease and lifespan. As mice age, IL-11 is upregulated across cell types and tissues to regulate an ERK-AMPK-mTORC1 axis to modulate cellular, tissue- and organismal-level ageing pathologies. Deletion of Il11 or Il11ra1 protects against metabolic decline, multi-morbidity and frailty in old age. Administration of anti-IL-11 to 75-week-old mice for 25 weeks improves metabolism and muscle function, and reduces ageing biomarkers and frailty across sexes. In lifespan studies, genetic deletion of Il11 extended the lives of mice of both sexes, by 24.9% on average. Treatment with anti-IL-11 from 75 weeks of age until death extends the median lifespan of male mice by 22.5% and of female mice by 25%. Together, these results demonstrate a role for the pro-inflammatory factor IL-11 in mammalian healthspan and lifespan. We suggest that anti-IL-11 therapy, which is currently in early-stage clinical trials for fibrotic lung disease, may provide a translational opportunity to determine the effects of IL-11 inhibition on ageing pathologies in older people.

Plant proteins: are they a good alternative to animal proteins in older people?

PURPOSE OF REVIEW: This review provides the latest insight into the impact of consuming plant-based protein for older people. RECENT FINDINGS: According to the latest data, a healthy diet rich in plant-based-protein-rich-food could promote healthy aging. This health effect is partly because of the amino acid composition of proteins, as well as to the important constituents such as fiber and bioactive compounds found in the matrix. Furthermore, even though animal protein is more effective at stimulating muscle protein synthesis, a high consumption of plant protein (beyond 31 g/day) appears to enhance physical performance and reduce the risk of frailty in older individuals. SUMMARY: Recent literature highlights numerous health benefits for older people associated with a substantial intake of plant-based vs. animal-based protein, both in preventing and mitigating chronic age-related diseases and reducing the risk of all-cause mortality. However, a high intake of plant-based protein-rich products could pose risks of malnutrition and fiber-related intestinal intolerances. Further research is needed to assess the risk-benefit ratio of a high consumption of plant proteins in older individuals before we can make robust recommendations on how far animal proteins can be healthfully replaced with plant proteins.

Effectiveness of interventions to prevent or reverse pre-frailty and frailty in middle-aged community dwelling adults: A systematic review.

INTRODUCTION: Frailty, marked by diminished physiological capacity and higher health risks, is less understood in middle-aged individuals (40-65 years) than older adults. This review synthesises intervention studies for pre-frailty and frailty in this demographic, assessing effectiveness, feasibility, and implementation factors including participant experience and cost-effectiveness. METHOD: Registered on the Open Science Framework and adhering to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and the template for intervention description and replication (TIDieR) guidelines, this review searched six databases for interventions targeting middle-aged adults. Dual screening, data extraction, risk assessment, and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) certainty evaluation were conducted. Findings were narratively synthesized due to heterogeneity. RESULTS: Eight studies (2018-2023) with 2838 participants were included. Resistance training and multicomponent exercise reduced frailty; though, not always significantly. Low-intensity exercises and education-based interventions yielded mixed results, suggesting a need for further research. Positive participant experiences and cost-effectiveness of interventions such as resistance training and educational interventions supports their feasibility. Varying quality, methodologies and levels of bias indicated a need for more rigorous future research. DISCUSSION: This review reveals an evidence gap in middle-aged frailty interventions. Multicomponent interventions and resistance training showed promise, but their comparative effectiveness remains uncertain. Educational and low-intensity interventions need further research to establish their effectiveness. The findings diverge from those in older adults, emphasising the need for age-specific approaches. Future studies should employ higher-quality methods and explore emerging technologies to enhance intervention effectiveness for pre-frailty and frailty in middle-aged adults.

Higher plant-derived nitrate intake is associated with lower odds of frailty in a cross-sectional study of community-dwelling older women.

PURPOSE: Dietary nitrate intake is inversely related to numerous contributors towards frailty, including cardiovascular disease and poor physical function. Whether these findings extend to frailty remain unknown. We investigated if habitual nitrate intake, derived from plants or animal-based foods, was cross-sectionally associated with frailty in women. METHODS: Community-dwelling older Australian women (n = 1390, mean age 75.1 ± 2.7 years) completed a validated semi-quantitative food frequency questionnaire (FFQ). Nitrate concentrations in food were obtained from international nitrate databases. We adopted the Rockwood frailty index (FI) of cumulative deficits comprising 33 variables across multiple health domains (scored 0 to 1), which predicts increased hospitalisation and mortality risk. A FI ≥ 0.25 indicated frailty. Cross-sectional associations between nitrate intake (total plant and animal nitrate, separately) and frailty were analysed using multivariable-adjusted logistic regression models (including lifestyle factors), as part of restricted cubic splines. RESULTS: A non-linear inverse relationship was observed between total plant nitrate intake and frailty. Compared to women with the lowest plant nitrate intake (Quartile [Q]1), women with greater intakes in Q2 (OR 0.69 95%CI 0.56-0.84), Q3 (OR 0.67 95%CI 0.50-0.90) and Q4 (OR 0.66 95%CI 0.45-0.98) had lower odds for frailty. A nadir in the inverse association was observed once intakes reached ~ 64 mg/d (median Q2). No relationship was observed between total animal nitrate and frailty. CONCLUSION: Community-dwelling older women consuming low amounts of plant-derived nitrate were more likely to present with frailty. Consuming at least one daily serving (~ 75 g) of nitrate-rich green leafy vegetables may be beneficial in preventing frailty.

Summary of best evidence for prevention and management of frailty.

BACKGROUND: Frailty in older people can seriously affect their quality of life and increase the demand for long-term care and health care expenses. Aims of this study are to provide an evidence-based basis for clinical practice of frailty in older people by systematically searching for the best current evidence on interventions for the prevention and management of frailty. METHODS: According to the '6S' evidence resource model, evidence retrieval is searched from the top-down and collected relevant guidelines, best practices, evidence summaries, systematic reviews and expert consensus. The retrieval time limit was from the database establishment to 20 March 2023. Two reviewers independently screened and evaluated the literature, and then extracted and summarised the evidence according to the JBI grading of evidence and recommendation system. RESULTS: A total of 44 publications were finally included, including 12 guidelines, 5 best practices, 4 expert consensus, 5 evidence summaries and 18 systematic reviews. Through the induction and integration of the evidence, the evidence was finally summarised from eight aspects: frailty screening, frailty assessment, exercise intervention, nutrition intervention, multi-domain intervention, drug administration, social support and health education, and 43 best evidences were formed. CONCLUSIONS: This study summarised the best evidence for the prevention and management of frailty from eight aspects, which can provide guidance for clinical or community medical staff to develop and apply frailty intervention and practice programmes for older people and improved the clinical outcome and quality of life of older people.

Quality of plant-based diets and frailty incidence: a prospective analysis of UK biobank participants.

BACKGROUND: Substantial evidence supports the inverse association between adherence to healthy dietary patterns and frailty risk. However, the role of plant-based diets, particularly their quality, is poorly known. OBJECTIVE: To examine the association of two plant-based diets with incidence of physical frailty in middle-aged and older adults. DESIGN: Prospective cohort. SETTING: United Kingdom. SUBJECTS: 24,996 individuals aged 40-70 years, followed from 2009-12 to 2019-22. METHODS: Based on at least two 24-h diet assessments, we built two diet indices: (i) the healthful Plant-based Diet Index (hPDI) and (ii) the unhealthful Plant-based Diet Index (uPDI). Incident frailty was defined as developing ≥3 out of 5 of the Fried criteria. We used Cox models to estimate relative risks (RR), and their 95% confidence interval (CI), of incident frailty adjusted for the main potential confounders. RESULTS: After a median follow-up of 6.72 years, 428 cases of frailty were ascertained. The RR (95% CI) of frailty was 0.62 (0.48-0.80) for the highest versus lowest tertile of the hPDI and 1.61 (1.26-2.05) for the uPDI. The consumption of healthy plant foods was associated with lower frailty risk (RR per serving 0.93 (0.90-0.96)). The hPDI was directly, and the uPDI inversely, associated with higher risk of low physical activity, slow walking speed and weak hand grip, and the uPDI with higher risk of exhaustion. CONCLUSIONS: In British middle-age and older adults, greater adherence to the hPDI was associated with lower risk of frailty, whereas greater adherence to the uPDI was associated with higher risk.

Physical activity, sedentary behavior, and the risk of frailty and falling: A Mendelian randomization study.

BACKGROUND: Due to inconclusive evidence from observational studies regarding the impact of physical activity (PA) and sedentary behavior on frailty and falling risk, we conducted a two-sample Mendelian randomization analysis to investigate the causal associations between PA, sedentary behavior, and frailty and falls. METHODS: We extracted summary data from genome-wide association studies conducted among individuals of European ancestry, encompassing PA (n = 90 667-608 595), sedentary behavior (n = 372 609-526 725), frailty index (n = 175 226), and falling risk (n = 451 179). Single nucleotide polymorphisms associated with accelerometer assessed fraction >425 milligravities, self-reported vigorous activity, moderate to vigorous physical acticity (MVPA), leisure screen time (LST), and sedentary behavior at work were taken as instrumental variables. The causal effects were primarily estimated using inverse variance weighted methods, complemented by several sensitivity and validation analyses. RESULTS: Genetically predicted higher levels of PA were significantly associated with a reduction in the frailty index (accelerometer assessed fraction >425 milligravities: ß = -0.25, 95% CI = -0.36 to -0.14, p = 1.27 × 10-5 ; self-reported vigorous activity: ß = -0.13, 95% CI = -0.20 to -0.05, p = 7.9 × 10-4 ; MVPA: ß = -0.28, 95% CI = -0.40 to -0.16, p = 9.9 × 10-6 ). Besides, LST was significantly associated with higher frailty index (ß = 0.18, 95% CI = 0.14-0.22, p = 5.2 × 10-20 ) and higher odds of falling (OR = 1.13, CI = 1.07-1.19, p = 6.9 × 10-6 ). These findings remained consistent throughout sensitivity and validation analyses. CONCLUSIONS: Our study offers evidence supporting a causal relationship between PA and a reduced risk of frailty. Furthermore, it underscores the association between prolonged LST and an elevated risk of frailty and falls. Therefore, promoting PA and reducing sedentary behavior may be an effective strategy in primary frailty and falls prevention.

Reliability, validity and minimal detectable change of the Chinese Version of the Assessment of Physical Activity in Frail Older People (APAFOP-C).

BACKGROUND: Physical activity (PA) is essential in mitigating frailty syndrome, and it is necessary to measure PA in older adults with frailty. Assessment of Physical Activity in Frail Older People (APAFOP) is a suitable patient-reported outcome measure (PROM) for assessing PA among older adults with frailty. This study aimed to determine the reliability, validity and minimal detectable change of the Chinese version of the APAFOP (APAFOP-C). METHODS: This cross-sectional validation study was designed to measure the reliability and criterion validity of the APAFOP-C with 124 frail community-residing older adults. APAFOP-C was completed twice within an interval of 7-17 days to determine test-retest reliability. The investigator triangulation method was used to investigate inter-rater reliability, and a pedometer was used as the reference measurement to assess the criterion validity. Reliability and criterion validity were assessed using the intraclass correlation coefficient (ICC2,1), Pearson correlation coefficient for normally distributed variables, Spearman correlation coefficient, Wilcoxon signed-rank test for skewed variables, and the minimal detectable change at 95% level of confidence (MDC95). Agreement assessment was conducted using Bland-Altman plots for inter-rater reliability and criterion validity. Kendall's W test assessed absolute agreement among three raters in inter-rater reliability. The Mann-Whitney U test was used to evaluate whether any particular day was more representative of certain daily activities. RESULTS: Total PA on any arbitrarily chosen day illustrates daily activity (Z= -0.84, p = 0.40). The APAFOP-C exhibited strong-to-very strong test-retest reliability (ICC2,1=0.73-0.97; Spearman ρ = 0.67-0.89), and the total PA score demonstrated MDC95 < 10%. Inter-rater reliability was also strong-to-very strong (ICC2,1=0.96-0.98; Spearman ρ = 0.88-1.00), and moderate criterion validity when compared with total PA score on pedometer readings (Spearman ρ = 0.61). Limits of agreement among different raters regarding the APAFOP-C and the pedometer were narrow. CONCLUSION: The APAFOP-C was found to have limited but acceptable psychometric properties for measuring PA among community-dwelling older adults with frailty in China. It was a feasible comparative PROM for assessing PA worldwide. Practitioners can develop individualized exercise programs for frail older adults and efficiently track changes in PA utilizing the APAFOP-C.

Association of cooking oil and incident of frailty in older adults: a cohort study.

BACKGROUND: Studies examining the potential association between cooking oil and frailty risk in older adults have produced conflicting outcomes. Therefore, our objective was to explore the relationship between cooking oil (vegetable and animal fat oils), changes in oil usage, and the risk of frailty in older adults. METHODS: We included 4,838 participants aged ≥ 65 years without frailty (frailty index < 0.25) from the 2011 wave of the Chinese Longitudinal Healthy Longevity Survey. Follow-up occurred in the 2014 and 2018 waves. Cox proportional hazard models were utilized to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) to examine the association between cooking oil and frailty. Additionally, we evaluated the effect of switching cooking oil on frailty during the follow-up period. RESULTS: During a median follow-up of 3.0 (2.8-6.9) years, 1,348 individuals (27.9%) developed frailty. Compared to those using vegetable oil, users of animal fat oil had a lower risk of frailty (HR = 0.72, 95% CI: 0.61-0.85). Participants who switched from vegetable oil to animal fat oil, as well as those consistently using animal fat oil, had lower risks of frailty with HRs of 0.70 (0.52-0.95) and 0.63 (0.51-0.77) respectively, compared to those who consistently used vegetable oil. Conversely, individuals who switched from animal fat oil to vegetable oil experienced an increased risk of frailty (HR: 1.41, 95% CI: 1.01-1.97). CONCLUSIONS: The utilization of animal fat oil in cooking exhibited a reduced frailty risk among older adults. Conversely, transitioning from animal fat oil to vegetable oil may elevate the risk. These findings propose that substituting vegetable oil with animal fat oil in the diet may safeguard against frailty.

POSITIVE: experiences of an intervention aiming for reversing and preventing frailty using a home monitoring and communication platform within primary health care.

BACKGROUND: Frailty is increasing worldwide as the population ages. Physical activity is one component that has been shown to hinder and even reverse the process. The POSITIVE system (i.e., maintaining and imPrOving the intrinSIc capaciTy Involving primary care and caregiVErs) is a prevention program that consists of home-monitoring equipment and a communication platform to support the initial treatment of frailty symptoms in primary health care. The participants, older aged (+ 70) frail persons and those at risk for frailty, took part in the program that promoted physical activity at home for six months. The aim was to explore and describe older persons' experiences of participating in a new prevention program using the POSITIVE system including technological tools intended to prevent the development of frailty. METHODS: Nine interviews were conducted about experiences of participating in an intervention including use of technological tools to support physical activity. Qualitative content analysis was applied. RESULTS: Two themes revealed: (1) Perceptions of being old are seldom positive, and (2) A rewarding and fruitful participation in the project with suggestions for improvement. Becoming older was related to physical pain and tiredness reducing the performance of former meaningful activities as well as an increase in mental stress. There was also a tendency to postpone the start of everyday activities, and in general, fewer activities were planned for one day than at younger ages. Participating in a physical activity intervention, including the use of technical tools, was considered meaningful and added motivation for engaging in other physical activities, this despite some difficulties with technical tools provided by the program. The contact with health care and the research team was appreciated. In addition, contact with other participants was requested and reported to be highly valued if added to the intervention, which could have been an expression of loneliness. CONCLUSION: Participation in a prevention program motivated activities and social interaction. Adding opportunities for participants to meet each other is suggested for improving the intervention in terms of increasing the social dimensions. Our findings conclude that despite difficulties with handling the technical tools for the home-monitoring and communication platform, participation in the POSITIVE intervention was in general a positive experience.

Combining motivational and exercise intervention components to reverse pre-frailty and promote self-efficacy among community-dwelling pre-frail older adults: a randomized controlled trial.

BACKGROUND: Exercise is effective in preventing frailty status in older adults, but the effect of an exercise program based on Wellness Motivation Theory (WMT) on the frailty status, self-efficacy for exercise, and quality of life for older adults with pre-frailty remains unclear. Our objective was to examine the efficacy of a multicomponent exercise program based on WMT on frailty status, self-efficacy, and quality of life among pre-frail older adults. METHODS: This was a randomized controlled trial of pre-frail older adults aged from 60 years to 85 years. Participants in the intervention group performed exercise three times a week for 24 weeks, once at a community health service station instructed by two researchers and two times at home. Participants in the control group were given one-time advice on physical activity. The assessor was the only one blinded. The primary outcome was the reversal rate of pre-frailty. The secondary outcomes included self-efficacy and quality of life. RESULTS: One hundred and forty-four participants were randomized into two groups (n = 72 in the intervention group and n = 72 in the control group) and analyzed. After 24 weeks, the proportion of pre-frailty was significantly lower in the intervention group than in control (31.8% versus 74.6%, P < 0.001). The absolute risk reduction was 42.8% [95% CI, 25.1-57.1]. In the 8th week and the 24th week, the frailty score of the intervention group was significantly lower than that of the control group. There were significant improvements in self-efficacy at week 2, week 8, and week 24. In weeks 8 and 24, participants in the intervention group reported a higher quality of life than the control group. There were no exercise-related injuries or falls among the participants. CONCLUSIONS: The exercise intervention based on WMT for pre-frail older adults could reverse pre-frailty, increase self-efficacy for exercise, and improve the quality of life in older Chinese. STUDY REGISTRATION DETAILS: This study was registered in www. CLINICALTRIALS: gov on the 25th of July, 2024, with the identifier NCT06519695. REPORTING METHOD: The Consolidated Standards of Reporting Trials (CONSORT) checklist was used in this study for properly reporting how the randomized trial was conducted.

The interaction between Mediterranean diet and intestinal microbiome: relevance for preventive strategies against frailty in older individuals.

Age-related changes in intestinal microbiome composition and function are increasingly recognized as pivotal in the pathophysiology of aging and are associated with the aging phenotype. Diet is a major determinant of gut-microbiota composition throughout the entire lifespan, and several of the benefits of a healthy diet in aging could be mediated by the microbiome. Mediterranean diet (MD) is a traditional dietary pattern regarded as the healthy diet paradigm, and a large number of studies have demonstrated its benefits in promoting healthy aging. MD has also a positive modulatory effect on intestinal microbiome, favoring bacterial taxa involved in the synthesis of several bioactive compounds, such as short-chain fatty acids (SCFAs), that counteract inflammation, anabolic resistance, and tissue degeneration. Intervention studies conducted in older populations have suggested that the individual response of older subjects to MD, in terms of reduction of frailty scores and amelioration of cognitive function, is significantly mediated by the gut-microbiota composition and functionality. In this context, the pathophysiology of intestinal microbiome in aging should be considered when designing MD-based interventions tailored to the needs of geriatric patients.

Prevention at home in older persons with (pre-)frailty: analysis of participants' recruitment and characteristics of the randomized controlled PromeTheus trial.

BACKGROUND: The "PromeTheus" trial is evaluating a home-based, multifactorial, interdisciplinary prevention program for community-dwelling (pre-)frail older adults. These individuals often suffer from reduced participation, which can complicate the recruitment and enrollment in a clinical trial. AIMS: The aim of this study was to evaluate different recruitment strategies and differences in participant characteristics in relation to these strategies. METHODS: This cross-sectional study used baseline data from the randomized-controlled PromeTheus trial, in which community-dwelling (pre-)frail older persons (Clinical Frailty Scale [CFS] 4-6 pt., ≥ 70 years) were recruited via general practitioners ("GP recruitment") or flyers, newspaper articles, and personalized letters ("direct recruitment"). Differences in the sociodemographic, clinical, physical, functional, mobility-related, psychological and social characteristics were analyzed in relation to the recruitment strategy. RESULTS: A total of 385 participants (mean age = 81.2, SD 5.9 years; women: n = 283, 73.5%) were enrolled, of which 60 (16%) were recruited by GPs and 325 (84%) through direct recruitment. Participants recruited via GPs had significantly higher subjective frailty levels (CFS), were more often physically frail (Fried Frailty Phenotype), and showed lower physical capacity (Short Physical Performance Battery), participation (disability component of the short version of the Late-Life Function and Disability Instrument), and life-space mobility (Life-Space Assessment) compared to those recruited via the direct approach (p = 0.002-0.026). Costs per randomized participant were 94€ for the GP recruitment strategy and €213 for the direct recruitment strategy. CONCLUSION: Different strategies may be required to successfully recruit (pre-)frail home-living older adults into preventive programs. Direct recruitment strategies, in which potential participants are directly informed about the prevention program, seem to be more promising than GP recruitment but may result in enrolment of persons with less functional impairment and higher recruitment costs. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00024638. Registered on March 11, 2021.

One-bite-sized 3D printed finger foods, oriented to malnutrition, sarcopenia and frailty prevention in the older people.

BACKGROUND: In this study, innovative chocolate, citrus and mixture flavoured tofu-based nutritionally customised, dysphagia-oriented, comfortably consumed, appetising, one-bite-sized finger foods, oriented to malnutrition, sarcopenia and frailty prevention in older people were created by using 3D printing technology. Developed products were characterised by evaluating chemical composition and physical properties and performing sensory evaluation among geriatric clinic residents (≥60 years). RESULTS: The dietary composition of the developed foods was: 19-21 g (100 g)-1 protein, 6-8 g (100 g)-1 fibre, 8-9 g (100 g)-1 fat, 11 mg (100 g)-1 iron, 14 mg (100 g)-1 zinc, 70 µg (100 g)-1 selenium. Foods were also enriched with branched-chain amino acids, such as leucine, isoleucine and valine. All formulated foods were classified as level 6 by International Dysphagia Diet Standardisation Initiative classification. Chocolate-flavoured food was much harder (4914 g) with lower adhesiveness value (-33.6 g s), compared to the citrus- or mixture-flavoured foods. Older people evaluated all finger foods as very easy handled by hand, soft, easy to swallow, having a moderate flavour intensity and a weak afterfeel. Despite the fact that the chocolate food was evaluated as having the highest hardness and gumminess values by the instrumental method, this difference was not noticeable to the evaluators. However 7% of the participants said that 3D printed foods were sticky to dentures. CONCLUSION: The results suggest that it is possible to create nutrient-dense comfortably consumed 3D printed foods, oriented to malnutrition, sarcopenia and frailty prevention in older people. © 2024 Society of Chemical Industry.

[Prevention of frailty]. / Prävention der Frailty.

BACKGROUND: The presence of frailty in older patients increases the risk for adverse health events and for a loss of independence. Measures for the prevention of this geriatric syndrome should be incorporated into routine healthcare. OBJECTIVE: What types of interventions could be effective in the prevention of frailty and how can preventive strategies be successfully implemented? METHOD: Narrative review article. RESULTS: The concept of frailty is multidimensional and potential starting points for a prevention of frailty can be found within different dimensions (e.g., dimensions of physical activity and nutrition, psychosocial dimension). Epidemiological analyses have identified factors that increase or decrease the risk for becoming frail. Evidence from randomized controlled trials that examined the effectiveness of specific interventions in the prevention of frailty is still limited. Based on the available data, interventions using physical exercise appear to be effective in preventing frailty. In primary care in Germany the frailty status of older patients is not yet routinely recorded, which impedes the identification of patients at risk (patients with pre-frailty) and the implementation of targeted preventive strategies. The Integrated Care for Older People (ICOPE) concept of the World Health Organization offers a potential approach to prevent frailty and to promote healthy ageing within the population. CONCLUSION: The prevention of frailty is possible and reasonable. Comprehensive and targeted preventive strategies are yet to be implemented.

Frailty is associated with increased risk of cirrhosis disease progression and death.

BACKGROUND AND AIMS: The Liver Frailty Index (LFI) is a well-studied tool that evaluates frailty in patients with cirrhosis. Consisting of grip strength, chair stands, and balance testing, the LFI has been associated with increased mortality in patients awaiting liver transplant. We aimed to extend our understanding of frailty in cirrhosis by exploring the relationship between the LFI and the risk of (1) cirrhosis progression, (2) mortality, and (3) unplanned hospitalizations, in both compensated and decompensated disease. APPROACH AND RESULTS: Adult patients with cirrhosis from four centers in North America and one in India were included. Frailty was measured at baseline using the LFI and categorized as robust (LFI < 3.2), prefrail (LFI 3.2-4.5), and frail (LFI > 4.5). Progression of cirrhosis was defined by an increase in clinical stage, ranging from 1 to 5, from baseline using the D'Amico classification. Factors associated with progression, mortality, and hospitalizations were evaluated using multivariate regression models, with transplant as a competing risk. In total, 822 patients with cirrhosis were included. Average Model for End-Stage Liver Disease (MELD) score was 15.5 ± 6.0. In patients with compensated cirrhosis, being frail versus robust was associated with increased risk of progression to the next cirrhosis stage or to death (HR, 2.45; 95% CI, 1.14-5.29) and with an increased risk of unplanned hospitalizations (2.32; 95% CI, 1.13-4.79), after adjusting for age, sex, and MELD score. Similar HRs were observed in patients with decompensated cirrhosis. CONCLUSIONS: Frailty was an independent predictor of cirrhosis progression or death and unplanned hospitalization across patients with compensated and decompensated cirrhosis. Future studies are needed to evaluate the possibility of slowing cirrhosis disease progression by reversing or preventing frailty.

Effects of community-based frailty-preventing intervention on all-cause and cause-specific functional disability in older adults living in rural Japan: A propensity score analysis.

Preventing frailty is crucial in aging societies. We examined the effectiveness of a community-based frailty-prevention program for delaying the onset of functional disability among community-dwelling older adults. From 2014 to 2019, 48 community-based frailty prevention classes (FPC, 60 min/session, once a week), comprising resistance exercise and nutritional or psychosocial programs, were established in Yabu City, Japan. We conducted a baseline survey in 2012 and followed up with participants for up to 6.8 years (4.8 years from establishing the first FPC). We analyzed data from 3350 older people. The primary and secondary outcomes were the onset of functional disability and cause-specific functional disability (including dementia and cardiovascular and orthopedic diseases), respectively. In addition to crude Cox proportional hazard regression, inverse probability of treatment weighting (IPTW) and propensity score matching (PSM; 918 nonparticipants and 459 participants) were used to adjust for confounders. Participants were more likely to be female and have a healthy lifestyle than nonparticipants. During the follow-up, 690 individuals developed a functional disability. The hazard ratio of incident functional disability in the participants was significantly lower than that in nonparticipants in the IPTW (hazard ratio 0.53, 95% confidential interval 0.38-0.75) and PSM (0.52, 0.37-0.71) analyses. In age-stratified analysis, significant associations were observed only in the ≥75-year-old subgroup. In a cause-specific analysis, participation significantly and consistently reduced incident functional disability caused by dementia (IPTW 0.47, 0.25-0.86; PSM 0.45, 0.25-0.83). Community-based FPC may be effective for preventing functional disability, especially caused by dementia, in this population.

Physical frailty, adherence to ideal cardiovascular health and risk of cardiovascular disease: a prospective cohort study.

BACKGROUND: longitudinal evidence concerning frailty phenotype and the risk of cardiovascular disease (CVD) remained insufficient, and whether CVD preventive strategies exert low CVD risk on frail adults is unclear. OBJECTIVES: we aimed to prospectively evaluate the association of frailty phenotype, adherence to ideal cardiovascular health (CVH) and their joint associations with the risk of CVD. METHODS: a total of 314,093 participants from the UK Biobank were included. Frailty phenotype was assessed according to the five criteria of Fried et al.: weight loss, exhaustion, low physical activity, slow gait speed and low grip strength. CVH included four core health behaviours (smoking, physical activity and diet) and three health factors (weight, cholesterol, blood pressure and glycaemic control). The outcome of interest was incident CVD, including coronary heart disease, heart failure and stroke. RESULTS: compared with the non-frail people whose incident rate of overall CVD was 6.54 per 1,000 person-years, the absolute rate difference per 1,000 person-years was 1.67 (95% confidence interval, CI: 1.33, 2.02) for pre-frail and 5.00 (95% CI: 4.03, 5.97) for frail. The ideal CVH was significantly associated with a lower risk of all CVD outcomes. For the joint association of frailty and CVH level with incident CVD, the highest risk was observed among frailty accompanied by poor CVH with an HR of 2.92 (95% CI: 2.68, 3.18). CONCLUSIONS: our findings indicate that physical frailty is associated with CVD incidence. Improving CVH was significantly associated with a considerable decrease in CVD risk, and such cardiovascular benefits remain for the frailty population.

Exercise to Prevent and Manage Frailty and Fragility Fractures.

PURPOSE OF REVIEW: This review identifies exercise-based recommendations to prevent and manage frailty and fragility fractures from current clinical practice guidelines. We also critically assess recently published literature in relation to exercise interventions to mitigate frailty and fragility fractures. RECENT FINDINGS: Most guidelines presented similar recommendations that included the prescription of individually tailored, multicomponent exercise programs, discouragement of prolonged sitting and inactivity, and combining exercise with optimal nutrition. To target frailty, guidelines recommend supervised progressive resistance training (PRT). For osteoporosis and fragility fractures, exercise should include weight-bearing impact activities and PRT to target bone mineral density (BMD) at the hip and spine, and also incorporate balance and mobility training, posture exercises, and functional exercise relevant to activities of daily living to reduce falls risk. Walking as a singular intervention has limited benefits for frailty and fragility fracture prevention and management. Current evidence-based clinical practice guidelines for frailty, osteoporosis, and fracture prevention recommend a multifaceted and targeted approach to optimise muscle mass, strength, power, and functional mobility as well as BMD.

Frailty: Pathophysiology, Theoretical and Operational Definition(s), Impact, Prevalence, Management and Prevention, in an Increasingly Economically Developed and Ageing World.

The world's population is ageing, and most older adults experience a later life burdened with disease and disability. Frailty is a multidimensional and dynamic condition characterized by declines in reserve and function across multiple physiological systems, such that the ability to cope with every day or acute stressors becomes compromised. It is projected to become one of the most serious public health challenges economically developed societies will face in the coming century. This review provides a comprehensive overview of frailty, exploring its pathophysiology, theoretical and operational definition(s), impact, prevalence, management, and prevention, within the context of its emergence as a major public health challenge, in an increasingly economically developed and ageing world. Further, this review discusses the major limitations, deficiencies, and knowledge gaps presently within the field, and future research directions pertinent to the advancement of frailty research and the promotion of healthy longevity among the increasing global population of older adults.