Development Of Physical Frailty Research Articles

Metabolic dysfunction and the development of physical frailty: an aging war of attrition.

The World Health Organization recently declared 2021-2030 the decade of healthy aging. Such emphasis on healthy aging requires an understanding of the biologic challenges aging populations face. Physical frailty is a syndrome of vulnerability that puts a subset of older adults at high risk for adverse health outcomes including functional and cognitive decline, falls, hospitalization, and mortality. The physiology driving physical frailty is complex with age-related biological changes, dysregulated stress response systems, chronic inflammatory pathway activation, and altered energy metabolism all likely contributing. Indeed, a series of recent studies suggests circulating metabolomic distinctions can be made between frail and non-frail older adults. For example, marked restrictions on glycolytic and mitochondrial energy production have been independently observed in frail older adults and collectively appear to yield a reliance on the highly fatigable ATP-phosphocreatine (PCr) energy system. Further, there is evidence that age-associated impairments in the primary ATP generating systems (glycolysis, TCA cycle, electron transport) yield cumulative deficits and fail to adequately support the ATP-PCr system. This in turn may acutely contribute to several major components of the physical frailty phenotype including muscular fatigue, weakness, slow walking speed and, over time, result in low physical activity and accelerate reductions in lean body mass. This review describes specific age-associated metabolic declines and how they can collectively lead to metabolic inflexibility, ATP-PCr reliance, and the development of physical frailty. Further investigation remains necessary to understand the etiology of age-associated metabolic deficits and develop targeted preventive strategies that maintain robust metabolic health in older adults.

A longitudinal study of factors associated with cognitive frailty in middle-aged and elderly population based on the health ecology model

BackgroundCognitive frailty (CF) is an important geriatric syndrome and is reversible. It is crucial to develop preventive interventions for CF. We aimed to explore the associations between CF and its associated factors in Chinese aged 45 years and above. MethodsBased on the available data of 3 waves in China Health and Retirement Longitudinal Study from 2011 to 2015, 16,071 individuals aged 45 years and above from 3 waves were included. Based on the health ecology model, the associated factors were classified as downstream, midstream and upstream factors. Generalized hierarchical linear model including time level, individual level, and province level was applied to analyze the associations between factors and CF. ResultsMultilevel factors have different effects on physical and cognitive function. In the downstream, old age, female, underweight, chronic diseases, and depression were risk factors of reversible CF and potentially reversible CF, and overweight was their protective factor. In the midstream, short or long night sleep duration was their risk factor, and > 30 and ≤ 60 min afternoon naps, alcohol drinking, and participation in social activities were their protective factors. In the upstream, living in rural areas was their risk factor, and high educational level, household consumption and GDP per capita were their protective factors. ConclusionsPhysical function and cognitive function are affected differently by multiple factors. The occurrence and development of physical frailty and cognitive impairment may have some common mechanisms. CF can be influenced by multilevel factors, and multilevel and comprehensive management of CF should be achieved. Key pointsCognitive frailty was correlated with multilevel factors, including downstream, midstream, and upstream factors.It is crucial to focus on individual interventions such as physiological factors, psychological factors and health behaviors, especially the elderly, women and those with depression.Socioeconomic status was associated with the lower prevalence of cognitive frailty.

Dietary factors in relation to the risk of cognitive impairment and physical frailty in Chinese older adults: a prospective cohort study.

The study aimed to investigate the independent associations of dietary factors with cognitive impairment (CI) and physical frailty (PF) among Chinese older adults. This study included 10,734 participants (mean age = 78.7years) free of CI and PF at baseline from the Chinese Longitudinal Health Longevity Survey. Dietary intake was collected using a simplified food frequency questionnaire every 3-4years. The Chinese version Mini-Mental State Examination was used to assess cognition function, participants with a score below 18 were defined as CI. PF was defined using the activities of daily living, instrumental activities of daily living, and functional limitation-related questions. The outcome was defined as the first onset of either CI or PF. Competing risk models were used to estimate the corresponding hazard ratios (HRs) and the 95% confidence intervals (95% CIs). During the study follow-up (mean = 8.1years), a total of 1220 CI cases and 1451 PF cases were newly identified. Higher frequency of fruits intake was associated with a lower hazard of CI (HR = 0.75, 95% CI 0.58-0.97), whereas higher intake of preserved vegetables demonstrated an opposite association (HR = 1.23, 95% CI 1.07-1.42). In terms of PF, we observed a lower risk associated with higher meat and poultry intake (HR = 0.72, 95% CI 0.61-0.88). In particular, a significant protective association of fish and aquatic products intake with PF was observed among participants with ≥ 28 natural teeth (HR = 0.52, 95% CI 0.27-0.99). Our findings suggest divergent roles of major dietary factors in the development of CI and PF among Chinese older adults.

Relationship between the spread of coronavirus disease 2019, social frailty and depressive symptoms in patients with heart failure

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): the Japan Society for the Promotion of Science (JSPS) KAKENHI Background Owing to the spread of coronavirus disease 2019 (COVID-19), people have refrained from going out unnecessarily and have been maintaining social distance. These new lifestyle approaches have affected people physically, psychologically, and socially. Patients with heart failure (HF) are more likely to have social frailty, physical frailty, cognitive impairment, and depressive symptoms, and an overlap of these conditions leads to adverse events. Therefore, multi-domain assessment and understanding of the condition of patients with HF are important for disease management. The spread of COVID-19 is a predicted risk factor for these events, but its impact in patients with HF has not been investigated. Purpose We investigated whether the spread of COVID-19 is associated with the development of the multi-domain of frailty in patients with HF. Methods Patients who were independent in their daily activities before admission were included in the study. The presence of social frailty (Makizako’s five items), physical frailty (Fried phenotype model), cognitive impairment (Mini-Cog), and depressive symptoms (the Patient Health Questionnaire-2) in patients with HF were assessed at hospital discharge. Logistic regression analyses were used to examine the impact of the spread of COVID-19 on the development of the multi-domain of frailty in patients with HF. Results We included 482 patients in this study. Median patient age was 74 years, and 64.5% were male. In multivariate logistic regression analyses, the spread of COVID-19 was significantly associated with the development of social frailty (odds ratio [OR]: 1.15, 95% confidence interval [CI]: 1.02–1.30) and depressive symptoms (OR: 1.14, 95% CI: 1.02–1.27) but not with the development of physical frailty (OR: 1.24, 95% CI: 0.51–3.02) and cognitive impairment (OR: 1.72, 95% CI: 0.80–3.73). Conclusion The spread of COVID-19 was associated with the development of social frailty and depressive symptoms in patients with HF. Evaluation of social frailty and depressive symptoms during hospitalization would support disease management and understand their social and psychological conditions specific to the spread of COVID-19.

Multisystem derangements in frailty and sarcopenia: a source for biomarker discovery.

Multisystem derangements, encompassing metabolic, musculoskeletal and stress-response systems, occur during aging and are associated with the development of physical frailty and sarcopenia. These modular changes are relevant sources for the identification of biomarkers for the two conditions. Here, we provide an up-to-date overview on existing biomarkers of physical frailty and sarcopenia and discuss emerging approaches for biomarker discovery. Inflammatory, metabolic and hematologic markers are shared between physical frailty and sarcopenia. Gut microbial derivatives and damage-associated molecular patterns transferred via extracellular vesicles have been indicated as possible gut-muscle axis regulators and candidate markers of physical frailty and sarcopenia. Mediators of metabolic, musculoskeletal and stress-response system dysregulation are shared by physical frailty and sarcopenia and indicate the existence of common pathophysiological pathways. Multiplatform biomarker analyses have been proposed as an innovating approach for tracking the multifaceted and dynamic nature of physical frailty and sarcopenia. Upon validation, the identified biomarkers may support diagnostic makeup and tracking of the two conditions in both research and clinical settings.

Effect of social participation on the development of physical frailty: Do type, frequency and diversity matter?

BackgroundLittle is known about the longitudinal association between social participation and incident frailty in community-dwelling older adults in general and particularly in China. This study examined the impact of type, frequency and diversity of social participation on incident physical frailty at two-year follow-up. MethodLongitudinal data from three waves of the China Health and Retirement Longitudinal Study were used. Older adults who were non-frail and aged 60 years or more at baseline and had information on physical frailty at follow-up were included. Frailty was measured using the modified frailty phenotype criteria. Social participation was measured as the type, frequency and diversity of engagement in social activities, including interacting with friends, playing group games, participating in sports clubs, community-related organizations, and voluntary activities. ResultsA total of 6959 eligible respondents were included. Playing group games (OR=0.73, 95%CI=0.55–0.96) or participating in the activities of sports clubs (OR=0.54, 95%CI=0.34–0.85) once or more times per week led to a decreased risk of developing frailty in two years whereas participating in voluntary activities occasionally (OR=0.50, 95%CI=0.30–0.84) had a protective effect on the development of frailty. More diverse social participation was significantly associated with lower risk of incident frailty at two-year follow-up. ConclusionsThe association between social participation and onset of physical frailty differed by the specific type and frequency of the activities that older adults engaged in. Promoting social participation of various types and at an appropriate frequency may be a promising way to mitigate the burden associated with physical frailty among older adults.

Dietary factors associated with the development of physical frailty in community-dwelling older adults.

Nutrition plays an important role in the development of frailty, and the present study examined the association between energy, macronutrient, and food intake and the development of physical frailty. Prospective cohort study. The National Institute for Longevity Sciences - Longitudinal Study of Aging (NILS-LSA), a community-based study. Participants included 166 men and 117 women aged 65-86 years without frailty components at baseline who participated in both the sixth (2008-2010) and seventh (2010-2012) waves of the NILS-LSA. Physical frailty was assessed using the modified criteria established by the Cardiovascular Health Study (2001). All participants were classified as "robust (number of frailty components: 0)," "prefrail (1-2)," or "frail (3-5)." Energy, macronutrient, and food intake was calculated based on 3-day dietary records during the sixth wave. Associations between dietary intake per day and the development of frailty 2 years later (from robust at the sixth wave to prefrail/frail at the seventh wave) were examined using multiple logistic regression analysis after adjusting for sex, baseline age, and other covariables. Among the participants included, 36% were classified as prefrail/frail 2 years later. Higher energy [1 standard deviation (SD), odds ratio (95% confidence interval): 362 kcal, 0.68 (0.49-0.94)], protein [16 g, 0.72 (0.53-0.97)], and fat [15 g, 0.69 (0.52-0.92)] intake was negatively associated with frailty development. Higher meat [38 g, 0.68 (0.51-0.92)] and dairy [114 g, 0.73 (0.55-0.96)] intake was negatively associated with frailty development. Higher energy intake was negatively associated with the development of weakness (low grip strength) and low activity, while higher protein intake was negatively associated with the development of low activity. Increased consumption of meat and dairy products may provide sufficient protein and fat necessary for achieving higher energy intake, thereby effectively preventing physical frailty among older Japanese individuals.

Specific Profiles Of Circulating Mediators Characterize Older Persons With Physical Frailty And Sarcopenia

Chronic inflammation, changes in body composition, muscle loss (sarcopenia) and decreasing homeostatic reserve (frailty) are hallmarks of aging. Several circulating inflammatory markers have been associated with these age‐related conditions. However, a gold standard biomarker able to predict functional impairment in older adults is currently unavailable. Muscle is crucial for several metabolic processes, including protein/aminoacid metabolism. Perturbations in protein/aminoacid metabolism may play also a role in the development of physical frailty and sarcopenia (PF&S). The simultaneous analysis of an array of circulating aminoacid/metabolites and their relationship with inflammatory mediators may help gain insights in the pathophysiology of PF&S.To this aim, we analyzed the profile of circulating inflammatory mediators and amino acids in older people with and without PF&S.More than five hundred persons aged 70+ years were screened. Of these, sixty (20 men and 40 women; mean age 76.9±4.8 years) were diagnosed with PF&S. Thirty (14 men and 16 women) non‐sarcopenic, non‐frail persons were enrolled in the control group. A panel of 27 cytokines, chemokines and growth factors was analyzed via a multiplex, magnetic bead‐based immunoassay on a Bio‐Plex® System with Luminex xMap Technology. A panel of 37 serum amino acids and derivatives was assessed by UPLC‐MS. Multi‐block partial least squares discriminant analysis (PLS‐DA) was employed to explore the relationship among inflammatory and amino acid profiles of people with PF&S. Double cross‐validation procedures were used to validate the predictive ability of the PLS‐DA model.The optimal complexity of the PLS‐DA model was found to be three latent variables. The proportion of correct classification was 85.5 ± 4.4 for persons with PF&S and 88.3 ± 3.6 for controls. As for the amino acid profile, people with PF&S showed higher levels of aspartic acid, asparagine, taurine, citrulline, alpha‐aminobutyric acid, methionine, and glutamic acid. Increased levels of interleukin‐8, myeloperoxidase, and platelet derived growth factor‐BB were also found in people with PF&S.The dissection of these patterns may provide novel insights into the role played by inflammatory mediators and protein/amino acid perturbations in the disabling cascade associated with PF&S and possible new targets for interventions.Support or Funding InformationThis study was supported by the “Centro Studi Achille e Linda Lorenzon”, intramural research grants from the Catholic University of the Sacred Heart (D3.2 2013 and D3.2 2015), Innovative Medicines Initiative Joint Undertaking (IMI‐JU 115621), and Fondazione Roma (NCDs Call for Proposal 2013)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Operationalization of the physical frailty & sarcopenia syndrome: rationale and clinical implementation.

Over the years, different operational definitions have been elaborated to identify frail older persons, but none of them has received unanimous consensus. This, in turn, has hampered the clinical implementation of frailty as well as the design of targeted interventions. To overcome the current limitations in the field, a novel operationalization of physical frailty (PF) is proposed which grounds its roots in the recognition of sarcopenia as its central biological substrate. This conceptualization is based on the fact that the clinical picture of PF overlaps substantially with that of sarcopenia. The two conditions may therefore be merged into a new clinical entity, the PF & sarcopenia (PF&S) syndrome, in which muscle loss represents both the biological substrate for the development of PF and a major pathway whereby the negative health outcomes of PF occur. All of the components defining the PF&S syndrome are measurable in an objective manner, which will facilitate its incorporation into standard practice. The recognition of a precise biological substratum for PF&S (i.e., skeletal muscle decline) also opens new venues for the development of preventive and therapeutic interventions.

Cognitive aspects of frailty: mechanisms behind the link between frailty and cognitive impairment.

Whereas physical impairment is the main hallmark of frailty, evidence suggests that other dimensions, such as psychological, cognitive and social factors also contribute to this multidimensional condition. Cognition is now considered a relevant domain of frailty. Cognitive and physical frailty interact: cognitive problems and dementia are more prevalent in physically frail individuals, and those with cognitive impairment are more prone to become frail. Disentangling the relationship between cognition and frailty may lead to new intervention strategies for the prevention and treatment of both conditions. Both frailty and cognitive decline share common potential mechanisms. This review examines the relationship between frailty and cognitive decline and explores the role of vascular changes, hormones, vitamin D, inflammation, insulin resistance, and nutrition in the development of physical frailty and cognitive problems, as potential underlying mechanisms behind this link. Dual tasking studies may be a useful way to explore and understand the relation between cognitive and physical frailty. Further studies are needed to elucidate this complex relation to improve the outcomes of frailty.

Psychological well-being and incident frailty in men and women: the English Longitudinal Study of Ageing

Observations that older people who enjoy life more tend to live longer suggest that psychological well-being may be a potential resource for healthier ageing. We investigated whether psychological well-being was associated with incidence of physical frailty. We used multinomial logistic regression to examine the prospective relationship between psychological well-being, assessed using the CASP-19, a questionnaire that assesses perceptions of control, autonomy, self-realization and pleasure, and incidence of physical frailty or pre-frailty, defined according to the Fried criteria (unintentional weight loss, weakness, self-reported exhaustion, slow walking speed and low physical activity), in 2557 men and women aged 60 to ≥ 90 years from the English Longitudinal Study of Ageing (ELSA). Men and women with higher levels of psychological well-being were less likely to become frail over the 4-year follow-up period. For a standard deviation higher score in psychological well-being at baseline, the relative risk ratio (RR) for incident frailty, adjusted for age, sex and baseline frailty status, was 0.46 [95% confidence interval (CI) 0.40-0.54]. There was a significant association between psychological well-being and risk of pre-frailty (RR 0.69, 95% CI 0.63-0.77). Examination of scores for hedonic (pleasure) and eudaimonic (control, autonomy and self-realization) well-being showed that higher scores on both were associated with decreased risk. Associations were partially attenuated by further adjustment for other potential confounding factors but persisted. Incidence of pre-frailty or frailty was associated with a decline in well-being, suggesting that the relationship is bidirectional. Maintaining a stronger sense of psychological well-being in later life may protect against the development of physical frailty. Future research needs to establish the mechanisms underlying these findings.

Assessment of biomarkers of protein anabolism in skeletal muscle during the life span of the rat: sarcopenia despite elevated protein synthesis.

Loss of muscle strength is a principal factor in the development of physical frailty, a condition clinically associated with increased risk of bone fractures, impairments in the activities of daily living, and loss of independence in older humans. A primary determinant in the decline in muscle strength that occurs during aging is a loss of muscle mass, which could occur through a reduction in the rate of protein synthesis, an elevation in protein degradation, or a combination of both. In the present study, rates of protein synthesis and the relative expression and function of various biomarkers involved in the initiation of mRNA translation in skeletal muscle were examined at different times throughout the life span of the rat. It was found that between 1 and 6 mo of age, body weight increased fourfold. However, by 6 mo, gastrocnemius protein synthesis and RNA content per gram of muscle were lower than values observed in 1-mo-old rats. Moreover, the relative expression of two proteins involved in the binding of initiator methionyl-tRNA to the 40S ribosomal subunit, eukaryotic initiation factors (eIF)2 and eIF2B, as well as the 70-kDa ribosomal protein S6 kinase, S6K1, was lower at 6 mo compared with 1 mo of age. Muscle mass, protein synthesis, and the aforementioned biomarkers remained unchanged until approximately 21 mo. Between 21 and 24 mo of age, muscle mass decreased precipitously. Surprisingly, during this period protein synthesis, relative RNA content, eIF2B activity, relative eIF2 expression, and S6K1 phosphorylation all increased. The results are consistent with a model wherein protein synthesis is enhanced during aging in a futile attempt to maintain muscle mass.

Fear-related avoidance of activities, falls and physical frailty. A prospective community-based cohort study.

to investigate the relationship between fear-related avoidance of activities and physical frailty. fear-related avoidance of activities, physical performance, maximal isometric muscle strength and postural control were assessed in 225 community-living elderly (94 men and 131 women), aged between 61 and 92 years of age. bivariate analyses revealed significant correlations between avoidance of activities on the one hand, and physical performance, muscle strength, forward endpoint excursion of the centre of gravity, and previous falls on the other hand. Logistic regression analysis revealed that fear of falling and avoidance of activities in daily life were predictive of falls within a 1-year follow-up, together with general fear of falling, old age and being female. fear-related avoidance of activities may have negative effects on physical abilities and may also be predictive for future falls. Avoidance of activities is therefore an important additional psychological variable in the development of physical frailty and falling in community-living elderly.