Symposia
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PubMed Central (PMC)
J Frailty Aging. 2020; 9(Suppl 1): 1–45.

PMCID: PMC7223136

PMID: 32150216

Symposia

Copyright © Serdi and Springer Nature Switzerland AG 2020

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Symposia

S1- THE SPRING STUDY: CHARACTERIZING RESILIENCE AND FRAILTY TO PHYSICAL STRESSORS USING A DYNAMICAL PHYSIOLOGICAL SYSTEMS APPROACH. Karen Bandeen-Roche (Johns Hopkins University, Baltimore, USA)

Communication 1:The Measurement of Physical Resiliencies: Conceptualization and Study Design, Karen Bandeen-Roche (Johns Hopkins University, Baltimore, USA)

We aim to develop signatures of physical resilience in older adults who will undergo clinical stressors; validate the signatures’ ability to distinguish those who will, or not, respond resiliently, and characterize underlying physio-biological determinants. This presentation describes the study conceptualization and design. The underlying physiology is conceptualized as a dynamical system, and resilience, as a property thereof. A pilot/confirmatory study has been initiated with branches addressing three clinical stressors. Resilience signatures will be grounded in dynamical data from multiple stress-response assessments; many other markers are being collected. We propose a data analytic strategy to build signatures, and evaluate their success predicting both short-and long-term responses to stressors, with both data- and theory-driven elements. If successful, our study will generate new means to identify individuals with impaired resiliency to stressors, deepen knowledge of age-related biological changes that impair stress-response, and open the way for novel interventions to bolster resiliency.

Communication 2:Physical Resiliencies in Three Major Clinical Stressors, Jeremy Walston (Geriatric Medicine and Gerontology, Johns Hopkins University, Baltimore, USA)

To study resiliencies among older adults, we designed and are implementing pilot projects in three clinical stressors: total knee replacement surgery (TKR); initiation of hemodialysis; and bone marrow transplantation (BMT) in hematologic malignancies. Each study aims to characterize signatures of resiliency in older adults by gathering extensive measurements before, during and after a stressor. For each stressor, we present rationale for stressor selection, considerations for conceptualizing resilience, study design and progress, and challenges encountered in the research. Re-attainment of baseline physical function or improvement over baseline function (as in TKR) is a shared resiliency response whereas resolution of pain, post-dialysis recovery time, and immune recovery exemplify responses specific to the respective stressors. Challenges include uncertainty in hemodialysis initiation timing and BMT eligibility. Each stressor is increasingly prevalent in older adults and elicits heterogeneous responses. The development of resiliency signatures may allow targeted interventions before stressor onset.

Communication 3:Do Dynamical System Measures at Baseline Predict Responses to Clinical Stressors? Findings from Pilot Studies of Physical Resilience and Aging, Ravi Varadhan (Oncology Biostatistics, Johns Hopkins University, Baltimore, USA)

Resilience of an organism is essentially a dynamic property. Hence, in order to characterize the resilience of an organism, it is essential to perturb it and study its response. In the Study of Physical Resilience and Aging (SPRING), we are assessing anumber of dynamical responses at baseline. These include response of cardiac autonomic nervous system using Holtermonitoring, oral glucose tolerance test, 24-hour diurnal cortisol response, fatigability to treadmill test, and ACTH stimulation test. We have collected pilot data in 58 subjects undergoing 3 clinical stressors. The data will be analyzed using a dynamical systems modeling framework that we have developed. Our preliminary results show that the stimulus-response data from multiple dynamic systems can be parsimoniously characterized using two principal components, which reflect overall and adaptive homeostatic regulation. We will evaluate how these two measures of resiliency predict the recovery of physical, cognitive, and clinical trajectories. We will present the preliminary findings from these dynamic responses in three different clinical stressors: bone-marrow transplantation in hematologic malignancies, hemodialysis initiation in end-stage renal disease, and total knee replacement.

S2- SARCOPENIA AND NEUROSCIENCE: A FAILURE TO COMMUNICATE. Stephen B. Kritchevsky (Sticht Center for Healthy Aging and Alzheimer’s Prevention, Wake Forest School of Medicine, Winston Salem, USA)

Communication 1:Welcome and Introductory Comments, Stephen B. Kritchevsky (Sticht Center for Healthy Aging and Alzheimer’s Prevention, Wake Forest School of Medicine, Winston Salem, USA)

Professor Kritchevsky will introduce the symposium. His introductory comments will focus on the clinical significance of both muscle strength and gait speed having predictive power in relation to a range of health conditions — even when these are assessed decades later — has motivated claims that they can serve as a «vital signs» for middle-aged and older adults.

Communication 2:Sarcopenia — Dynapenia: Reflecting back on the last decade, Brian C. Clark (Ohio Musculoskeletal and Neurological Institute (OMNI), Ohio University, Athens, USA)

Professor Clark will introduce the premise that strength is a simple measure of physical performance that provides a marker of skeletal muscle status in general, and sarcopenia in particular. He will then present recent data and analyses arguing that central neural mechanisms are a, if not the, critical determinant of the age-related loss of muscle strength as well as mobility. Here, he will provide an overview of the concept of dynapenia (age-related loss of muscle strength) highlighting key findings suggesting that dynapenia and the age-related loss of muscle mass, which was originally defined as sarcopenia, are not as mechanistically linked as originally believed. In this context, he will discuss the evolution of the definition of sarcopenia over the past decade, and present new data illustrating that older adults with clinically-meaningful leg extensor muscle weakness exhibit impairments in their central neural activation capacity of muscle and corticospinal hypoexcitability. He will also present neuroimaging data examining the neural correlates of weakness and mobility.

Communication 3:Get a grip: individual variations in grip strength are a marker of brain health, Richard G. Carson (Trinity College Institute of Neuroscience & School of Psychology, Trinity College Dublin, Dublin, Ireland)

Professor Carson will argue that the application of grip force is a complex coordinated behavior that is mediated by integrated activity across distributed brain networks, with individual variations in the capacity to generate grip force being closely associated with a broad spectrum of markers that reflect brain health. Collectively, this symposium will highlight the convergent functional and structural mediation of cognitive and motor processes by the brain. Accordingly, the origins of the close and pervasive relationships between age- related declines in maximum grip strength and expressions of cognitive dysfunction will be readily appreciated. The overriding conclusion arising from the analyses that will be presented is that maximum strength testing provides a discriminating measure of neurological function. The ramifications are clear. To the extent that changes in maximum strength can be registered over relatively short periods, they have the potential to serve as early markers of incipient changes in brain health. In presaging the accumulation of deficits that will ultimately impact negatively not only on cognitive status but also give rise to manifestations of frailty, loss of functional independence, and reduced quality of life, the monitoring of strength may assist in prognosis and facilitate early intervention. With respect to various conditions of aging, including those to which the designations sarcopenia or frailty have been applied, the implications of this symposium will extend beyond our understanding of etiology. They also bear prominently upon the design and deployment of therapeutic interventions geared to combat these conditions. It is not unusual to read statements along the lines of “sarcopenia is the major cause of frailty”. Although the basis for such conclusions is typically evidence (e.g., statistical associations with expressions of frailty) derived using consensus classifications of “sarcopenia” that include indices of “muscle function” (maximum grip strength and/or walking speed), the associated discussion of causal relations is often restricted entirely to the molecular and cellular physiology of skeletal muscle. While in any domain of research there will be a range of emphases that emerge in the interpretation of empirical findings, there is presently a wide spread and striking disconnect between the multifactorial measures that are used to assess “sarcopenia” and the rather uniform prescriptions that issue forth. The latter are in many instances predicated upon an interpretation of the “muscle function” dimension of “sarcopenia”determinations that excludes entirely the contributory role of the central nervous system. This uniformity of emphasis is reflected in the pharmacological approaches being developed, or currently available, with the goal of treating “sarcopenia”. These include vitamin D, protein (essential amino acids), testosterone, selective androgen receptor modulators, growth hormone, ghrelin agonists, myostatin inhibitors, activin 11R antagonists, angiotensin- converting enzyme inhibitor (perindopril), espindolol (B1/B2 adrenergic receptor antagonist), and fast skeletal muscle troponin activators. Although the respective efficacy of these treatments is a matter for empirical enquiry, it is clear that the assumed nature of the underlying pathophysiology does not in most cases extend to the brain. Why is this of practical concern? The achievement of a useful endpoint in phase II trials of such treatments may be defined in terms of some measure of muscle mass or muscle quality (i.e., consistent with the presumed mechanism of action of most of the pharmacological agents listed previously). This may however prove to be entirely irrelevant if a consensus definition of “sarcopenia” is used to judge efficacy in phase III clinical trials. The data and analyses to be presented in this symposium will illustrate that tests of maximum strength (as well as gait sufficiency) —the elements of the current consensus definitions of “sarcopenia” that have the greatest predictive power in relation to functional status — reflect primarily the integrity of the brain. Stated directly, a case will be made that the steps that are being taken presently to address a perceived deficiency in muscle mass or muscle quality are quite distinct from those actually mandated by what are evidently deficits in neuromuscular control.

S3- PRIMARY CARE APPROACH TO GERIATRIC ASSESSMENT, FRAILTY AND SARCOPENIA. John Morley (Division of Geriatric Medicine, Saint Louis University School of Medicine, Saint Louis, USA)

Communication 1:Primary Care approach to frailty and sarcopenia, Jean Woo (The Chinese University of Hong Kong, Hong Kong)

There exists unmet needs in ageing populations that require to be addressed using integrated health and social care systems in the primary care setting. Problems commonly encountered include poor oral health, problems with hearing and vision, physical and cognitive frailty, poor psychological wellbeing, dependency in instrumental activities of daily living, problems with medication and polypharmacy, problems with finance and care, all of which promote increase use of hospital services. This presentation describes a step care model involving community centres in all 18 districts of Hong Kong, using automated means to carry out geriatric screening as well as blood pressure measurements, followed by protocols for dealing with identified problems. Data are transferred to cloud for analysis and generation of individual reports. Subsequent action may include one on one consultation with a nurse or social worker, or group activities. Only if necessary will the older person be directed to a medical clinic for further management. The commonest unmet needs were memory complaints (>70%); frailty and pre-frailty (>60%), chewing difficulties (38%); Problems with IADL; polypharmacy (24%); and a feeling of life having no meaning (22%). Exercise programs for sarcopenia improve strength, physical function and activities of daily living that lasted 12 weeks beyond the cessation of exercise program, while addition of a nutrition supplement containing HMB has incremental effect on muscle mass but not function, only during the period of supplementation. A multi-component frailty prevention program also reverses frailty and improves physical and cognitive functions as well as self-rated health among those who were pre-frail. Opportunities exist in the primary care setting to address unmet needs of older people by detection of geriatric syndromes followed by community-based intervention programs. A medico social model could represent the first step in a step care approach that can be linked to healthcare facilities with multidisciplinary health care professionals.

Communication 2:The Rapid Geriatric Assessment: a Tool for Primary Care Physicians, John Morley (Division of Geriatric Medicine, Saint Louis University School of Medicine, Saint Louis, USA)

The Rapid Geriatric Assessment screens for frailty (FRAIL), sarcopenia (SARC-F), anorexia of aging (SNAQ) and cognition (Rapid Cognitive Screen (RCS). All are validated in multiple continents. We will give an overview of its validation and on the results of its use in over 14,000 older persons in multiple clinical sites in Missouri. We will also show the results for components of FRAIL and it’s treatment algorithm.

Communication 3:The Utility of Rapid Geriatric Assessment App to Identify Unmet Needs of Older Adults in Primary Care, Reshma A Merchant (National University Health System of Singapore, Singapore)

With rapid increase in ageing population, especially in Asian countries and limited number of geriatricians, there is an immediate need to enhance ability of primary care physicians, coordinators and nurses to screen and manage geriatric syndromes. There is increasing emphasis on primary care in the 21st century to provide comprehensive, preventive and person-centered care plan, and are well positioned to succeed in population health. Frailty, Sarcopenia, cognitive impairment, falls, nutrition and loneliness are well known precursors of functional decline and disability. Rapid Geriatric Assessment (RGA) developed by Saint Louis University measures frailty, sarcopenia, anorexia and cognition. In addition to screening, the RGA also includes additional questions should a person screen positive eg for fatigue, to exclude depression, sleep apnoea and additional investigations to exclude hypothyroidism, B12 deficiency and management plans eg recommendations on exercise and vitamin D. RGA application (eRGA) is practical, fast and efficient app which can be used by coordinator and nurse in primary care. Frailty is measured using the FRAIL scale, sarcopenia using Sarc-F, nutrition using SNAQ (Simplified Nutritional Assessment Questionnaire) and cognition using the rapid cognitive screen. For those with fatigue, depression was measured using PHQ-9. More than 1/3 were either pre-frail or frail but 1/6 had difficulties with climbing 1 flight of stairs or walking 1 bus stop. More than 2/3 of those who complained of fatigue had underlying depression. Similarly, 1 in 6 were significantly at risk of having at least 5% of weight lost in 6 months. Using Sarc-F, 1 in 5 had underlying sarcopenia. eRGA app is a practical and feasible way to identify seniors at risk in primary care even before they develop disability. The RGA app identified relevant geriatric syndromes and with appropriate implementation pathway could lead to improved outcomes.

S4- NOVEL BIOMARKERS AT THE INTERSECTION OF FRAILTY AND ALZHEIMER’S DISEASE. Jeremy D. Walston (Johns Hopkins University, Baltimore, USA)

Communication 1:Nuclear factor-kappa B-mediated (NFκB) related inflammatory markers and cognitive impairment, Esther Oh (Johns Hopkins University, Baltimore, USA)

Inflammatory markers are well known to be associated with frailty and other comorbidities including cognitive impairment. Among inflammatory markers, nuclear factor-kappa B-mediated (NFκB) related markers have been known to be associated with aging and its associated adverse outcomes including mortality. Elevated levels of NFκB related inflammatory markers may also be associated with cognitive impairment. Inflammatory markers CRP, IL6, TNFR1, and TNFα were measured in the sera of the study participants from the Religious Orders Study and Rush Memory and Aging Project (N=659). All assays were performed on the Meso Scale Discovery (MSD) electrochemiluminescence platform. The most significant association was found with TNFR1 and composite global cognitive score with a 7.7 standard unit lower score per 1 log unit of higher TNFR1 (−7.7; 95% CI −10.55 to −4.84). TNFR1 was also associated with different domains of cognition including working memory (−0.31; 95% CI −0.47 to −0.15), episodic memory (−0.38; 95% CI −0.55 to −0.22), semantic memory (−0.41; 95% CI −0.56 to −0.25), perceptual speed (−0.50; 95% CI −0.68 to −0.32), and perceptual orientation (−0.23; 95%CI −0.39 to −0.08). CRP and IL-6 were both associated with perceptual speed, but TNFα was not associated with cognition. Higher levels of TNFR1, CRP, and IL6 are associated with cognitive function. Of these, only TNFR1 was associated with all five cognitive domains examined. We will also present data on the association of NFκB related markers and longitudinal cognitive changes as well as the association of inflammatory markers with circulating cell-free (ccf) DNA fragments that were measured in the same population.

Communication 2:Circulating cell-free DNA is associated with faster rates of cognitive decline and worsening physical measures over time, L. Nidadavolu (Johns Hopkins University, Baltimore, USA)

In tissue homeostasis, damaged and dysfunctional cells die, releasing DNA fragments into circulation. Circulating cell-free (ccf) DNA fragments come from two sources: nucleus (ccf-nDNA) and mitochondria (ccf-mtDNA). The quantity of ccf-nDNA serves as a marker of total cell death, while the size and relative abundance of ccf-mtDNA fragments can be utilized to distinguish mechanism of cell death. The utility of ccf-DNA fragments in identifying and predicting progression of patients at high risk for frailty and Alzheimer’s disease is currently unknown. Profiling of genomic and mitochondrial (short, intermediate and long) ccf-DNA was performed in sera of older individuals from Rush University Alzheimer Disease Center’s Religious Orders Study/Memory and Aging Project (median age 80.4 years, N=670). Ccf-DNA levels were correlated with physical and cognitive performance scores including walking speed, grip strength, frailty score as well as composite cognitive testing scores. Associations with trajectories of physical and cognitive decline as well as other molecular measures including serum cytokines were also determined. Ccf-nDNA was negatively correlated with minimental status exam (MMSE) score (r = −0.112, p = 0.005), overall global cognition (r = −0.102, p = 0.01) and gait speed (r = −0.116, p =0.01). Longitudinal analysis showed baseline increases in ccf-nDNA resulted in decreased global cognition score of 0.11 per year and a decrease in grip strength of 0.2 units per year. Higher levels of short ccf-mtDNA fragments normalized per cell was also associated with increased mortality (hazard ratio fordeath = 1.11). Mitochondrial dysfunction and cellular senescence constitute primary theories of aging and are commonage-related changes seen in patients with physical and cognitive decline. Our data highlights the utility of ccf-DNA fragments inidentifying and risk stratifying older patients at high risk for frailty and AD.

Communication 3:Angiotensin system and the intersection of frailty and Alzheimer’s disease, P. Abadir (Johns Hopkins University, Baltimore, USA)

Chronic inflammation commonly accompanies frailty and increases risk of cognitive decline and the progression of AD. The Renin-Angiotensin-System (RAS) is a major hormonal system that affects every organ and mainly functions through three receptor subtypes; AT1R, AT2R and the brain-specific AT4R. The role of RAS at the intersection of frailty and Alzheimer’s disease is currently controversial. Frailty status, grip strength, walking speed, falls, and mortality in community-dwelling younger (age 20–30, N=39), and older individuals (age 70–90, N=63) were correlated to serum levels of angiotensin autoantibodies (AT1RaAb) and to serum cytokines. Brain frontal cortex AT1R, AT2R and AT4R gene expression, protein synthesis, and signaling pathways were also examined in a separate group of age- and sex-matched control and angiotensin receptor blocker treated (80–90Y) non-AD and AD subjects (The Rush Alzheimer’s Disease Center) (N=30 each group). Our data suggests that in older adults with normal cognition, higher serum levels of AT1RaAb were strongly associated with higher inflammation and frailty; the risk of all-cause mortality was 4 times higher than in those with lower AT1RaAb levels. This excess risk of death did not diminish after multiple adjustments. Angiotensin receptor blocker (ARB) treatment appeared to be most protective in these older adults with higher AT1RaAb serum levels. Similarly, at brain tissue level, in older subjects with AD there is an increase in the proinflammatory brain AT1 expression (P<0.01) and signaling (pERK) (p<0.008). The anti-inflammatory AT2R expression was also increased (P<0.003). However, AT2R signaling pathways (eNOS, nNOS) were not up-regulated, suggesting discordance between receptor expression and activity. Our findings highlight dysregulation of circulating and Brain RAS in patients with frailty and AD. Dissecting and understanding circulating and tissue specific RAS changes in frailty and AD is therefore critical for accurately targeting the impaired parts of the system.

S5- SCREENING AND ASSESSMENT FOR FRAILTY IN PRIMARY CARE. Solomon Yu (National Health and Medical Research Council Centre of Research Excellence in Frailty and Healthy Ageing, Adelaide, Australia)

Communication 1:Utilisation Of General Practice Health Assessments Around An Aged Care Assessment Is Associated With Lower Mortality Risk In Older Australians, R. Visvanathan (National Health and Medical Research Council Centre of Research Excellence in Frailty and Healthy Ageing, Adelaide, Australia)

The Medicare Benefits Schedule (MBS) supports an annual comprehensive assessment of older (75+) people by general practitioners through MBS item number 705/707 (45 minutes+). The aims of this study were to: 1) describe the utilisation of comprehensive assessments within 6 months of the national Aged Care Assessment Program (ACAP) assessment for home care packages (HCPs); and 2) investigate the impact of the comprehensive assessment item numbers on the risk of mortality and entry into permanent residential aged care (PRAC). Retrospective cohort study utilising the Historical Cohort of the Registry of Senior Australians (ROSA). 75,172 individuals >=75 years old having an eligibility assessment between 2011 and 2015 were investigated. The use of comprehensive assessments MBS items 705/707 in the six months before and after the eligibility assessment for HCP and impact on time to death and entry into PRAC were investigated. Of the 75,172 individuals, 28.2% (95% confidence interval (CI): 27.8–8.5%) had comprehensive assessments. Individuals with a comprehensive assessment had a 5% lower risk of mortality (adjusted hazard ratio (aHR, 95%CI=0.95,0.92–0.98), but 5% higher risk of transition to PRAC (aHR, 95%CI=1.05, 1.02–1.08) compared to those who did not have these services. The utilisation of comprehensive assessments was associated with a lower risk of mortality.

Communication 2:FRAIL Scale and SARC-F: Predictive Validity and Diagnostic Test Accuracy, M.Q. Thompson (National Health and Medical Research Council Centre of Research Excellence in Frailty and Healthy Ageing, Adelaide, Australia)

This study examined the predictive validity of the FRAIL scale and SARC-F to predict mortality, and their diagnostic test accuracy (DTA) against the respective reference standards of the frailty phenotype (FP) and sarcopenia. A total of 668 participants aged >=65 years (mean age 74.0 [SD 6.2] years, 56.1% female) were included. Frailty was measured using the FRAIL scale and FP, and Sarcopenia using SARC-F and clinical measurement. Mortality was matched to official death records with a minimum 10 years follow-up. DTA estimates considered as acceptable: Sensitivity >=80%, >=Specificity 60%, Youden index >=50%. Both instruments demonstrated significant predictive validity for mortality up to 10 years in an analysis adjusted for sex, age, education, and income (FRAIL scale. HR: 2.08, p < .001; and SARC-F. HR: 2.04, p < .001). The FRAIL scale demonstrated acceptable DTA findings against the FP for both Sensitivity (86.3%), Specificity (63.6%) and Youden index (49.9%), while the SARC-F did not produce acceptable estimates (Sensitivity: 78.2%, Specificity: 36.5, Youden: 14.7%). The FRAIL scale is a suitable frailty screening instrument. While the SARC-F did not produce acceptable DTA estimates, it did demonstrate predictive validity for mortality.

Communication 3:The Pictorial Fit-Frail Scale (PFFS) Malay Version: Validity and Reliability Testing in Malaysia, S.S. Ahip (National Health and Medical Research Council Centre of Research Excellence in Frailty and Healthy Ageing, Adelaide, Australia)

The aim was to investigate test-retest and inter-rater reliability as well as validity of the PFFS- Malay version (PFFS-M). 240 patients and their caregivers from 4 public primary healthcare clinic completed the PFFS-M version. All patients were systematically assigned to either a nurse (nurse 1) or a healthcare assistant (HCA 1) for their first PFFS-M assessment and a second assessment was done by a second staff member from the same professional category (nurse 2 and HCA 2) on the same day. All patients also had the PFFS-M completed by the clinic doctor. The research assistant completed the Adelaide Frailty Index. All patients returned after one week for a reassessment by the same health care professionals who had assessed them at recruitment stage and they were also required to complete the PFFS-M for a second time. The test-retest reliability was strong for patients (r=0.81), caregivers (r=0.90), HCA 1 and 2 (r=0.91 and 0.92), nurses’ 1 and 2 (r=0.91 and 0.92) and doctors (r=0.87). Inter-rater reliability assessments calculated for total PFFS-M scores by various combinations of participant type, and across all participants were good (ICC=0.81-0.95). The association between PFFS-M total score and the AFI was statistically significant (P value<0.0001). The PFFS-Malay version was found to have good reliability and validity within the Malaysian context.

S6- TRYPTOPHAN METABOLISM LINKS CHRONIC INFLAMMATION TO FUNCTIONAL DECLINE & PHYSICAL FRAILTY. Jeremy Walston (Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, USA)

Communication 1:Altered Tryptophan Metabolism Links Chronic Inflammation to Functional Decline & Physical Frailty in Mice and Humans, Reyhan Westbrook (Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, USA)

Chronic inflammation is associated with frailty and functional decline in older adults but the molecular mechanisms of this linkage are not well understood. The interleukin 10tm1Cgn (IL10tm) mouse develops chronic inflammation, a frailty-like phenotype with age, and has increased mortality making it an ideal model to study the biological mechanisms of frailty and functional decline. In order to pinpoint specific biological pathways that change with age as well as connect chronic inflammation to functional decline and physical frailty, we utilized a targeted metabolomic platform to agnostically identify differences inmetabolite levels in chronically inflamed IL10tm mice. Our initial profiling identified several metabolite alterations in the plasma of the IL10tm mouse compared to controls, with the most prominent and consistent alterations being in metabolites of the tryptophan degradation pathway (TDP), including decreased tryptophan and concomitantly increased kynurenine in middle-agedIL-10tm mice, and an intensification of these changes in old aged IL-10tm mice relative to controls. To translate these findings into human subjects, we then analyzed the composition of metabolites in the blood of a population of young, non-frail and frail older adults (n=166). Analysis of metabolites revealed significant alterations in the TDP with aging and frailty. Among the top metabolites to correlate with age and frailty status were kynurenine and the kynurenine/tryptophan ratio. The kynurenine/tryptophan ratio also tightly correlated with serum inflammatory cytokines TNFaR1 and IL-6. Higherkynurenine/ tryptophan levels were associated with weaker grip strength and slower walking speed, even after adjusting for age, gender, BMI and blood pressure. Profiling of downstream metabolites of the TDP revealed the accumulation of 3-hydroxykynurenine, a cytotoxic and neurotoxic intermediate metabolite, with frailty. The increased levels of cytotoxic and neurotoxic molecules in the TDP may in part explain the link between inflammation and cognitive and physical decline in frailty.

Communication 2:Neurotoxic Kynurenines are Linked to Reduced Neuromuscular Connectivity in a Mouse Model of Chronic Inflammation and Frailty, Tae Chung (Department of Physical Medicine and Rehabilitation, Johns Hopkins University School of Medicine, Baltimore, USA)

Chronic inflammation is known to be associated with frailty and sarcopenia, but the underlying mechanisms are not well understood. In order to pinpoint specific biological pathways that connect chronic inflammation to functional decline and physical frailty, we recently utilized a targeted metabolomic platform to identify categories or signatures of differences in metabolite levels and saw increased tryptophan degradation and production of kynurenines in the IL-10tm mouse model of chronic inflammation. Interestingly, some of kynurenine metabolites are neurotoxic and known to play a role in the pathogenesis of various neurodegenerative diseases, such as Alzheimer and Parkinson diseases. Therefore, we hypothesized that chronic inflammationis related to age-associated muscle weakness via neurotoxic kynurenines. We compared force vs frequency relationship between IL-10tm (n=8) and control (n=7) mice, and found that total isometric force is reduced in IL-10tm mice. The kinetics of contraction were also measured at 80Hz tetanic stimulation, and we saw that the maximal rate of contraction (+dF/dt) was significantly lower in IL-10tm mice. We then harvested EDL muscles and performed immunofluorescent staining of neuromuscular junction (NMJ) for morphological study. Using laser confocal microscope, we compared presynaptic to postsynaptic areas in a semi-quantitative way, and found that reduced presynaptic to postsynaptic coverage is significantly reduced in IL-10tm mice, suggesting increased partial denervation in their muscles. Finally, we tested the neurotoxicity of 3-hydroxykynurenine (3-HK) or quinolinic acid (QA) on a model of peripheral spinal motor neuron, MN1 cells. Both 3-HK and QA showed neurotoxicity at a higher concentration in a dose-dependent manner. However, these concentrations are much higher than physiological concentrations found in human. Interestingly, when MN1 cells are incubated with both 3-HK and QA, neurotoxicity is potentiated, and occurred at a concentration that can be found during inflammation and other conditions. In conclusion, our findings suggest that neurotoxic kynurenines may explain reduced neuromuscular connectivity and frailty phenotype in the IL-10tm mouse model of chronic inflammation.

Communication 3:Effects of tryptophan degradation pathway blockade on age-related decline in physical performance and life span of Drosophila melanogaster, Mariann M. Gabrawy (Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, USA)

The tryptophan degradation pathway (TDP) has been implicated as a contributor to frailty and life span. In humans, the TDP is activated by inflammation and produces kynurenines, some of which are neurotoxic or cytotoxic and, in frail older adults, are at elevated levels. Various components of the pathway are well-characterized and serve as therapeutic targets. However, the etiological role of altered kynurenine levels in reduced physical performance is not known. As the TDP is conserved across species and has homologues in Drosophila melanogaster, we used a previously characterized DGRP_229 line from the Drosophila Genetic Reference Panel and an established physical performance battery to elucidate the role of altered levels of kynurenines in age-related decline in climbing speed and endurance. To test whether increased levels of cytotoxic kynurenines will accelerate age-related decline in physical performance, flies were chronically fed 3-hydroxyanthranilic acid (3-HAA) and assayed at young, middle, and old age. We also tested whether blocking the production of kynurenines, via chronic treatment with alpha-methyl-tryptophan (alpha-MT) supplemented with nicotinamide (NAM), will improve physical performance. Further, we measured the effects of the aforementioned metabolites on survivorship. Our results show that flies treated with 3-HAA have accelerated age-related decline in climbing speed and endurance. Flies treated with a combination of alpha-MT and NAM have significantly improved speed and endurance than those treated with each metabolite alone. Treatment with 3-HAA significantly decreased life span while treatment with a combination of alpha-MT and NAM significantly increased life span. We conclude that treatment with alpha-MT and NAM attenuated the effects of age on the decline of physical performance in an age-specific manner while increasing survivorship.

S7- PROTEIN + EXERCISE INTERVENTIONS IN DIFFERENT POPULATIONS OF OLDER ADULTS. Lisette de Groot (Nutrition and Ageing, Wageningen University, Wageningen, The Netherlands)

Communication 1:Effectiveness of a combined diet and resistance exercise intervention on muscle health for community-dwelling older adults: ProMuscle in Practice study, Berber Dorhout (Wageningen University, Wageningen, The Netherlands)

The combination of resistance exercise (RE) and a protein-rich diet is effective in improving muscle mass and physical performance of older adults in a clinical setting. However, not much is known about the effectiveness of this strategy inpractice. We aimed to evaluate effectiveness of a RE and dietary protein intervention for older adults implemented in practice. This multicentre RCT included 168 Dutch community-dwelling older adults (75±6 years). The intervention group received a 12-week intensive support intervention, consisting of supervised RE and a protein-rich diet. After that, they received a 12-week moderate support intervention, to continue the adapted lifestyle pattern. The control group received no intervention. Physical functioning (Short Physical Performance Battery; SPPB), leg strength (MicroFET), lean body mass (DXA), and quality of life (EQ-5D-5L) were measured at baseline, after 12 and 24 weeks. After 12 and 24 weeks, the intervention group significantly increased their protein intake compared to control group (P<0.001). Also SPPB score increased in intervention participants (from 10.1±0.2 to 10.4±0.2 at week 12 and 10.6±0.2 at week24), whereas control participants decreased (time*treatment interactions P<.05). Additionally, leg strength and lean body mass improved in the intervention group compared to control group (P<.05), whereas no difference between groups was found for quality of life. This study shows that ProMuscle in Practice leads to improvements on muscle health-related outcomes incommunity-dwelling older adults. Further research should focus on feasibility of implementation in a real-life setting and improving long-term behaviour maintenance.

Communication 2:A combined nutrition and exercise intervention improves nutritional status and bone health of healthy Chinese middle-aged and older adults, Inge Groenendijk (Wageningen University, Wageningen, The Netherlands)

Hong Kong faces several public health problems including malnutrition, osteoporosis and its consequences. Considering the typical Chinese diet and the overall low physical activity levels of Chinese adults, there is a need for timely interventions to improve nutritional status and bone health. This study investigated the effects of a combined nutrition and exercise intervention on serum vitamin B-12 and 25(OH)D levels, bone turnover markers, and parathyroid hormone (PTH) levels in apparently healthy community-dwelling Chinese middle-aged and older adults. In this 24-week randomized controlled trial, 180 Chinese adults (85 women, mean age 61 y) were randomly assigned to receive two glasses of a fortified milk supplement and an exercise program or no intervention. Blood samples were collected at baseline, 12 and 24 weeks to assess vitamin B-12 and 25(OH)D levels, bone turnover markers, and PTH levels. A significant time x group interaction (p<0.001) was found for serum vitamin B-12 and 25(OH)D levels and the bone turnover markers, but not for PTH levels (p=0.09). The intervention increased vitamin B-12 levels from baseline (345±119 pmol/L) to 24 weeks (484±136 pmol/L), while levels remained stable within the control group. For 25(OH)D levels, the intervention group had a greater increase from baseline (54.7±14.2 nmol/L) to 24 weeks (80.1±19.2 nmol/L) compared to the control group (60.6±15.2 vs 65.6±14.6 nmol/L). The ratio of the net effect of bone formation and resorption was greater for the intervention group (median=0.70) than the control group (median=-0.11, p<0.001), suggesting less bone loss in the intervention group, irrespective of gender. This study showed that nutritional supplementation combined with exercise is effective in improving vitamin B-12 and 25(OH)D levels as well as the balance of bone turnover markers of apparently healthy community-dwelling Chinese middle-aged and older adults.

Communication 3:A 4-week exercise and protein prehabilitation program improves muscle mass and physical functioning in Dutch older adults, Pol Grootswagers (Wageningen University, Wageningen, The Netherlands)

Prehabilitation might attenuate common hospitalization-related losses in muscle mass and physical performance. Beneficial effects of physical exercise with protein supplementation have been reported in older adults multiple times before, but typically after an intervention of at least 12 weeks. The time-window for pre-surgery training is often limited, and it is not known if it is possible to achieve comparable results in such a short time window. The aim of this study was to pilot-test the effectiveness of a 4-week combined exercise and protein supplementation program on skeletal muscle related outcomes in a Dutch older adult population. Seventeen older sedentary men and women, aged 55–75y, were included in this one-armed pilot study. Participants followed a 4-week intervention program consisting of a twice-weekly supervised resistance and high-intensity aerobic exercise training of 75 min, combined with daily protein supplementation (30g). After two and four weeks, quadriceps cross-sectional area (CSA) was assessed via magnetic resonance imaging and isometric quadriceps maximal voluntary contraction (MVC) via Biodex. Other outcome measures were handgrip strength, chair rise time and maximal aerobic capacity (VO2-max). The 4-week exercise and protein program improved quadriceps CSA with 5% (Δ3.2±3.2 cm2, P=0.001), quadriceps MVC with 12% (Δ 17.1±24.1 Nm, P=0.004), VO2-max with 8% (Δ 2.4±5.5 ml/min/kg, P=0.016) and chair rise test with 19% (Δ-2.7(IQR −5.5,−2.3) sec, P<0.001). We observed no changes in body weight and handgrip strength. A 4-week exercise and protein intervention led to clinically relevant improvements in muscle-related outcomes in healthy older adults.

S9- COMMUNITY-BASED PRIMARY FRAILTY PREVENTION AND ITS IMPLEMENTATION AND DISSEMINATION. Hidenori Arai (National Center for Geriatrics and Gerontology, Minoru Yamada, Tsukuba University, Japan)

Communication 1:Community-based Prevention of Frailty: Japanese experience, Hidenori Arai (National Center for Geriatrics and Gerontology, Minoru Yamada, Tsukuba University, Japan)

Japan has a stunning percentage of older people in the population and preventing frailty and its adverse health outcomes is crucial for the healthy life expectancy. Since the long-term care insurance (LTCI) system was launched, the number of certified older adults with LTCI service requirement has continued to increase. This is a serious problem, because the LTCI service requirement certification is equivalent to disability and leads to long-term care cost. Therefore, the Japanese government has been focusing on the population approach to mitigate the increase of disabled older adults. The aim of this study was to evaluate the effect of a self-management group intervention on new LTCI service requirement certifications in community-dwelling older adults in Japan. In this prospective cohort study, we recruited community-dwelling adults aged 65 years and older who were independent in a city in Kyoto prefecture in 2012. The subjects in the participation group (n = 1620) attended 60-min group training sessions once or twice every two weeks from December 2012 to December 2016. The exercise sessions consisted of mild-intensity aerobic exercise, mild strength training, flexibility and balance exercises, and cool-downactivities. These exercise classes were facilitated by well-trained volunteer staff. The outcome measure was the number of new LTCI requirement certifications during a four-year follow-up period. During the four-year follow-up period, 247 subjects (15.2%) in the participation group and 334 (20.6%) in the control group were newly certified for LTCI service requirements. The hazard ratio for new LTCI service requirements in the participation group compared with the control group was 0.73 (95% CI =0.62-0.86) in the four-year follow-up period. These results indicate the usefulness of self-management group exercise to reduce the incidence of disability in older adults. We will show other interventions to prevent frailty and disability which can be applied to other communities.

Communication 2:SAYGo: Community-based Peer-led Classes to Improve Falls Risk, Frailty, and Social Connection, Debra L Waters (Director of Gerontology Research, University of Otago, New Zealand)

New Zealand has a long history of developing and delivering innovative programmes for older adults. These include the Otago Exercise Programme (OEP), Steady as You Go (SYGo), Senior Chef, and an adaptation of Australia’s Men’s Sheds. These interventions improve physical function and social connection through group settings and a peer-led class model. New Zealand has been successful in achieving long-term and scalability with the Steady as You Go (SAYGo) programme which has been running since 2003 and has more than 1500 participants and > 150 peer leaders in the Otago and Southland region alone. This programme was adapted from the OEP exercises to a group setting and has been shown to significantly improve strength and balance, to reduced falls by ~27%. Long-term participation (>3 years) has demonstrated significantly lower falls incidence (IRR0.90, 95%CI: 0.84 to 0.98, p=0.02) and also fewer injurious falls (p=0.03, β −.155, 95%CI −.115–0.005). More recently, there has been coordinated effort between Age Concern (charitable organizes across NZ), ACC- the New Zealand Crown entity responsible for administering the country’s universal no-fault accidental injury scheme, Health Quality Safety Commission, regional Public Health Organizations and Falls and Fracture Liaison Services in coordinating primary care falls screening, population-based falls incidence tracking and enrollment in regional strength and balance classes across New Zealand. It has resulted in a significant increase in older people attending strength and balance classes across the county. This model has worked well, but it has not been without its’ challenges. Developing and sustaining peer-led strength and balance classes requires specific features and support. This talk will present the development and evolution of SAYGo over the past 17 years inNew Zealand.

Communication 3:A Peer-Led Multi-Domain Community Program to Reverse Frailty and Improve Cognition: HAPPY Outcomes, Reshma A Merchant (National University Health System, Singapore)

With rapid increase in ageing population, especially in Asian countries, the prevalence of frailty, dementia and associated consequence including falls and disability will increase putting a strain on finite healthcare resources and shrinking workforce. Multidomain interventions including physical exercise and cognitive training, conducted in group settings have shown to postpone and / or reverse cognitive impairment and frailty. Many countries have tried different approaches to sustain and scale up community interventions to prevent frailty and dementia, and to improve overall population health and psychosocial wellbeing. Healthy Ageing Promotion Program For You (HAPPY) is an all in one successful community based peer-led multidomain intervention conducted island wide in Singapore in more than 70 different locations in partnership with Agency of Integrated Care. HAPPY is adapted from cognicise in Nagoya Japan, and comprises of more than 200 dual task exercises and self empowerment. The program is led by trained peer-leaders which makes it sustainable and easily scalable. More than 50% improved in frailty scores, and almost half of those initially classified as pre-frail became robust at the end of 6 months. More than 2/3 improved in cognitive scores with 1/3 self-reported improvement in memory. Almost half had improvement in depression scores. A peer-led group intervention program with incorporates physical activity, cognition training and at the same time empowering the seniors is effective in reversing frailty and improving cognition. This talk will share the implementation tips and challenges.

S10- “WHY” RATHER THAN “HOW”: A TRANS-PARADIGMATIC DISCUSSION ON THE URGENCY OF THE FRAILTY CONCEPT FOR OPTIMIZING OUTCOMES FOR OLDER ADULTS. Susan E Howlett1,2, Karen Bandeen-Roche3, Brian Buta4, Ravi Varadhan5, Qian-Li Xue2, Matteo Cesari6,7, Emanuele Marzetti8((1) Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada; (2) Department of Medicine / Geriatrics, Dalhousie University, Halifax, Nova Scotia, Canada; (3) Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; (4) Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA; (5) Department of Oncology, Johns Hopkins School of Medicine,Baltimore, MD, USA; (6) Department of Clinical Science and Community Health, University of Milan, Milan, Italy; (7) Geriatric Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; (8) IRCCS Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy)

As the world’s population ages, there is urgent need for strategies by which to extend health, function and independence for older adults. Frailty holds high promise as a focus by which to advance this goal, because this concept characterizes individuals who become vulnerable to stressors and so are at risk for adverse health and functioning outcomes. Frailty assessment therefore stands to accelerate efforts to extend healthy aging in older populations and to optimally manage older adults’ care in clinical settings. Yet, theories as to the nature of frailty, as well as methods for its measurement, are highly diverse. This sometimes confuses practitioners seeking to implement frailty in health care settings and hampers development and dissemination of best practices into public health and clinical domains. This symposium features speakers representing three of the leading paradigms framing frailty research, practice and implementation efforts: Deficit Accumulation, the Physical Frailty Phenotype, and the Physical Frailty & Sarcopenia (PF&S). It aims to communicate their paradigms’ goals in frailty assessment, rather than to debate methodology. Speakers specifically are charged with addressing, for each paradigm: 1) How is frailty conceptualized? 2) What is the importance of frailty for older individuals, for public health policy and practice aimed at older adults, and for clinical care of older adults? How can frailty assessment and/or management be of benefit in these areas? 3) What are the highest research imperatives / gaps to address in order for the envisioned benefits to be realized?

S11- MUSCLE MASS WITH THE D3-CREATINE DILUTION METHOD: PRACTICAL ASPECTS OF IMPLEMENTATION AND DATA ON THE RELATIONSHIP OF MUSCLEMASS WITH HEALTH-RELATED OUTCOMES IN OLD MEN. Luigi Ferrucci (National Institute on Aging, National Institutes of Health, Baltimore, MD, USA)

Communication 1:Methodology — Description of preclinical and clinical validation studies. How to employ the method into clinical trials including large cohort studies and randomized, controlled trials, William J. Evans (University of California, Berkeley, USA)

The assessment of total body skeletal muscle mass has, until recently, been problematic. Skeletal muscle is a significant but not the only component of lean body mass (LBM). In a large number of clinical trials LBM is incorrectly referred to as muscle massand, as a result use of LBM as a surrogate for muscle mass has resulted in erroneous conclusions on the importance of skeletal muscle in development of late-life dysfunction and risk of chronic disease. The D3-Creatine (D3Cr) dilution method allows adirect and accurate measurement of skeletal muscle mass that is undiluted by hydration status or accumulation of intramyocellular fibrosis or lipid. The method provides a measurement of creatine pool size and, because ~98% of the body creatine pool is located in the sarcomere, muscle mass. Because the method is non-invasive and only requires a single fast ingurine sample, the method is ideal to measure muscle mass in large cohort studies. The method has been incorporated into a large prospective longitudinal trial in more than 1,300 older men (MrOS corhort, > 80 yr). This method employs an enteral doseof a specific amount of deuterated creatine (D3Cr). The tracer is absorbed and transported into the sarcomere. The D3Cr is irreversibly converted to D3-creatinine (D3Crn) and excreted, thus allowing the measurement of D3Crn enrichment from asingle, fasting urine sample. Details of dosing, sampling, and measuring muscle mass in longitudinal studies will be discussed.

Communication 2:D3Cr muscle mass and assessment skeletal muscle quality. Is Sarcopenic Obesity an anachronistic term? Eric Orwoll (Oregon Health Science University, USA)

The combination of sarcopenia and obesity has been associated with physical dysfunction in older people. However, because accurate assessments of muscle are challenging, previous research has relied on assessments of lean mass as a surrogate for muscle mass. We postulate that inaccurate measures of muscle mass may have led to a misunderstanding of the role of obesity in sarcopenia and related outcomes. We compared a direct measurement of muscle mass (D3 creatine dilution; D3Cr) with acommonly-used approximation of muscle mass (appendicular lean mass (ALM) by dual energy x-ray absorptiometry (DXA)) and their associations with measures of physical performance (gait speed, chair stand time) and adverse outcomes (incident injurious falls and mobility problems). Data on the relationship of body fatness and muscle mass on walking speed suggests that sarcopenic obesity and risk of disability may not be a risk factor when muscle mass is accurately measured.

Communication 3:Muscle mass as a powerful risk factor for health-related outcomes in older people, Peggy Cawthon (California Pacific Medical Center, USA)

The use of inaccurate measurements of muscle has resulted in an assumption that muscle mass is not associated with late-life disability and health related outcomes. Sarcopenia definitions are controversial and none, so far, have used muscle mass. We review the current evidence, and highlight what additional steps are needed to support the use of d3-creatine to define sarcopenia.

S12- ASSESSMENT OF QUALITY OF LIFE IN SARCOPENIA: FROM CLINICAL TRIALS TO DAILY PRACTICE. Charlotte Beaudart (WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Division of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium)

Communication 1:Importance of patients related outcomes measures (PROM) as primary endpoints for the development of medications aimed at the treatment of diseases related to musculoskeletal outcomes, Francesca Cerreta (Human Medicines Research and Development Support Division, Scientific Advice, London, UK)

The association between sarcopenia and quality of life became a topic of high interest in the past 10 last years. The prospective and generalized loss of muscle mass, muscle strength, physical performance and muscle quality resulting from sarcopenia could contribute to a lower QoL in sarcopenia. HR-QoL assessments are important for healthcare providers and regulatory agencies to understand the needs and preoccupation of important segments of the population, such as elderly subjects suffering from sarcopenia. Moreover, with the future expected development of interventions targeting sarcopenia, Patients Reported Outcomes (PROMs) such as quality of life questionnaires will also be useful to measure the effectiveness and relevance of these new therapeutic strategies. Indeed, complete assessment of the benefits of a therapeutic intervention should provide evidence of an impact on patients’ HR-QoL.

Communication 2:Assessment of quality of life in sarcopenia with the SarQoL questionnaire: where do we stand? Charlotte Beaudart (WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Division of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium)

For sarcopenic patients, literature and patient surveys indicates that the QoL impact is felt on physical and functional domains, and that the use of generic measures could lack the specificity and sensitivity needed to capture a detailed and accurate picture of the quality of life of these patients. The SarQoL questionnaire, a specific HR-QoL questionnaire for sarcopenia developed in 2015, has demonstrated in several studies that it is a valid and reliable instrument for measuring quality of life in sarcopenic older people. As it is relevant both in observational and interventional studies, the smallest detectable change of the SarQoL has also recently been measured. On individual subjects, a change in overall quality of life of at least 7.35 points (on a scale from 0 to 100) would have to be observed to confirm that a true change, beyond measurement error, has occurred. This questionnaire is recommended both in research and clinical practice but also in clinical trials, since its responsiveness has recently been demonstrated.

Communication 3:Discussion — conclusion, Olivier Bruyère (Belgium)

S13- EVIDENCE AND POSITION STATEMENTS FROM THE SARCOPENIA DEFINITIONS AND OUTCOME CONSORTIUM (SDOC). Roger Fielding (Tufts University, Boston, USA)

Communication 1:Evidence for deriving cutpoints for defining sarcopenia, Todd Manini (USA)

Communication 2:Evidence for performance of potential sarcopenia variables predicting outcomes, Peggy Cawthon (USA)

Communication 3:SDOC Position Statements: process and conclusions, Shalender Bhasin (USA)

S14- INNOVATIONS IN NON-PHARMACOLOGICAL INTERVENTIONS TO KEEP AGEING MUSCLES STRONG AND AGILE AND THE MIND SHARP. Robin M. Daly (Institute for Physical Activity and Nutrition, Deakin University, Melbourne, Victoria, Australia)

Communication 1:Novel nutritional approaches to enhance the effects of exercise on muscle, mobility and the mind in older people, Robin M. Daly (Institute for Physical Activity and Nutrition, Deakin University, Melbourne, Victoria, Australia)

Sarcopenia and cognitive impairment can occur simultaneously in older adults, and collectively have been linked to an increased risk for frailty, falls, disability and dementia. While it has been suggested that this association is bidirectional (eg. factors causing sarcopenia can contribute to cognitive impairment or vice versa), there are many similarities in the pathophysiological pathways to both these conditions. Both are multifactorial in origin, and their onset and progression share many of the same risk factors, including inadequate nutrition and physical inactivity. It is likely that the multi-faceted nature of both these conditions has contributed to the mixed findings reported from various trials with regard to the efficacy of single-domain interventions (eg. exercise, nutrition, cognitive training) on both cognitive function and muscle loss. As a result, it has been suggested that an integrated approach incorporating multi-factorial interventions that simultaneously target muscle and cognitive function and their underlying risk factors may provide the greatest benefits. This presentation will provide an update of the evidence from recent large-scale intervention trials which have evaluated the efficacy and effectiveness of multi-factorial approaches incorporating both exercise and various nutritional factors (beyond dietary protein alone), including vitamin D, omega-3 fatty acids, creatine, phospholipids, multi-nutrient supplements and various diets (Mediterranean diet) or foods (dairy products), on cognition, dementia risk, muscle health and functional performance in older people. This will include several of our recent trials in which we evaluated whether multi-modal resistance-based exercise programs combined with either a protein enriched diet achieved through lean red meat or multi-nutrient supplemental drinks enriched with vitamin D, whey protein, omega-3 fatty acids and/or phospholipids, can improve cognitive function as well as muscle mass, strength and function in older adults, those with memory complaints and type 2 diabetes.

Communication 2:Importance of initial protein intake on muscle function during aging and following an exercise intervention, Mylene Aubertin-Leheudre1,2 ((1) Department of Exercise Sciences, Groupe de recherche en activité physique adapté (GRAPA), Université du Québec à Montréal, Montreal (Qc), Canada; (2) Centre de Recherche de l’Institut Universitaire de Gériatrie de Montréal, Montreal (Qc), Canada)

Aging is associated with losses of muscle mass, strength and quality which are strong risk factors of functional impairment. One potential mechanism that could explain this age-related muscle loss, in addition to age or physical inactivity, is protein intake. It has been shown that the amount and the distribution of protein intake could influence physical performance changes occurring during the aging process, even in community living older adults. In addition, it seems that loss of muscle strength (dynapenia) is a better predictor of physical limitations than loss of muscle mass (sarcopenia) or gain of fat-mass (obesity). Nevertheless, these body composition modifications can be combined and lead to worsening health effects in older adults. Thus, determining their specific impact, and if it is dependent of body composition profiles, is important. The first part of this presentation will address these questions. In addition, physical activity is one of the most promising non-pharmacological avenues to counteract functional incapacities. More precisely, it has been proposed than aerobic training (such as High Intensity Interval Training (HIIT)) or resistance (power) training are both efficient to maintain muscle quality in older adults aged over 65 years. Nevertheless, lifestyle habits (such as protein intake) seem able to influence muscle adaptations following exercise intervention to improve body composition and functional capacities in older people. Thus, the second aim of this presentation will be to evaluate if the initial amount of protein intake could influence body composition, muscle strength and functional capacity improvements following an exercise training (power or interval training) intervention combined or not with nutritional supplementation (citrulline) in older adults.

Communication 3:Assistive technologies for supporting healthy nutrition behaviours in community-dwelling older adults now and in the (not too distant) future, Dr David Scott1,2 ((1) School of Clinical Sciences at Monash Health, Monash University, Australia; (2) Australian Institute for Musculoskeletal Science, Department of Medicine — Western Health, The University of Melbourne, Australia)

Assistive technologies are devices or systems used to maintain or improve physical functioning in populations with disability. Community-dwelling older adults represent an important population who commonly experience limitations in activities of daily living, and these disabilities can potentially contribute to unhealthy nutrition behaviours which may exacerbate functional declines. Thus, poor nutrition is likely to be an important contributor to the anticipated unsustainable demand for aged care services in the coming decades. Commonly used assistive technologies to support nutrition behaviours in older adults with functional limitations currently include simple devices which aid in preparation and consumption of food. Emerging assistive technologies may in future support older adults with disability to better maintain their independence and age in place. Smart homes of the future will include numerous connected appliances and sensors that can assist older adults to maintain adequate nutrition through monitoring dietary intake, providing meal reminders and individualised eating plans, and ordering food through online delivery services. Robotics and exoskeleton devices may also play a role in supporting food preparation. Furthermore, three-dimensional food printers may in coming years allow meals to be printed in the home. These customisable meals can provide specific nutrient contents which support individuals in meeting recommended dietary intakes, and also ensure safe consumption for those with age-related oral health issues. Nonetheless, emerging assistive technologies need to be developed while taking into consideration individual privacy concerns, common issues of patient abandonment of devices, and in particular, the need to prioritise movement over sedentary behaviour in older individuals. This presentation will summarise strategies by which emerging assistive technologies may support nutrition behaviours in the home for older adults, thereby reducing demand on aged care. It will also propose several research questions which need to be addressed in order to confirm feasibility, safety and effectiveness of these technologies.

Conference

C1- THE SENESCENCE-ASSOCIATED SECRETOME AS A BIOMARKER OF AGE AND MEDICAL RISK. Marissa J. Schafer, Xu Zhang, Amanika Kumar, Thomas A. White, Sarah K. Jachim, Elizabeth J. Atkinson, Nathan K. LeBrasseur (Mayo Clinic, Rochester, MN, USA)

Backgrounds: Senescent cells accumulate with advancing age and, in part, drive tissue degeneration and compromise tissue rejuvenation through their robust secretome, the senescence-associated secretory phenotype (SASP). Objectives: The objectives of this study were to develop a candidate panel of senescence biomarkers, determine the extent to which components of the SASP can be reliably detected in human blood, and examine whether circulating concentrations associate with parameters of biological age in humans. Methods: We first assessed whether predefined SASP proteins were abundantly secreted by senescent compared to non-senescent human cells of the same origin. Next, we determined whether candidate SASP factors could be reliably measured in human plasma and tested their associations with chronological age (280 men and women 20 to 90 years of age). We then assessed the associations between plasma biomarkers and biological age, as quantified by the frailty index, in relatively healthy older adults, and older adults undergoing surgery for either aortic stenosis or ovarian cancer. In the surgical groups, we also tested associations of plasma biomarkers with adverse outcomes, including complications (e.g., pneumonia, stroke, infection), ICU admission, and/or hospital readmission. Results: High levels of both distinct and overlapping SASP factors were identified in all senescent cells assayed, relative to non-senescent cells, with the largest increase in SASP produced by senescent endothelial cells and preadipocytes. Circulating concentrations of 19 out of 24 SASP proteins were associated with chronological age. GDF15 and activin A were the strongest biomarkers of chronological age. Eleven SASP factors were associated with the frailty index in any one of the three participant groups, with CCL4, GDF15, OPN, and TNFR1 significantly associated in all three, even after adjustment for effect modifiers. Gradient boosting machine modeling identified a single panel of seven biomarkers that was consistently able to predict adverse events in both surgical populations better than chronological age + sex, a single biomarker, or frailty index. Conclusion: These results support the hypothesis that circulating SASP factors are informative biomarkers of biological age that may be leveraged to predict risk for adverse health outcomes in a disease-agnostic manner. The biomarkers may have considerable relevance for clinical practice and clinical research

C2- FRAILTY AND CARDIOVASCULAR DISEASE (CVD): A COMPLEX RELATIONSHIP. Nicola Veronese, (Consiglio Nazionale delle Ricerche, Padova, Italy)

Dr Veronese will talk about the association between frailty and CVD in terms of epidemiological evidence. This association is relatively new in geriatric medicine particularly for the studies assessing the impact of frailty in predicting the onset of CVD. Some parts will be spent for explaining the newer studies reporting data on this important issue that probably suggests a bi-univocal relationship between frailty and CVD.

C3- FRAILTY AND ITS ASSOCIATION WITH POTENTIAL BIOMARKERS AT BASELINE — FIRST RESULTS FROM DO-HEALTH. Michael Gagesch1,2, Patricia Chocano-Bedoya1,2, Reto W. Kressig3, Bruno Vellas4, René Rizzoli5, Heike A. Bischoff-Ferrari1,2 for the DO-HEALTH investigators ((1) Department of Geriatrics and Aging Research, University Hospital Zurich and University of Zurich, Zurich, Switzerland; (2) Centre on Aging and Mobility, University of Zurich, Zurich, Switzerland; (3) University of Basel, Switzerland; (4) Felix Platter Hospital, Basel, Switzerland; (5) Gerontopôle, University of Toulouse, France; (6) University of Geneva, Switzerland)

Backgrounds: Chronic low-grade inflammation (CI) is a risk factor for adverse outcomes in older adults and has been linked to frailty. Further, CI and frailty are associated with cardiovascular disease (CVD). Finally, insulin resistance (IR) is a pathophysiologic state connected to CI, CVD and frailty. Objectives: To investigate the association between two inflammatory biomarkers (CRP, IL-6) and two heart health biomarkers (NT-pro BNP and HOMA-IR) with frailty among DO-HEALTH participants at baseline. Methods: Cross-sectional analysis of baseline findings in the DO-HEALTH trial including all 2157 community-dwelling participants age 70+from five European countries. We used the Fried phenotype to identify frail, pre-frail and robust adults. Because of the skewed distributions of all biomarkers, we used logarithmic transformations and report geometric means. Mean biomarker levels by frailty status were compared with ANOVA. We investigated the association between CRP, IL-6, NT-pro BNP and HOMA-IR and frailty using multinomial regression with the ‘robust’ group as the reference, adjusting for age, gender, BMI, center, and priorfalls. For NT-proBNP we additionally adjusted for reported cardiovascular disease and tropon in levels for NT-proBNP and reported diabetes for HOMA-IR levels. Results: 3.1% of participants were frail and 44% were pre-frail. Mean IL-6 level (pg/L) was 2.54 in robust, 2.84 in pre-frail and 3.89 in frail participants (P Value <0.0001). Mean NT-pro BNP level (ng/L) was 108.7 in robust, 126.9 in pre-frail and 155.1 in frail participants (P Value <0.0001). There were no significant differences in the mean CRP and mean HOMA-IR levels by frailty status. Cross-sectionally, participants with IL-6 levels in the highest tertile (median 4.6 pg/L, range 3.3-188.8) were 1.3-fold more likely pre-frail (OR=1.34, 95% CI=1.06–1.67) and more than 2-fold more likely frail (OR=2.18, 95% CI=1.03–4.59) after adjustment for age, gender, center, BMI and prior falls. There were no significant differences for CRP, HOMA-IR and NT-proBNP regarding frailty status. Conclusion: In this cross-sectional analysis, higher levels of IL-6 and higher levels of NT-proBNP were found in frail participants in DO-HEALTH at baseline. No significant associations were found between CRP or HOMA-IR and frailty status

C4- EFFECTS OF FORTETROPIN® ON THE RATE

OF MUSCLE PROTEIN SYNTHESIS IN OLDER MEN AND WOMEN: A RANDOMIZED, DOUBLE-BLINDED CONTROLSTUDY. William Evans1, Mahalakshmi Shankaran1, Edna Nyangau1, Tyler Field1, Hussein Mohammed1, Robert Wolfe2, Scott Schutzler2, Marc Hellerstein ((1) University of California Berkeley, USA; (2) University of Arkansas for Medical Sciences, USA)

Backgrounds: Fortetropin is an all-natural proteo-lipid complex made from fertilized egg yolk and has been demonstrated to lower circulating myostatin levels. In young men, Fortetropin supplementation has been shown to increase lean body mass compared to placebo. Objectives: The purpose of this study was to examine the effects of Fortetropin supplementation on the fractional rate of muscle protein synthesis (FSR) in healthy, older men and women. Methods: We used 2H2O labeling to measure the rate of synthesis of multiple muscle protein ontologies in 10 men and 10 women (66.4 ±4.5 yr). All subjects received 30 mg of D3-creatine prior to submitting a fasting urine sample to determine muscle mass at baseline. On days 1, 2, 3, and 4, subjects ingested 50 ml of 70% 2H2O TID, and BID for 17 days. Saliva samples were collected to determine body 2H2O enrichment on study days 4, 7, 14, and 21. A muscle microbiopsy (~10 mg) was taken from the m.vastus lateralis on day 21. Subjects were randomly assigned to Fortetropin (19.8 g/d) or placebo (cheese powder 19.8 g/d). In-solution digestion with trypsin was performed on SDS-soluble proteins prior to LC/MS-MS analysis using 27-min gradientruns. FSR was calculated with average body water used as the precursor enrichment. Results: Body water enrichments reached an average plateau of ~1.5% during labeling period. MS/MS analysis identified 210 proteins with >= 2 peptides/protein. Kinetic data comprised 117 proteins meeting analytic criteria including >= 2 peptides measured in at least 4 subjects per group. The average FSR for a majority of proteins in several muscle gene ontologies was higher in the Fortetropin group compared to placebo (33/38 myofibril, 36/44 cytoplasmic and 15/19 mitochondrial proteins) and this proportion was significant using a Binomial Test. The effects of Fortetropin were independent of sex or baseline muscle mass. Conclusion: The overall magnitude of increase was 15%, demonstrating a stimulatory effect of Fortetropin on muscle protein FSR, with multiple gene ontologies affected. While these results should be confirmed in larger cohorts, they suggest that oral Fortetropin supplementation is safe and effective for promoting muscle growth in older men and women.

C5- NIH MOLECULAR TRANSDUCERS OF PHYSICAL ACTIVITY CONSORTIUM (MOTRPAC) PROGRESS. Lyndon Joseph (National Institute on Aging, Bethesda Maryland, USA)

Backgrounds: Physical activity is beneficial to human health and well being across the lifespan. The numerous benefits of regular physical activity have long been recognized. Despite this, most exercise studies are associational and the molecular mechanisms that are the bases for the beneficial effects remain obscure as are the mechanisms of multi-organ communications and benefits. Objectives: The NIH Common Fund initiated the Molecular Transducers of Physical Activity Consortium (MoTrPAC) in December 2016 by issuing 19 grants to 37 Principal Investigators from 23 institutions. Fundamentally, MoTrPAC is a large discovery project the goals of which are to: Aim 1: Assemble a comprehensive map of the molecular changes that occur in response to exercise and provide insights into how they are altered by age, sex, body composition and fitness level. Aim 2: Develop a user-friendly database to facilitate investigator-initiated studies and catalyze the field of physical activity research whereby researchers can develop hypotheses exploring novel mechanisms by which physical activity improves or preserves health. Methods: This project will explore and document changes in molecules mobilized in blood, muscle and fat in humans as well as 15 additional tissues for rats in response to different exercise regimes (Resistance and Aerobic exercise intervention). The human studies are a multi-center clinical trial cohort of people of both sexes from 10–80 years of age. Preclinical animal Studies (PASS) have been conducted in 6 and 18-month old F344 rats and tissues harvested from control inactive rats and rats at seven time-points following a single 30 minute acute bout of treadmill running. A separate group of rats were subjected to an intensive (70% VO2max) and progressive run training program of 5 day/week for 1,2, 4, or 8 weeks with 18 tissues collected per rat. Multiple state of art and omics platforms including genomic, transcriptomic, epigenomic, proteomic and metabolomics are being employed to define and discover the molecules mobilized in response to exercise that will serve as a valuable resource for the research community and support future investigator-initiated studies to understand the molecular mechanisms of exercises effects. Results: This presentation will highlight data from the initial public data release (November 15th, 2019). Data will be available to the extramural community to collaborate with the MoTrPAC investigators to explore innovative mechanisms to expand the impact of the initial studies. PASS tissues not analyzed are stored in the MoTrPAC BioRepository and will be available for ancillary studies. Conclusion: The product from this consortium will begin to characterize the molecular mechanisms of molecules identified in the ‘molecular map’ that underlie the beneficial effects of physical activity. In addition, the publicly available data resource will help to enhance and accelerate subsequent mechanistic research on overall physiology and diseases and/or conditions affected by physical activity.

C6- ADAPTATION AND VALIDATION OF A SCALE TO ASSESS INTRINSIC CAPACITY IN MEXICAN COMMUNITY-DWELLING ELDERLY ADULTS. Luis Miguel Gutiérrez-Robledo, Rosa Estela García-Chanes, Oscar Rosas-Carrasco (Instituto Nacional de Geriatría, México)

Backgrounds: Intrinsic capacity (IC) is a composite of all the physical and mental attributes on which an individual can draw, not only in older age, but across their lives. Following the construct proposed by the WHO clinical consortium, we have developed and validated an Intrinsic Capacity (IC) scale suitable for use in clinical practice, consisting of 5 domains: cognition, psychological, sensory, vitality and Iocomotion. Objectives: To develop and validate a clinically useful IC measurement scale in a sample of community-dwelling Mexican older adults. Methods: Data for this analysis come from Frailty Dynapenia and Sarcopenia in Mexican Adults, a cohort of community-dwelling adults, from 2 municipalities in Mexico City. Each domain is measured either with 0 1, 0r 2 points for a total score from 0–10 (0 low IC to10 Optimal IC). To evaluate cognition we used the MMSE. The 7-item CES-D to analysis the psychological domain. The Snellen Eye Test to measure visual acuity and the self-report of hearing to assess the sensory domain. For the evaluation of vitality, the phase angle derived from bioimpedance measurement was used. For locomotion, gait speed and grip strength were assessed. For validation we tested internal consistency, known-group validity based on age and validity by construct with factor analysis. Results: The IC score showed reliability (Cronbach alfa=0.49). All item in the scale correlated to the scale’s total scare, rho=.36 to .68). The IC score decreases with age (p<0.05). The scale was also positively correlated to other related measurements (Quality oflife), short physical performance (SPPB) and negatively correlated with SARC-F, Frailty phenotype and Gerontopôle Frailty scale. The factor analysis demonstrated substantial, clustering of each domain to a single factor. Conclusion: We propose a new, clinically useful intrinsic capacity scale awaiting prospective validatione.

C7- EFFECTS OF A BLENDED HOME-BASED EXERCISE PROGRAM AND DIETARY PROTEIN INTERVENTION ON PHYSICAL PERFORMANCE INCOMMUNITY-DWELLING OLDER ADULTS: RESULTS FROM THE VITAMIN CRCT. Jantine van den Helder1,2, Sumit Mehra3,4, Carliene van Dronkelaar1, Gerben ter Riet1, Michael Tieland1, Bart Visser1, Ben J.A. Kröse3,5, Raoul H.H. Engelbert1,6, Peter J.M. Weijs1,7,8((1) Center of Expertise Urban Vitality, Amsterdam University of Applied Sciences; (2) Amsterdam University Medical Centers, VU University, Amsterdam Movement Sciences; (3) CREATE-IT Applied Research, Amsterdam University of Applied Sciences; (4) Faculty of Applied Social Sciences and Law, Amsterdam University of Applied Sciences; (5) Informatics Institute, University of Amsterdam; (6) Department of Rehabilitation, Amsterdam University Medical Centers, University of Amsterdam; (7) Department of Nutrition and Dietetics, Amsterdam University Medical Centers, VU University; (8) Amsterdam Public Health research institute, Amsterdam University Medical Centers, VU University; Amsterdam, The Netherlands)

Backgrounds: With the aging population, there is an increasing demand for strategies to optimize muscle mass, strength and physical performance in community dwelling older adults. We designed a new innovative e-health intervention “VITAMIN”, including behavior change techniques in exercise and nutrition, and targeting on improvement of physical performance in older adults. The blended home-based exercise intervention contains an exercise application with personalized coaching. Additionally, a dietary protein counseling intervention was designed to complement the exercise intervention. Objectives: To determine the 6-months effectiveness and 12-months sustainability of blended home-based exercise and dietary protein counseling interventions on physical performance in community-dwelling older adults. Methods: This cluster randomized controlled trial randomized community-dwelling older adults with a regular weekly exercise program into three research groups; 1) no intervention (Control), 2) blended home-based exercise intervention (HBex) or 3) blended home-based exercise intervention with dietary protein counseling (HBex-Pro). The entire study included a 6-month intervention period and a 6-month follow-up. The primary outcome was physical performance assessed by the modified physical performance test (m-PPT). Secondary outcomes included the categories physical functioning, nutritional status, health status, executive functioning and adherence to interventions. An intent-to-treat analytic strategy with Linear Mixed Models of repeated measures was applied to analyze changes over time. Results: In total 245 older adults were randomized, mean[SD] age 72.0[6.5] years, 71% was female, 44% low education and 54% had comorbidities. For m-PPT no significant intervention effects (HBex,p=.933; HBex-Pro,p=.730) or follow-up effects (HBex,p=.396;HBex-Pro,p=.362) were found. Gait speed, physical activity level, protein intake, appendicular muscle mass, and muscle strength improved significantly in HBex-Pro compared to Control after 6-month intervention. The protein intake, as well as muscle mass and strength remained significantly improved after 12-months as compared to Control. Conclusion: Although the interventions showed no effect on physical performance, clinically relevant changes were observed in protein intake, muscle mass and physical functioning after 6-months and remained improved after 12-months. Blended home-based exercise training and dietary protein counseling are promising and sustainable strategies to counteract the decline in musclemass and physical functioning in an aging population. Key words: Aging, Behavioral interventions, E-health, Exercise, Sarcopenia.

C8- DEVELOPMENT OF A NEW DEVICE FOR ASSESSMENT OF WIDE CROSS-SECTIONAL AREAS OF THE THIGH MUSCLE. Yasumoto Matsui1, Yasuo Suzuki1,2, Tsuyoshi Watanabe1, Hiroki Iida1, Kazumasa Yamada1, Satoshi Nakamura3, Tatsuo Arai3, Hidenori Arai1((1) National Center for Geriatrics and Gerontology, Japan; (2) Nihon Fukushi University, Faculty of Health Sciences, Department of Human Care Engineering, Japan; (3) Furuno Electrics Co, Ltd, Japan)

Backgrounds: According to EWGSOP2, computed tomography (CT) can be used in addition to dual X-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA) for measuring muscle mass to diagnose sarcopenia. However, CT has some limitations in its clinical application. We developed a new diagnostic device that produces a wide cross-sectional area (CSA) of the muscle using ultrasonography (US). Objective: The aim of this presentation was to present the images, evaluation methods, and reliability of our newly developed device and to compare them with CT images taken at the same site. Methods: The reliability was assessed by three examiners by measuring the mid-thigh area of three volunteers, and the intra-rater and inter-rater reliability were calculated. In addition, the correlation between the CSA of the CT and US images, and between the CT value (CTV) and echo intensity were investigated using the Pearson correlation coefficient. The subjects were 58 participants (23 men and 35 women) whose mean age was 71.1 years and who visited the Integrated Healthy Aging Clinic of our hospital. CT images were analyzed using the Slice Omatic software. Results: It took approximately 15 seconds to obtain the whole image of the quadriceps, which displayed an image similar to that of CT. The reproducibility study demonstrated that both the intra-rater and inter-rater reliability were high, with ICC (1,1) of 0.968 and ICC (3,1) of 0.934, respectively. Furthermore, a correlation was found between the CSA on CT and that on US (Pearson correlation, 0.996; p < 0.000). and a correlation was found between CTV and echo intensity (Pearson correlation, 0.785; p < 0.000). Discussion and Conclusion: The new ultrasonography diagnostic device for muscle assessment can produce a wide range of images similar to CT. As the echo intensity of the muscle image is considered to represent the intra-muscle adipose tissue and our new device demonstrated high reproducibility and correlated with CT in terms of CSA and CTV, our new device is expected to be a novel and effective tool for the diagnosis of sarcopenia in the future.

C9- THE GERIATRIC FRAILTY CLINIC IN TOULOUSE: PRESENTATION AND DESCRIPTIVE ANALYSIS OF 5000 PATIENTS. Sandrine Sourdet, Zara Steinmeyer, Anne Ghisolfi, Thomas Gemar, Bruno Chicoulaa, Bruno Vellas (Gérontopôle, Department of Internal Medicine and Geriatrics, Toulouse University Hospital, France)

Background: Frailty is a geriatric syndrome, defined as a state of decline in physiological reserves and increased vulnerability to stressors, and that result in greater risk of falls, disability and death. It is a potentially reversible process that can regress to a non-frail condition, with appropriate and preventive management including physical and nutritional interventions, optimization of drug prescription and management of comorbidities. Therefore, identifying and managing frailty is an opportunity to prevent or delay negative health outcome. In 2011, the geriatric “Frailty clinic” was created in Toulouse, France. This unit aims to assess frail older adults identified mainly in primary care, to look after the causes of frailty and to propose personalized preventive interventions. Objectives: The objective is to describe the organization of the Frailty clinic, and the main characteristics of the first 5000 patients evaluated between 2011 and 2018. Methods: The geriatric frailty clinic (GFC) is a geriatric day hospital dedicated to the prevention of disability in frail older patients aged 65 years and older. Patients considered frail by their physician (general practitioner (GP), geriatrist or specialist) in the Toulouse area are referred to the GFC. Each patient benefits from a comprehensive geriatric assessment performed by a multidisciplinary geriatric team (including a geriatrist or a GP trained in geriatrics, a nurse, nurse-aid, orthoptist, a dietician, neuropsychologist, and a physical activity teacher). Results: A total of 5000 patients were admitted between october 2011 and octobre 2019. We will perform a descriptive analysis of our population: 1/ socio-demographic characteristics, 2/ the frailty status (using Fried criteria); 3/ the cognitive status (MMSE score), 3/ physical status (Short Physical Performance Battery, Katz’s Activities of Daily living, Lawton’s Instrumental Activities of Daily Living), 4/ the nutritional status (Mini Mental Assessment score), 5/ sensory assessment. We will also describe the type of preventive interventions proposed to the patients, and follow-up data. Conclusion: The frailty clinic is the first unit dedicated to frailty management in France. Our experience demonstrates that frailty identification and management is feasible in clinical routine, with the implication of primary care professionals and the support of a multidisciplinary team.

C10- IMPLEMENTING EXERCICE THROUGHOUT HOSPITALIZATION TO COUNTERACT MUSCLE & FUNCTION DECLINE. Mylène Aubertin-Leheudre (UQAM, Montreal, Canada)

Backgrounds: Older patients experience an accentuated loss of mobility after a hospital stay increasing the risk of falls, injuries, and hospital readmissions. However there is no current recommendation for prescribing physical activity (PA) after hospitalizations. Objectives: 1) Develop a decisional tree to systematically prescribe an individualized, adapted and non-supervised home-based PA program for older adults after hospital discharge (Preventing loss of Autonomy by Treatment Post-Hospitalization: PATH-tool); 2) investigate its feasibility and acceptability; and 3) estimate its potential effects on physical function. Methods: Population: Patients admitted to Geriatric Assessment Unit (GAU; criteria: >=65, hospital length of stay>7days, discharge to home; no contraindications for PA; understand French/English) were recruited from March to September 2017. PATH-tool: The decisional tree includes 3 sub-tests (cognitive: MMSE/cardio-strength: 30sec-chair/ SPPB balance) linked to 27 different mobility profiles and adapted PA programs based. Intervention: The PA program was performed over a 12-week period (1 session/day; 5–20 minutes each; 3–4 exercises). Results: Among 100 patients, 56 were eligible, 29 agreed to participate (52% prescription rate) and 17 completed the protocol. Most of the participants were satisfied (14/17) and enjoyed (13/17) the PA program prescribed. Most of the health professionals found it relevant to the patient (7/8) and reported no extra burden (6/8) associated with its implementation. Adherence to the PA program was 5 sessions/week. A medium-to-large effect size (Cohen’s d) was observed for the Timed Up&Go (d=1.04) and 30-sec sit-to-stand tests (d=0.75). Conclusion: This study suggests that the implementation of the PATH-tool may be feasible across GAUs, safe and acceptable from the patients’ and healthcare professionals’ perspectives in addition to lead to some benefits.

C11- PROGRESSION OF PHYSICAL FRAILTY AND THE RISK OF ALL-CAUSE MORTALITY IN THE US NATIONAL HEALTH AND AGING TRENDS STUDY: IS THERE APOINT OF NO RETURN? Qian-Li Xue1, Karen Bandeen-Roche1,2, Jing Tian1,2, Judith D. Kasper3, Linda P. Fried4((1) Center on Aging and Health, Johns Hopkins Medical Institutions, Baltimore, MD, USA; (2) Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA; (3) Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland,USA; (4) Mailman School of Public Health, Columbia University, New York, NY, USA)

Backgrounds: While frailty appears to be reversible, with progressive severity, a complete remission becomes increasingly rare in the absence of an intervention. Objectives: This study investigates: (I) whether there is a point in the progression of frailty beyond which the process becomes irreversible and death becomes imminent (a.k.a. point of no return), and (II) whether specific patterns of emergence of frailty manifestations are as relevant as the number of manifestations accumulated over time in determining the point of no return. Methods: The analysis included 2,161 non-frail older adults identified using the physical frailty phenotype who were living in the community or residential care setting at baseline in 2011 and had at least one annual follow-up visit between 2011 and 2018. We characterized the history of frailty dynamics in two ways. First, we modeled the number of incident frailty criteria (0-5, termed frailty score henceforth) as a time-varying covariate in a Cox model to explore a possible threshold relationship with all-cause mortality. Second, we examined the associations between mortality and a priori-defined patterns of *first* manifestations that include having: (a) weakness, slowness, and/or low activity first, (b) exhaustion and/or weight loss first, or (c) co-occurrence of>=1 criteria in (a) with one or both criteria in (b). We restricted this latter analysis to 1,556 who were non-frail at baseline and developed pre-frailty or frailty during the study. Results: There was a step-wise association between greater number of incident frailty criteria and increasing risk of mortality, with anotable risk acceleration after having accumulated all five criteria (HR=34.6, 95% Confidence Interval (CI)=14.6-81.9). In addition, mortality risk increased by 87% when exhaustion and/ or weight loss co-occurred with slowness, weakness, and/or low activity at the nascence of frailty manifestation (HR=1.87, 95% CI=1.30–2.68), compared with having slowness, weakness, and/or low activity first (reference) or having exhaustion and/or weight loss first (HR=1.14, 95% CI=0.80–1.62). The risk within pattern (b) was further elevated with co-occurrence of >=3 criteria (HR=3.18, 95% CI=2.01–4.96) compared to two criteria (HR=1.13, 95% CI=0.70–1.83). Conclusion: Both the number and rate/pattern of accumulation of incident frailty criteria were associated with mortality risk. On going monitoring of frailty progression could aid clinical and personal decision-making regarding timing of intervention and eventual transition from curative to palliative care.

C12- HOW CAN THE MICROBIOME PLAY A ROLE IN MUSCLE FUNCTIONALITY? Anton De Spiegeleer1,2,3, Dirk Elewaut3, Nele Van Den Noortgate1, Yorick Janssens2, Nathan Debunne2, Selien Van Langenhove2, Srinath Govindarajan3, Bart De Spiegeleer2, Evelien Wynendaele2((1) Department of Geriatrics, Faculty of Medicine and Health Sciences, Ghent University Hospital, Ghent, Belgium; (2) Drug Quality and Registration (DruQuaR) group, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium; (3) Unit for Molecular Immunology and Inflammation, VIB-Center for Inflammation Research, Ghent, Belgium)

Background: Sarcopenia, the loss of muscle mass and strength associated with ageing, leads to devastating health outcomes as loss of functionality and all-cause mortality. The pathophy siological mechanisms that might lead to sarcopenia are still poorly understood. However, recent studies as well as our in vitro and in vivo data indicate the microbes in the gut, the so-called microbiome, as a possible etiologic factor. Objectives: In this study we investigated the effects of a new class of microbial metabolites on muscle homeostasis. Methods: Extensive C2C12 muscle cell in vitro experiments and C. elegans worm in vivo experiments were conducted. Results: We will present our exciting results of a new class of microbial metabolites that influence C2C12 muscle cells and mobility of C.elegans worms. As we are currently filing a patent with our findings, these data are still confidential. Conclusion: Our findings are opening a new diagnostic and therapeutic dimension in the complex syndrome of muscle diseases, includingsarcopenia.

C13- IL-15Rα IS RESPONSIBLE FOR TRANSLOCATION OF IL-15, ANABOLIC MYOKINE, ONTO THE SKELETAL MUSCLE CELL MEMBRANE WHICH IS REQUIRED FORIL-15 SECRETION. Taku Fujimoto1, Ken Sugimoto1, Toshimasa Takahashi1,2, Yukiko Yasunobe1, Keyu Xie1, Minoru Tanaka1,3,4, Yuri Onishi1, Shino Yoshida1, Hitomi Kurinami1, Hiroshi Akasaka1, Hiromi Rakugi1((1) Department of Geriatric and General Medicine, Graduate School of Medicine, Osaka University, Japan; (2) Departments of Medicine and Physiology, University of Toronto, Canada; (3) Department of Rehabilitation Science, Graduate School of Health Sciences, Kobe University, Japan; (4) Department of Rehabilitation Science, Osaka Health Science University, Japan)

Background: Skeletal muscle is an organ responsible not only for motor function but also for 80% of glucose metabolism. Exercise increases glucose uptake in skeletal muscle and improves insulin resistance. On the other hand, myokine is a cytokine derived from skeletal muscle, and is considered as a carrier for skeletal muscle-organ linkage. We focused on Interleukin-15 (IL-15), ananabolic myokine, and reported that skeletal muscle-specific over expression of IL-15 improves skeletal muscle glucose metabolism via the AMPK pathway. It is considered essential that IL-15 binds to IL-15 receptor alpha (IL-15Rα) and moves tothe cell membrane for IL-15 secretion from leukocytes. However, there is no report about IL-15 secretion in skeletal musclecells. Objectives: The aim of this study is to investigate the effect of IL-15 receptor on intracellular localization of IL-15 in skeletal muscle cells. Methods: The vector of IL-15 tagged with GFP (IL-15-GFP) and IL-15 receptor tagged with OFP (IL-15Rα/β/γ-OFP) was transfected into C2C12 (mouse-derived skeletal muscle cells), and then C2C12 was induced to differentiate into myotube. Transfected myotube was observed with a confocal microscope. Results: IL-15-GFP was mainly expressed in the cytoplasm, and IL-15Rα-OFP was expressed on the cell membrane. When IL-15-GFP and IL-15Rα-OFP were co-transfected, IL-15-GFP expression moved onto the cell membrane. IL-15E46K-GFP, which can not bind to IL-15Rα, did not move to the cytoplasm even when co-expressed with IL-15Rα. When IL-15-GFP and IL-15Rβ-OFP orIL-15Rγ-OFP were co-expressed, almost all IL-15Rβ-OFP and IL-15Rγ-OFP were localized in the cytoplasm and did not merge with IL-15-GFP. In the presence of over expressed IL-15Rα, IL-15Rβ and IL-15Rγ merged with IL-15-GFP. Conclusion: IL-15 was shown to translocate to the cell membrane of skeletal muscle cells by binding to IL-15-Rα. This binding allows IL-15 tobind to IL-15Rβ/γ too. In order to secrete IL-15, it is considered that IL-15 forms a complex with IL-15Rα and is fused to the cell membrane. This study showed that IL-15 translocates to the cell membrane by binding to IL15-Rα even in skeletal muscle cells. IL-15Rβ/γ was expressed on the cell surface in leukocytes, but was expressed in the cytoplasm in skeletal muscle cells. Endocrine, autocrine, and juxtacrine are assumed as secretion modes of IL-15 in leukocytes. IL-15 signaling in skeletal musclecells requires further investigation.

C14- INTERACTIONS BETWEEN DIETARY PROTEIN AND AUTOPHAGY IN AGED SKELETAL MUSCLE. Gabriele Civiletto1, Claire Regard1, Philipp Gut1, Jerome N. Feige1,2((1) Nestle Research, EPFL Innovation Park, Lausanne, Switzerland; (2) School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne, Switzerland)

Background: The impact of muscle quality on functional capacity during sarcopenia is receiving increasing attention, yet the mechanisms andsolutions to target muscle function remain poorly explored. Autophagy has emerged as a prominent cellular recycling system whose activation promotes broad health benefits in the context of aging and cellular stress. Objectives: In the present study, we aimed to understand how to modulate autophagy through nutrition and to study how protein intake cross-talks with the regulation of autophagy. Methods: Using a zebrafish LC3 reporter in skeletal muscle, we screened the effect of individual amino acids and micronutrients on skeletal muscle autophagy. The crosstalk between protein intake and autophagy was then studied using dietary interventions inmice. Results: We uncovered that high protein is permissive to autophagy in skeletal muscle. While Leucine represses autophagy, other amino amino acids stimulate autophagosome formation and cellular recycling. Importantly, the anabolic effects of dietary protein supplementation can be uncoupled from the mTOR-mediated repression of autophagy through a concomitant signaling of otheramino acids to the autophagic machinery. Conclusion: Autophagy is a novel mechanism to target muscle functional capacity during aging, which can be induced by specific amino acids and natural bioactives. Importantly, high protein is permissive to autophagy induction in skeletal muscle, paving the way tonovel nutritional concepts combining the anabolic effects of protein with natural autophagy inducers.

C15- GERAS DANCE (DANCING FOR COGN