OC1- THE APELIN RECEPTOR AGONIST BGE-105 PREVENTS MUSCLE ATROPHY INDUCED BY BED REST IN HEALTHY VOLUNTEERS AGED ≥ 65 YEARS. Ann Neale(1), Eric Wang(1), Eric Morgen(1), Kristen Fortney(1), Patrick Martin(1), Kristen Reiman(1), Paul Rubin(1), William Evans(2) ((1) BioAge Labs, Richmond, CA, USA; (2) Nutrition Sciences & Toxicology, University of California Berkeley, CA, USA)

Background: The apelin peptide promotes regeneration and repair of skeletal muscle. BioAge’s AI-driven analysis of human aging profiles revealed that people with higher apelin pathway activity as they age live longer and healthier lives. Loss of apelin activity with age is correlated with multiple morbidities. Objectives: BioAge tested the small molecule BGE-105, an apelin receptor agonist, in a Phase 1b clinical trial for prevention of muscle atrophy in older people. Methods: Healthy volunteers 65 or older were subjected to a 10-day course of strict bed rest, during which they received daily intravenous infusions of BGE-105 (n=11) or placebo (n=10). Thigh circumference, ultrasound measurements of the vastus lateralis, Goutallier grade (an index that quantifies fatty degeneration in muscle), and muscle protein synthesis were recorded before and after bed rest. Results: Bed rest resulted in muscle atrophy on day 10 of the study. BGE-105 improved all muscle parameters relative to placebo: thigh circumference (placebo: −6.4% vs. baseline; BGE-105: +0.8% vs baseline; p < 0.001), vastus lateralis diameter (placebo: −21.2%; BGE-105: −5.7%; p < 0.01); and vastus lateralis cross-sectional area (placebo: −19.5%; BGE-105: −8.0%; p < 0.05). Goutallier grade worsened in 8 of 10 volunteers on placebo vs. 1 of 11 volunteers receiving BGE-105 (p < 0.005). Bed rest decreased synthesis of muscle proteins, and this effect was significantly ameliorated by BGE-105 (placebo: 15.9%; BGE-105: 22.0%; p < 0.005). All percentages are relative to baseline before initiation of bed rest. No severe adverse effects were observed. Conclusion: Daily treatment with BGE-105 significantly improved multiple metrics of muscle atrophy in healthy older people on bed rest. BGE-105 may have prevented reductions in muscle dimensions by increasing the rate of muscle protein synthesis. Diseases associated with muscle atrophy, including acute myopathies in mechanically ventilated ICU patients and chronic illnesses driven by progressive loss of muscle function with age, affect millions of people each year. Given that there are no effective therapies for diseases of muscle aging, the trial data warrant further clinical investigation of BGE-105 for acute and chronic indications.

OC2- IMPACT OF L-CITRULLINE SUPPLEMENTATION AND LOW-INTENSITY RESISTANCE TRAINING ON LEG ENDOTHELIAL FUNCTION, LEAN MASS, AND STRENGTH IN POSTMENOPAUSAL WOMEN WITH HYPERTENSION. Arturo Figueroa(1), Arun Maharaj(2), Stephen M. Fischer(1), Katherine N. Dillon(1), Mauricio A. Martinez(1), Yejin Kang(1) ((1) Department of Kinesiology and Sport Management, Texas Tech University, Lubbock, TX, USA; (2) Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, Memphis, TN, USA)

Background: Sarcopenia is associated with reduced endothelial function (flow-mediated dilation [FMD]) and hypertension. L-citrulline (CIT), an arginine and nitric oxide precursor, has improved blood pressure in hypertensive women and lean mass (LM) in malnourished older women. Low-intensity resistance training (LIRT) has increased strength but not LM in older women. CIT supplementation combined with aerobic training increased muscle strength but not LM in dynapenic older adults. Objectives: The aim of this study was to test the hypothesis that CIT supplementation combined with LIRT would have additive benefits on leg endothelial function, LM, and muscle strength in postmenopausal women with hypertension. Methods: Twenty-four postmenopausal women aged 50–75 years were randomized to either 10g/day of CIT (n= 13) or placebo (PL, n= 11) alone for 4 weeks and combined with LIRT (CIT+LIRT or PL+LIRT) for another 4 weeks. Leg endothelial function was measured using superficial femoral FMD. Leg LM was measured using DEXA. Muscle strength was measured using leg curl 10RM. LIRT consisted of 3 sets of four leg exercises at 40–50% of 1RM, 3 days/week. Measurements were performed at 0, 4, and 8 weeks. Results: CIT supplementation increased FMD compared to PL after 4 weeks (CIT:1.8±0.3% vs. PL:−0.2±0.5%, P=0.004) and 8 weeks (CIT+LIRT:2.7±0.5% vs PL+LIRT:−0.02±0.5, P=0.003). CIT alone for 4 weeks did not improve leg LM or strength. CIT+LIRT increased leg LM compared to PL+LIRT (0.5±0.2 kg vs 0.1±0.1 kg, P=0.046). The increase in leg curl strength from baseline was greater after CIT+LIRT compared to PL+LIRT (6.9±0.9 kg vs. 3.3±0.9 kg, P=0.04). There was a significant correlation between changes in FMD and leg LM (r= 0.44, P= 0.03) but not with changes in leg strength (r= 0.32, P= 0.13) during the combined interventions. Conclusion: CIT supplementation alone for 4 weeks improved leg endothelial function but not leg LM and strength. CIT supplementation had and additive effect on leg muscle strength. Our findings suggest that CIT supplementation combined with LIRT induced greater increases in leg LM via improved endothelial function in postmenopausal women with hypertension.

OC3- LIVING LONGER BUT FRAILER? TRENDS IN LIFE EXPECTANCY AND FRAILTY IN OLDER SWEDISH ADULTS. Clare Tazzeo(1), Debora Rizzuto(1,2), Amaia Calderón-Larranaga(1,2), Serhiy Dekhtyar(1,2), Alberto Zucchelli(1,3), Xin Xia(1), Laura Fratiglioni(1,2), Davide Liborio Vetrano(1,2) ((1) Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden; (2) Stockholm Gerontology Research Center, Stockholm, Sweden; (3) Department of Information Engineering, University of Brescia, Brescia, Italy)

Background: Frailty — a clinical syndrome characterized by physiological vulnerability to stressors — is one of the greatest threats to healthy aging. However, it is unclear whether there has been an expansion or compression of frailty over time with increases in life expectancy. Objectives: This study aims to: 1) examine frailty state transitions by birth year, and 2) assess whether there has been an expansion or compression of years of life spent frail across birth cohorts. Methods: We analyzed approximately 15 years of follow-up data from 2941 individuals, aged 60+ years, participating in the Swedish National study on Aging and Care in Kungsholmen (SNAC-K; baseline 2001–2004). A 40-deficit frailty index (FI) was built, and three frailty states were identified: robust (FI ≤ 0.125), mild frailty (0.125 < FI ≤ 0.25), and moderate & severe frailty (FI > 0.25). Multi-state survival analyses were implemented to compute frailty-state transitions; hazard ratios for the transitions were obtained with birth year and sex as predictors, also adjusting for age. Frailty state-specific life expectancies for robust persons at age 60 were estimated by birth cohort and sex. Results: Forecasted life expectancy increased, but a greater proportion of life was spent frail, in later birth cohorts. Hazards of transitioning from mild frailty to death (hazard ratio [HR]: 0.89; 95% confidence interval [CI]: 0.83–0.97) and moderate and severe frailty to death (HR: 0.98; 95% CI: 0.97–0.99) were lower with later birth year. Unfavourable transitions from robust to mild frailty (HR: 0.81; 95% CI: 0.70–0.93), mild frailty to moderate and severe frailty (HR: 0.80; 95% CI: 0.68–0.93), and moderate and severe frailty to death (HR: 0.68; 95% CI: 0.59–0.78) were less likely among women. Women had a greater predicted life expectancy than men, but more time was spent frail; this difference attenuated over time. Conclusion: Our results point to an expansion of frailty in older Swedish adults and an attenuation in discrepancies in life expectancy by sex. As population aging continues, it is more important than ever that we continue to monitor frailty trends to inform resource allocation and preventive strategies that promote resiliency and independence in older adults.

OC4- IDENTIFICATION OF BIOMARKERS OF FRAILTY IN SILICO. Kristina Tomkova, Adewale Adebayo, Gavin Murphy, Marcin Wozniak (Department of Cardiovascular Sciences, University of Leicester, Leicester, UK)

Introduction: Frailty is a syndrome characterised on a symptomatic level by loss of muscle mass, weakness, low energy levels and overall vulnerability to stressors. However, the lack of a molecular definition of frailty presents a barrier for researchers and clinicians in developing effective interventions or specialised care for patients suffering from this syndrome. Objectives: This study aimed to identify gene expression signatures and potential biomarkers characteristic of frailty. Methods: Transcriptomic profiles from frail, non-frail, old and young individuals were retrieved from the NCBI Gene Expression Omnibus repository using E-utilities. Differential gene expression analysis was performed using the LIMMA pipeline, gene set enrichment analysis using Reactome annotations, highly correlated genes were identified using weighted correlation network analysis, and a random forest algorithm was used to identify the most discriminatory transcripts. Results: Ten studies with 553 individual samples, each examining 13 991 genes, were included. This data comprised of 315 peripheral blood mononuclear cell (PBMC) samples, 28 CD8 cell samples, and 209 muscle tissue samples. Genes involved in nucleolar processes, mitochondrial function, translation and muscle contraction were most affected in samples from frail patients (FDR < 0.001). Small nucleolar RNAs (SNORDs) were the most discriminatory and predicted frailty with high accuracy. The results also indicated that frailty is an independent phenomenon compared to biological ageing. Old age affected a wide variety of pathways including protein translation, immunity, and cell cycle, while frailty affected a more specific portfolio of pathways revolving around nucleolar processes, mitochondrial function and muscle contraction. Further analysis indicated that frailty might be tissue specific. Conclusion: Our results suggest that nucleolar processes, including ribosomal assembly, mainly driven by SNORDs, are potentially a frailty-specific mechanism that likely lead to dysregulation of mitochondrial function and changes in the expression of muscle proteins.

OC5- ASSOCIATION BETWEEN DEPRESSIVE SYMPTOMS AND FRAILTY BY DIFFERENT PHYSICAL ACTIVITY LEVELS IN EUROPEAN COMMUNITY-DWELLING OLDER ADULTS ENROLLED IN THE DO-HEALTH TRIAL — A THREE-YEAR PROSPECTIVE OBSERVATIONAL ANALYSIS. Michael Gagesch(1,2), Stephanie Gängler(1,2), Michèle Mattle(1,2), Reto W. Kressig(3), Bruno Vellas(4), Gregor Freystätter(1,2), Heike A. Bischoff-Ferrari(1,2,5) for the DO-HEALTH investigators ((1) Department of Aging Medicine and Aging Research, University Hospital Zurich and University of Zurich, Zurich, Switzerland; (2) Centre on Aging and Mobility, University Hospital Zurich, City Hospital Zurich Waid and University of Zurich, Zurich, Switzerland; (3) University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland; (4) Gérontopôle, Toulouse University Hospital, University of Toulouse, UMR INSERM 1027, Toulouse, France; (5) University Clinic for Acute Geriatric Care, City Hospital Waid and Triemli, Zurich, Switzerland)

Background: Mechanisms leading to frailty root in multi-system dysregulations. In addition, mental health has been associated with an increased frailty risk. Prior studies indicate a bidirectional association of frailty and depressive symptoms. However, longitudinal data as well as data on potential modifiers including physical activity (PA) and sedentary behavior (SB) are limited. Objectives: We aim to investigate a) the association of baseline depressive symptoms (DS) in robust participants with incident pre-frailty/frailty over 3 years, and b) the association of change in DS from baseline to year 3 with time, and the incidence of pre-frailty/frailty in the same timeframe. Additionally, we will investigate these associations stratified by different baseline PA and SB levels. Methods: This is a prospective observational analysis of 1,137 DO-HEALTH participants robust at baseline (mean age, 74.3 years; 56.5% women, mean gait speed 1.18 m/s). DO-HEALTH is a multi-center clinical trial in community-dwelling European adults aged 70+. We operationalized frailty by the Fried physical frailty phenotype (robust/pre-frail/frail). DS were assessed with the Geriatric Depression Scale 15 items (GDS-15). Levels of PA and SB were classified based on the Nurses’ Health Study Physical Activity Questionnaire. Results: We will present population characteristics overall and by DS status at baseline. To report the association of baseline GDS-15 scores and incident pre-frailty/frailty we will present odds ratios and 95% confidence intervals from a generalized estimating equation model for repeated binary outcomes for each outcome after adjustments. Predefined adjustments are age, sex, BMI, study center, cognitive function, presence of pain, use of antidepressant drugs, faller status at baseline, DO-HEALTH treatments, time, and their interaction. A stratified analysis by level of PA and SB will be performed, i.e. meeting WHO PA guidelines vs. not meeting WHO PA guidelines; and high vs. low reporting of sedentary behavior. Conclusion: Our analysis aims to contribute important knowledge on the association of incident pre-frailty/frailty and DS at baseline and DS change over three years of follow up in generally healthy participants aged 70+, recruited from five European countries. Additionally, novel data on the influence of different levels of PA and SB on the exposure-disease relationship will be discussed.

OC6- ASSOCIATION BETWEEN THE SEVERITY OF THE DISEASE AND THE RISK OF SARCOPENIA IN PEOPLE WHO RECOVERED FROM COVID-19. Ester Wiggers(1), Gabriel Peinado Costa(2), Paulo Giusti Rossi(3), Átila Alexandre Trapé(2) ((1) Geriatric Department, University of São Paulo, Ribeirão Preto, São Paulo, Brazil; (2) School of Physical Education and Sport of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil; (3) Department of Physical Therapy, Federal University of São Carlos, São Carlos, Brazil)

Background: Some studies have investigated the relationship between anthropometric variables, such as body mass index and waist circumference, with the severity of COVID-19. However, more specific body composition assessments, such as the one performed through Dual-energy X-ray absorptiometry (DXA), have yet to be explored to study the relationship with the severity of COVID-19. Objectives: To verify the association between the severity of COVID-19 and the risk of sarcopenia in recovered COVID-19 patients. Methods: Descriptive and cross-sectional study. Volunteers (aged 30–69 years old) were selected from the community between September and October 2020, about 30 days after recovery from clinical signs or medical discharge. We assessed body composition at baseline by DXA, with the measurement of the skeletal mass index (SMI), physical fitness by 30-s chair stand (CS), and agility and dynamic balance (AGI). Information related to sex and age was collected. COVID-19 severity was classified into four categories: mild: common flu-like symptoms without dyspnea (n=16), moderate: common flu-like symptoms with dyspnea (n=49), severe: hospitalization (n=10), and critical: hospitalization with intensive care (respirator) (n=8). The risk of sarcopenia was classified following the criteria of Janssen et al. into three categories: regular grade, grade 1 risk, and grade 2 risk. Quantitative variables are presented as mean (standard deviation), and categorical variables are presented as relative frequency. The association has been verified by Fisher’s exact test, and correlation strength was verified through Pearson (continuous variables) and Spearman (discrete variables), with a 5% significance level. Results: The sample consisted of 83 participants aged 48.5(9.8) without a difference (p>0.05) between groups. An association between COVID-19 severity and sarcopenia risk could be observed (χ2=13.5; df=3; p<0.05), as severity mild, moderate, severe, and critical had 24.5%, 70.7%, 2.4%, and 2.4% for no risk of sarcopenia, respectively, versus 14.3%, 47.6%, 21.4%, and 16.7% for grade 1 sarcopenia risk. Additionally, CS (number of repetitions) correlated positively (r=0.49), and AGI (time to complete the circuit) correlated negatively (r=−0.54) to SMI. Conclusion: The COVID-19 severity was associated with SMI classification, with severity 3 and 4 more frequent for grade 1 sarcopenia risk. Additionally, the SMI score correlated moderately with physical fitness. Keywords: sarcopenia, COVID-19, body composition.

OC7- BIOCHEMICAL MARKERS OF MUSCULOSKELETAL HEALTH AND AGING TO BE ASSESSED IN CLINICAL TRIALS OF DRUGS AIMING AT THE TREATMENT OF SARCOPENIA. Aurélie Ladang(1), Charlotte Beaudart(2), Jean-Yves Reginster(2,3), Nasser Al-Daghri(3), Olivier Bruyère(2), Nansa Burlet(2), Matteo Cesari(4,5), Antonio Cherubini(6), Mario Coelho da Silva(7), Cyrus Cooper(8), Alfonso J. Cruz-Jentoft(9), Francesco Landi(10), Andrea Laslop(11), Stefania Maggi(12), Ali Mobasheri(2,13–15), Sif Ormarsdottir(16), Régis Radermecker(17), Marjolein Visser(18), Maria Concepcion Prieto Yerro(19), René Rizzoli(20), Etienne Cavalier(1) ((1 Department of clinical chemistry, CHU de Liège, University of Liège, Liège, Belgium; (2) WHO Collaborating Center for Public Health aspects of musculo-skeletal health and ageing, Division of Public Health, Epidemiology and Health Economics, University of Liège, Belgium; (3) Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia; (4) Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; (5) Geriatric Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; (6) Geriatric Unit, IRCCS Istituti Clinici Scientifici Maugeri, Milan, Italy; (7) Laboratory of Clinical and Therapeutical Pharmacology, Portugal; (8) MRC Lifecourse Epidemiology Unit, University of Southampton UK; (9) Servicio de Geriatría. Hospital Universitario Ramón y Cajal (IRYCIS). Madrid, Spain; (10) Department of Geriatrics, Neurosciences and Orthopedics, Catholic University of the Sacred Heart, Rome, Italy; (11) Scientific Office, Federal Office for Safety in Health Care, Vienna, Austria; (12) CNR Aging Branch-IN, Padua, Italy; (13) State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania; (14) Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland; (15) Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; (16) Landspitali, University Hospital of Iceland, Reykjavik, Iceland; (17) Department of Diabetes, Nutrition and Metabolic Disorders, Clinical Pharmacology, University of Liege, CHU de Liège, Liège, Belgium; (18) Vrije Universiteit Amsterdam, Department of Health Sciences, Amsterdam, the Netherlands; (19) Agencia Española de Medicamentos y Productos Sanitarios, Madrid, Spain; (20) Service of Bone Diseases, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland)

Background: In clinical trials, biochemical markers provide useful information on drug’s mode of action, on therapeutic response and side effect monitoring, and can act as surrogate endpoints. In pharmacological intervention development for sarcopenia management, there is an urgent need to identify biomarkers that should be measured in clinical trials and could be used in the future in clinical practice. Objective: The objective of this consensus report is to provide a clear list of biochemical markers of musculoskeletal health and ageing that can be recommended to be measured in Phase II and Phase III clinical trials evaluating new chemical entities for sarcopenia treatment. Methods: The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Disorders (ESCEO ASBL) jointly with the Centre Académique de Recherche et d’Expérimentation en Santé (CARES SRL) organized in September 2022, under the auspices of the World Health Organization Collaborating Center for Epidemiology of Musculoskeletal Health and Aging, a working group including scientists, specialists in Laboratory medicine and clinicians expert in the field of biochemical markers and sarcopenia as well as representatives of the regulatory bodies. Following a systematic literature review on the existing evidences, all experts met during a face-to-face meeting to discuss and agree on recommendations. Results: the group proposed to classify biochemical markers into 2 series: biochemical markers evaluating musculoskeletal status and biochemical markers evaluating causal factors. For series 1, the group agreed on 4 biochemical markers that should be assessed in Phase II or Phase III trials (i.e. Myostatin-Follistatin, Brain Derived Neurotrophic Factor, N-terminal Type III Procollagen and Serum Creatinine to Serum Cystatin C Ratio — or the Sarcopenia Index). For series 2, the group agreed on 6 biochemical markers that should be assessed in Phase II trials (i.e. the hormones Insulin-like growth factor-1 (IGF-I), dehydroepiandrosterone sulfate, and cortisol, and the inflammatory markers C-reactive protein (CRP), interleukin-6 and tumor necrosis factor-α), and 2 in Phase III trials (i.e. IGF-I and CRP). The group also proposed optional biochemical markers that may bring insights on the mode of action of pharmacological therapies. Conclusion: Further research and development of new methods for biochemical marker assays may lead to the evolution of these recommendations.

OC8- ASSOCIATION BETWEEN THYROID FUNCTION AND LOWER LIMB COMPOSITION IN OLDER ADULTS: ANALYSIS FROM THE BALTIMORE LONGITUDINAL STUDY OF AGING. Hamza Ibad(1), Shadpour Demehri(1), A. Zenobia Moore(2), Eleanor M Simonsick(2), Jennifer SR Mammen(3) ((1) Johns Hopkins University School of Medicine, Department of Radiology, Baltimore MD, USA; (2) National Institute on Aging, National Institutes of Health, Baltimore MD, USA; (3) Johns Hopkins University School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Baltimore MD, USA)

Background: In older adults, higher thyroid hormone levels have been associated with slower gait speed, lower endurance and higher fatigability. As thyroid hormone is catabolic, higher levels have the potential to accelerate age-related functional decline including loss of muscle mass and development of sarcopenia. Furthermore, thyroid hormone treatment is the most common cause of thyroid hormone excess. Therefore, any negative impact of higher thyroid hormone levels on sarcopenia would have implications for the clinical use of thyroid hormone replacement in older adults and especially in those with frailty. Objectives: Investigate the association between thyrotropin (TSH) and thyroid hormone levels and lower limb composition measured by dual-energy X-ray absorptiometry (DEXA) in participants of the Baltimore Longitudinal Study of Aging (BLSA). Method: Clustered-robust standard errors linear regression models were used to estimate crosssectional relationships between visit-specific thyroid function tests and lower limb composition, adjusted for levothyroxine use, age, race, sex, BMI, smoking, alcohol intake, total cholesterol, systolic blood pressure, and self-reported history of type II diabetes mellitus or knee osteoarthritis. Results: 1168 participants, 51% female and 73% white, made a total of 4669 eligible visits between 2003 and 2019, with 63.8% of participants making at least 3 visits. Mean age across all observations was 78 years, and levothyroxine (LT4) was in use for thyroid hormone replacement at 14% of visits. Knee osteoarthritis was reported at 36% of visits. Mean TSH was 2.4 mU/L and mean Free T4 (FT4) was 1.0 ng/dL. FT4 was negatively associated with lean mass (beta: −118.57, p-value <0.01) and positively associated with fat mass (beta: 98.16, p-value < 0.01) in fully adjusted models. Excluding visits at which participants were on LT4 did not change the associations between FT4 and body composition (FT4 and lean mass beta: −143.33, p-value <0.001). Neither TSH nor Free T3 were significantly associated with body composition. Conclusion: The association between higher FT4 and lower lean and higher fat mass suggests that higher thyroid hormone levels maybe a modifiable risk factor for sarcopenia that warrants further investigation. Prospective studies with a sufficient exposure time-frame are needed to assess for causality

OC9- AGING TRANSCRIPTOMIC SIGNATURES OF HIGH INTENSE EXERCISE AFFECTING MUSCLE BIOENERGETICS. Stefano Donega(1), Nirad Banskota(1), Julian Candia(1), Yulan Piao(1), Chee Chia(1), Supriyo De(1), Ranjan Sen(1), Luigi Ferrucci(1) ((1) National Institute on Aging, National Institutes of Health, Baltimore, MD, USA)

Background: Mitochondrial mass and function decline with aging in humans and such decline affects many biological processes, in particular the capacity of organisms to expand the proteome in response to exterior stimuli or unfavorable metabolic conditions. There is evidence that some of these molecular changes involve the production of alternative RNA splicing variants, either directly or indirectly in response to those that modulate master regulators of the energy crisis response, namely AMPK. Mechanisms that maintain an optimal steady-state level of ATP are only partially understood but there is initial evidence in multiple model species that while mitochondrial mass and function decline with age, compensatory mechanisms are activated including alternative splicing. Objectives: Skeletal muscles require high amount of energy to function properly and muscle tissue is an ideal model to understand changes that occur in the absence and in the presence of sufficient energy availability. Methods: The Genetic and Epigenetic Signatures of Translational Aging Laboratory Testing (GESTALT), a cross-sectional study that investigated relationships between aging and biomarkers of human blood/tissue, enrolled healthy individuals dispersed over a wide age-range (n=92, age 22–89). In this study, we investigated the relationship between muscle bioenergetics — measured by skeletal muscle oxidative capacity (kPCr) using 31P magnetic resonance spectroscopy — and the emergence of splicing variants. Results: In fully adjusted regression models, transcripts enriched for mitochondria- and respirasome- processes were lower at older ages and were higher in individuals with high mitochondrial function estimated by KPCr. Interestingly, when we compared the aging transcriptome in donors with low and high mitochondrial function — we detected pre-mRNA pathways to be up-regulated in poorer mitochondrial function donors, indicating possible key-role for specific mRNA isoforms governing muscle damage homeostasis with age. Conclusion: The association between spliceosome transcripts and age were substantially more evident in those individuals with low mitochondrial function (low kPCr) that in those with high mitochondrial function (high kPCr). We are currently investigating possible interactions with RNA subtype regulatory elements such lncRNAs, circRNAs and miRNAs, as well as contribution of Transposable Elements (TEs) and Epigenetic changes, since methyltransferase activity has been previously shown to be affected by physical activity.

OC10- BIOPHYTIS BIO101: A CANDIDATE TREATMENT FOR LONG COVID AFTER HOSPITALIZATION? Cendrine Tourette(1), Waly Dioh(1), Sandrine Rabut(1), Mounia Chabane(1), Serge Camelo(1), Myriem Louze(1), Jean Mariani(1,2), Rob Van Maanen(1), Stanislas Veillet(1) ((1) Biophytis — Sorbonne Université, BC9, Paris, France; (2) Sorbonne Université, CNRS — Institute de Biologie Paris Seine (UMR B2A), Paris, France)

Background: BIO101 (20-hydroxyecdysone) is an investigational product that activates Mas receptor (MasR), part of the renin-angiotensin system (RAS), downstream of the SARS-CoV-2 virus receptor (ACE2) and involved in several protective pathways including muscle metabolism and structure. Objectives: Assessment of safety and efficacy of BIO101 treatment in 2 vulnerable populations: sarcopenic seniors and hospitalized severe COVID-19 patients. Methods: SARA-INT was a randomized three-arm interventional study (BIO101 175 mg or 350 mg bid / placebo) with planned treatment duration of 6 Months (up to 9 months in 50 subjects). Eligibility criteria for sarcopenia: meeting FNIH criteria and SPPB score ≤ 8/12 in community-dwelling seniors. Primary endpoint was the 400-meter walking test (400MWT), secondary endpoints being other physical activity assessments. COVA trial was a randomized, placebo-controlled phase 2/3 trial. Hospitalized adults ≥45 years with respiratory decompensation due to SARS-CoV-2 were randomized 1:1 to placebo or BIO101 (350 mg bid), up to 28 days or endpoint. Primary endpoint was proportion of patients dying or requiring high-flow oxygen, mechanical ventilation or ECMO; key secondary endpoint was proportion of patients recovered and discharged; both analysed using Cochran-Mantel-Haenszel (CMH) test. Results: Besides the promising results of SARA-INT, COVA included 233 participants in the ITT population (63.5% male, mean age 62.8 years). Primary (CMH) analysis at day 28 showed a statistically significant difference favouring BIO101 (BIO101: 15.8%, placebo: 26.0%), adjusted difference -11.4% (p=0.042), a relative risk (RR) reduction of death or respiratory failure of 44.0%. Kaplan-Meier (KM) analysis of difference in proportion of patients with death or respiratory failure over 28 days was nominally statistically significant favouring BIO101 at day 28 (10.9%, p=0.023), a 45.0% RR reduction. In both studies, safety and tolerability of BIO101 was very good: less patients treated with BIO101 350mg bid experienced adverse events (AEs) compared to placebo. Conclusion: BIO101(20E), targeting the MasR, is a candidate to treat vulnerable populations (sarcopenic seniors and severe hospitalized COVID-19 patients), with meaningful efficacy data and very good safety profile at the dose of 350 mg bid and may be a potential pharmacological strategy against physical performance deterioration associated with COVID-19.

OC11- DESIGN, METHODS AND PRELIMINARY FINDINGS FOR THE ENGAGE TRIAL: AN EXERCISE AND SOCIAL ENGAGEMENT INTERVENTION FOR MULTIMORBID, HOMEBOUND AFRICAN AMERICAN OLDER ADULT-CARE PARTNER DYADS DELIVERED OVER VOICE-ACTIVATED TECHNOLOGY. Megan Huisingh-Scheetz(1), Brittni Bryant(1), Corliss Taylor(1), Brandon Foster(1), Brad Appelhans(2), Marshini Chetty(1), Margaret Danilovich(3), Elizabeth Davis(2), Nicolas Feamster(1), Laura Finch(4), Marc Richardson(1), Nikita Thomas(1), Kelly Wagman(1) Wen Wan(1), Jocelyn Wilder(4), Louise Hawkley(4) ((1) University of Chicago, Chicago, IL, USA; (2) Rush University, Chicago, IL, USA; (3) Center for Jewish Elderly, Chicago, IL, USA; (4) NORC at the University of Chicago, Chicago, IL, USA)

Background: Physical activity is essential for all age groups, across all comorbidities and geriatric syndromes; it has been described as the ‘ideal’ intervention for aging. Multimorbidity is more severe and more prevalent among African-Americans (AA) over their lifespan and they experience more accelerated aging than any other race in the US. Multimorbid OAs face increasing challenges to maintaining activity over time: disrupted physiology; required assistance to leave the home; reliance on care partners (CPs) with limited training; and restricted reimbursement for in-home exercise services. Increasing activity among homebound, multimorbid, AA OAs requires a shift in interventions to target the older adult-care partner (OA-CP) dyad and to test innovative vehicles for remote intervention delivery. EngAGE was co-developed through iterative participatory design and previously piloted. Objective: Our objective is to conduct a randomized efficacy trial of EngAGE in multimorbid, AA, homebound OAs and their CPs. Methods: The EngAGE trial is a multisite randomized controlled trial designed to compare an exercise and social engagement intervention delivered over a voice-activated device (EngAGE) or on paper in n=124 AA, multimorbid OA-CP dyads in northeast Illinois. The intervention phase will last 6 months. Older adults are eligible if they score 3–8/12 on the Short Physical Performance Battery (SPPB). WiFi hotspots are provided when needed. Primary outcomes include lower and upper extremity strength and frequency of social contact. Secondary outcomes include the SPPB score, frailty phenotype, disability and relationship quality. We will assess individual, interpersonal and community-level moderators and will ascertain perceived barriers and facilitators to intervention use. Results: Recruitment began in October 2022; n=10 dyads have been enrolled and randomized as of January 2023. Most OAs are women (n=9); the mean age is 76.4 years. All 10 OAs scored a 0 or 1/4 on the SPPB chair subscale (mean performance time 23.5 seconds). Mean maximum grip strength among OAs is 23.5 kg. All CPs (n=10) are also African-American with a mean age of 61.6 years; 5 are women. Conclusion: This trial will evaluate whether EngAGE represents an effective, user-friendly, scalable approach to improving long-term exercise and social engagement for vulnerable AA OA-CP dyads. Trial registration: ClinicalTrials.gov NCT05337514

OC12- EFFECTS OF A 12-WEEK VIVIFRAIL EXERCISE PROGRAM ON INTRINSIC CAPACITY AMONG FRAIL COGNITIVELY IMPAIRED COMMUNITY-DWELLING OLDER ADULTS: SECONDARY ANALYSIS OF A MULTICENTER RANDOMIZED CLINICAL TRIAL. Juan Luis Sánchez-Sánchez(1,2,3), Philipe de Souto Barreto(1,4), Iván Antón-Rodrigo(5,6), Fernanda Ramón- Espinoza(7), Itxaso Marín Epelde(7), Marina Sánchez-Latorre(7), Debora Moral Cuesta (7) Alvaro Casas-Herrero(7,8,9) ((1) Gérontopôle de Toulouse, Institut du Vieillissement, Centre Hospitalier Universitaire de Toulouse, Toulouse, France; (2) MOVE-IT Research Group, Department of Physical Education, Faculty of Education Sciences, University of Cadiz, Cadiz, Spain; (3) Universidad Pública de Navarra (UPNA), Pamplona, Spain; (4) CERPOP, Inserm 1295, Université de Toulouse, UPS, Toulouse, France; (5) Hospital of Eibar, OSI Debabarrena. Osakidetza. Gipuzkoa, Spain; (6) Grupo de Investigación en Atención Primaria. Biodonostia Institute of Health Research. San Sebastián. Gipuzkoa. Spain; (7) Geriatric Department, Hospital Universitario de Navarra (HUN), Pamplona, Spain; (8) Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNA, Pamplona; (9) CIBER of Frailty and Healthy Aging (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain)

Introduction: The World Health Organization (WHO) recently defined the construct of intrinsic capacity (IC), a function-based marker of older adult’s health encompassing all mental and physical capacities of the individual. Multicomponent physical exercise (MCE) is a potential intervention capable to maintain/increase IC at older age; however, evidence is scarce on the effects of MCE on IC in cognitively impaired pre-frail/frail older adults. Methods: Secondary analyses of a randomized clinical trial. 188 older outpatients (age=84.06±4.77, 70.2% women) presenting with pre-frailty/frailty (according to Fried Criteria) and mild-cognitive impairment/mild-dementia were recruited in the Geriatric clinics of 3 tertiary hospitals in Spain. Subjects were randomized to participate in the 12-week home-based individualized Vivifrail MCE or usual care. An IC index was created based on the z-score of the locomotion (Short Physical Performance Battery), cognitive (Montreal Cognitive Assessment), psychology (15-item GDS Yesavage) and vitality (handgrip strength) domains. Results: After the 3-month intervention, linear mixed models showed significant between-group differences in the evolution of the IC composite score (β=0.48; 95% CI=0.24, 0.74; p<0.001), IC Locomotion (β=0.42; 95% CI=0.10, 0.74; p<0.001), IC Cognition (β=0.45; 95% CI=0.03, 0.87; p<0.05) and IC Vitality domains (β=0.50; 95% CI=0.25, 0.74 at 3-month) favoring the MCE group. Conclusion: The 12-week Vivifrail multicomponent exercise program is an effective strategy to enhance IC, especially in terms of locomotion, cognition, and vitality IC domains in community-dwelling older adults with pre-frailty/frailty and MCI/mild-dementia, compared to usual care.

OC13- BODY FAT MASS MEDIATES THE EFFECT OF INSULIN RESISTANCE ON FUNCTIONAL DECLINE BUT NOT ON MORTALITY IN A COMMUNITY-DWELLING OLDER ADULTS: RESULTS FROM TOLEDO STUDY OF HEALTHY AGING. Mariam El Assar(1,2), Javier Angulo(2,3), Jose A Carnicero-Carreño(1,2), Patricia Sosa(1), Alejandro Álvarez-Bustos(2), Francisco J García-García(2,4), Leocadio Rodríguez-Mañas(2,5) ((1) Fundación de Investigación Biomédica, Hospital Universitario de Getafe, Getafe, España; (2) Centro de Investigación Biomédica en Red sobre Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, España; (3) Servicio de Histología-Investigación, Unidad de Investigación Traslacional en Cardiología (IRYCIS-UFV), Hospital Universitario Ramón y Cajal, Madrid, Spain; (4) Servicio de Geriatría, Hospital Virgen del Valle, Toledo, España; (5) Servicio de Geriatría, Hospital Universitario de Getafe, Getafe, España)

Background: Recent evidence suggests that insulin resistance (IR) is a risk factor for functional decline meanwhile it protects from mortality in non-diabetic older adults. Both age-related outcomes seem to be associated with body composition. Objectives: We aim to assess the potential role of body composition in the association of IR with functional decline and with mortality risk in older subjects. Methods: 1,114 non-diabetic subjects from the Toledo Study of Healthy Ageing cohort were included (mean age 74.56±5.73; 56.10% female). IR was determined by the homeostasis model assessment index (HOMA-IR) at baseline while frailty was assessed by the Frailty Trait Scale-5 (FTS5) at baseline and after a median follow-up period of 2.99 years. The functional decline during follow-up was determined as the worsening in 2.5 points for the FTS5 score. Deaths were also registered (6.31 years median follow-up). Body compositions were determined using Dual-Energy X-ray absorptiometry. Multivariate regression models were used to analyze the effects of HOMA-IR on outcomes. Age, gender, and Charlson index were included in basic adjustment model while fat and lean mass were included as potential confounding variables. Results: HOMA-IR increased the risk of functional decline in FTS5 after basic adjustment (OR 1.44 [1.11–1.86], p=0.0056). This significant association was lost when further adjusted by total fat mass (OR 1.15 [0.88–1.52], p= 0.3046). Meanwhile, when controlling for lean mass, HOMA-IR was still able to predict incident worsening in FTS5 (OR 1.40 [1.07, 1.82], p= 0.01416). By contrast, HOMA-IR was inversely associated with mortality risk after basic adjustment (HR 0.67 [0.50–0.88], p=0.0043). Adjustment by total fat mass or by total lean mass did not modify the association (HR 0.72 [0.53–0.97], p= 0.0324; HR 0.67 [0.50–0.89], p= 0.0059 for fat mass and lean mass respectively). Conclusion: Fat mass but not lean mass mediates the associations of IR with functional decline but not with mortality in non-diabetic older adults. The present work was funded by grants from the Spanish Ministry of Economy, Industry and Competitiveness, cofinanced by the FEDER Funds (Instituto de Salud Carlos III, PI20/00977) and CIBERFES (CB16/10/00464), and el Proyecto MITOFUN, Fundación Francisco Soria Melguizo.

OC14- COGNITIVE STATUS AS A PREDICTOR OF BODY COMPOSITION PROFILES: A LATENT CLASS ANALYSIS. John A. Batsis(1,2,3), David H. Lynch(1), Annie Green Howard(2,3), Hsiao-Chuan Tien(3), Hillary Spangler, Shufa Du(3,4), Bing Zhang(5), Huijun Wang(5), Penny Gordon Larsen(3,4) ((1) Division of Geriatric Medicine and Center for Aging and Health, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; (2) Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; (3) Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; (4) National Institute for Nutrition and Health Chinese Center for Disease Control and Prevention, China)

Background: Aging biology results in changes in body composition that are associated with adverse outcomes. Evidence suggests that cognitive status may lead to different phenotypes of body composition in older age. Objectives: We sought to evaluate whether cognition in late mid-life is associated with different clusters of body composition phenotypes. Methods: We included participants aged 60+ in 2015 from the China Health and Nutrition Survey, a nationally representative survey, with complete bioelectrical impedance analysis, body composition, and anthropometry measures in 2015 and cognitive data collected 9 to 11 years prior to 2015. Cognition was estimated based on a subset of the modified Telephone Interview for Cognitive Status (TICS, 0–27). Latent class analysis was done to identify different body composition patterns. Our primary analysis identified classes based on percent body fat, total skeletal muscle/height2, and BMI adjusted for age and sex. In sensitivity analysis we ran the same models replacing appendicular mass for total skeletal muscle. We combined latent classes to improve study power and align with the Fried frailty phenotype (robust, pre-frail, frail). Results: Of the 1,424 adults (55% female, age 72.0±5.9 in 2015), mean BMI was 23.8±3.6, and TICS at the visit prior to 2015 was 13.5±6.2. Five classes were found to have the best fit: Class I (n=29, moderate BMI, lowest body fat, highest muscle); Class II: (n=211, lowest BMI, % body fat, and muscle); Class 3 (n=65, high BMI, body fat, muscle); Class 4 (n=602, low BMI, low body fat, low muscle); and Class 5 (n=517, moderate BMI, body fat, muscle). In our 5-class model, higher cognition roughly 10 years prior was associated with lower odds of being in Class 2 (low BMI, low % body fat, and low muscle mass) as compared to Class 5 (moderate BMI, body fat, muscle) with an odds ratio of 0.91 [0.82,1.00]). Presence of mild cognitive impairment or dementia in 2006 was suggestive of frailty at follow-up. Conclusion: Cognitive impairment reflected by the TICS may be a marker for future frailty phenotypes over time. Future, adequately powered studies are needed to confirm a statistically significant relationship.

OC15- CT-DERIVED BODY COMPOSITION IS ASSOCIATED WITH GRIP STRENGTH AND GAIT SPEED IN MROS STUDY. Peggy M. Cawthon(1), Katey Webber(1), Eric S. Orwoll(2), Kristine E. Ensrud(3) Jane A. Cauley(4), Leon Lenchik(5) ((1) California Pacific Medical Center, Research Institute, San Francisco, CA USA; (2) Oregon Health and Sciences University, Portland, OR, USA; (3) University of Minnesota, Minneapolis, MN, USA; (4) University of Pittsburgh, Pittsburgh, PA, USA; (5) Wake Forest University, Winston-Salem, NC, USA)

Background: Automated analysis of biomarkers of body composition on CT images may improve prediction of physical function decline in older adults. Objective: In 2,644 men (mean age 74.0) in MrOS, determine if body composition biomarkers derived from abdominal CT images are associated with grip strength and walking speed. Methods: On CT images at L3 level, our fully-automated machine learning algorithm determined total abdominal skeletal muscle area (SMA) — biomarker of sarcopenia, skeletal muscle density (SMD) — biomarker of intramuscular myosteatosis, intermuscular adipose tissue area (IMAT) — biomarker of intermuscular myosteatosis, visceral adipose tissue area (VAT), and subcutaneous adipose tissue area (SAT). Association of CT metrics with grip strength and walking speed was determined using linear regression models adjusted for CT parameters (scanner model, slice thickness, tube current) and participant age and height. Results: For grip strength, Muscle area, muscle density, VAT, and SAT (but not IMAT) were significantly associated with grip strength in fully adjusted models. [standardized βs per 1 SD increment for grip: SMA (β = 2.16, CI = 1.78, 2.55); SMD (β = 0.56, CI = 0.16, 0.97); VAT (β = −0.65, CI = −1.04, −0.26); SAT (β = −0.41, CI = −0.75, −0.06); IMAT (β = −0.02, CI = −0.66, 0.62] For gait speed, only IMAT and VAT were associated with gait speed in fully adjusted models. [standardized βs, 1 SD increment in IMAT (β = −0.04, CI = −0.06, −0.02) and VAT (β = −0.01, CI = −0.02, −0.00); other non-significant β not shown]. Conclusion: In older men, CT-derived biomarkers of sarcopenia, intramuscular myosteatosis, and adiposity, but not the biomarker of intermuscular myosteatosis, are associated with lower grip strength. CT-derived biomarker of intermuscular myosteatosis and VAT are associated with slower gait speed.

OC16- COMBINED PHYSICAL AND COGNITIVE STIMULATION IN AN INNOVATIVE DUAL-TASK IN MICE AND APPLICATION IN AGING. Elpidio Attoh-Mensah, Antoine Huret, Camille Laurent, Marianne Léger, Gilles Loggia, Daniel Zuba, Chantal Chavoix, Pascale Schumann-Bard, Thomas Fréret (Normandie Université, UNICAEN, INSERM, COMETE, CYCERON, CHU de Caen, Caen, France)

Background: Physical activity (PA) is a recommended non-pharmacological intervention to prevent age-related frailty (for review see Smith et al., 2010). PA interventions have been associated with functional improvement particularly, through enhancement of gait and cognitive performance in older adults. Recent studies argued that PA would convey a stronger impact when combined with cognitive challenges within a single dual-task (DT) (Lipardo et al.,2018). Having an animal model of dual-tasking would therefore be useful to better understand underlying mechanisms of these benefits. Objectives: In this study, we sought to develop an innovative model of dual-task — combining physical activity and cognitive challenge — in adult mice. The effects of DT practice on motor and cognitive performance in young mice and subsequent effects at an older age were also examined. Methods: C57BL/6J mice of 3 months of age were trained to visual discrimination task and then to its reversal, in touchscreen chambers. During cognitive training sessions, mice were randomly split into 3 groups (n=10/group), either without PA (control), or with PA administrated apart from (single task, ST) or simultaneously with (DT), the cognitive task. PA was given through a homemade treadmill, specifically designed to fit in the touchscreen chambers. The speed was set at 9 m/min. Besides, mice were retested 15 months later, i.e. at 19 months, to assess long-lasting effect of single and dual tasks (versus control) on aged mice performance. Results: First, we have shown that this dual-task model was feasible in mice. Besides, young mice in DT group displayed better procedural (p<0.001) and cognitive flexibility (p<0.01) performance, than either ST or control groups. Furthermore, these positive impacts still remained 15 months later in aged mice, that displayed both better cognitive (p<0,001) and motor (p<0,009) performance in the DT versus ST and control groups. Conclusion: We developed for the first time a dual stimulation task in mice. This innovative task could help to unravel physiological and neurobiological correlates of the benefits of dual-tasking on cognitive and motor performance in various normal and pathological conditions.

OC17- PLASMA INFLAMMATORY MARKERS PREDICT LONGITUDINAL TRAJECTORIES OF INTRINSIC CAPACITY IN OLDER ADULTS. Wan-Hsuan Lu(1,2), Bruno Vellas(1,2), Philipe de Souto Barreto(1,2) ((1) Gerontopole of Toulouse, Institute of Ageing, Toulouse University Hospital (CHU Toulouse), Toulouse, France; (2) Maintain Aging Research team, Centre d’Epidémiologie et de Recherche en santé des POPulations (CERPOP), Inserm, Université Paul Sabatier, Toulouse, France)

Background: Intrinsic capacity (IC), the composite of physical and mental capacities, declines with age at different rates and patterns between individuals. Whether aging biomarkers can predict different IC trajectories remains unclear. Objectives: This study had two objectives: (1) to identify IC multi-trajectories among older adults; (2) to investigate the association of trajectory groups with plasma biomarkers related to inflammation and mitochondrial dysfunction. Methods: This is a secondary analysis of the Multidomain Alzheimer Preventive Trial (MAPT). We included 1,271 community-dwelling older adults aged ≥70 with IC data over four years. IC was operationalized as a 0-to-100 score consisting of cognition (assessed by Mini-Mental State Examination [MMSE]), locomotion (evaluated by Short Physical Performance Battery [SPPB]), psychology (measured by Geriatric Depression Scale [GDS]), and vitality (assessed by handgrip strength). We performed group-based multi-trajectory modeling to identify participants who followed similar longitudinal patterns across four IC domains. Associations between the multi-trajectory groups and plasma biomarker levels were examined by multinomial logistic regression. Results: Five IC multi-trajectory groups were determined: low in all domains (8%), low locomotion (25%), low psychological domain (17%), robust (28%), and robust with high vitality (22%). The “low in all domains” group had the oldest age, the highest percentages of low educational levels, and the highest number of chronic diseases (all p<0.01). Compared to the best trajectory group (i.e., robust with high vitality), elevated levels of plasma interleukin-6 (IL-6), tumor necrosis factor receptor-1 (TNFR-1), and growth differentiation factor-15 (GDF-15) were associated with a higher risk of belonging to the “low in all domains” group (IL-6: relative risk ratio (RRR) [95% CI] = 1.42 [1.07 – 1.88]; TNFR-1: RRR = 1.46 [1.09 – 1.96]; GDF-15: RRR = 1.99 [1.45 – 2.73]). Higher GDF-15 was associated with an increased risk of being in the “low locomotion” group (RRR = 1.48 [1.17 – 1.89]) and “low psychological domain” group (RRR = 1.29 [1.01 – 1.64]). Conclusion: Plasma biomarkers reflecting inflammation distinguished older people with multi-impaired IC trajectories from those with high-stable IC trends.

OC18- THE PATHOGENESIS OF SARCOPENIA IS DIFFERENT IN THE GROUP OF MALE COPD AND NON-COPD SUBJECTS. Chih-Ming Lin(1), Jhih-Jhen Wu(2), Huan-Ting Lin(3), Shih-Wei Huang(4) ((1) Division of Internal Medicine, Taipei Chang Gung Memorial Hospital, Taipei, Taiwan; (2) Chang Gung Medical College, Taipei, Taiwan; (3) Mackey Medical College, Taipei, Taiwan; (4) Department of Internal Medicine, Linko Chang Gung Memo rial Hospital, Taipei, Taiwan)

Background: The incidence and prevalence of sarcopenia is strongly age, sex, and diseases dependent. Men are more likely to develop sarcopenia according to previous study. The purpose of this study was to identify possible pathogenesis of sarcopenia for the male older adults with and without chronic obstructive pulmonary disease (COPD) using plasma metabolites. Objective: Cross-section study. Methods: Our participants are a group of healthy older people who live in retirement homes and can take care of their daily lives without nursing assistance. There were 305 enrolled and the average age was 81.8 years old with 43.3% being male. The incidence of COPD was 12.5% according to the 2017 GOLD guidelines. There were 38 in group of COPD subjects and 267 in the group of non-COPD subjects. There were 20 had sarcopenia in 25 COPD of 132 male subjects and 5 had sarcopenia in 13 COPD of 173 female subjects according to Asian Working Group for Sarcopenia (AWGS) 2019 criteria. Mass spectrometry-based profiling of metabolites in plasma of all participants were measured and then the results were calculated the difference between the group of male COPD and non-COPD subjects with/without sarcopenia. Results: Metabolite patterns of male COPD and non-COPD subjects with/without sarcopenia were explored in our study. Plasma acylcarnitines (C2, C4, C5, C9 and C14) were identified with higher concentrations with significant difference in the group of male non-COPD subjects with sarcopenia. Plasma amino acid (BCAA, essential AA, Ile, Leu, Lys, Orn, Thr, and Val) were identified with lower concentrations with significant difference in the group of male non-COPD subjects with sarcopenia. The concentration of plasma acylcarnitines and amino acid in the group of male COPD subjects with sarcopenia did not have difference with significant difference compared with the group of male COPD subjects without sarcopenia. Conclusion: The pathogenesis of sarcopenia in the group of male COPD and non-COPD subjects may be different by the metabolomic study.

OC19- HEALTH-RELATED QUALITY OF LIFE IN SARCOPENIA: A SYSTEMATIC REVIEW AND METAANALYSIS. Charlotte Beaudart(1), Céline Demonceau(1), Jean-Yves Reginster(1), Médéa Locquet(1), Matteo Cesari(2,3), Alfonso J. Cruz Jentoft(4), Olivier Bruyère(1) ((1) WHO Collaborating Center for Public Health aspects of musculoskeletal health and ageing, Division of Public Health, Epidemiology and Health Economics, University of Liège, Belgium; (2) Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; (3) Geriatric Unit, IRCCS Istituti Clinici Scientifici Maugeri, Milan, Italy; (4) Servicio de Geriatría, Hospital Universitario Ramón y Cajal (IRYCIS). Madrid, Spain)

Background: The decrease of physical abilities and functional decline that can be caused by musculoskeletal disorders as sarcopenia, can lead to a higher level of dependence and disabilities. Therefore, it may influence patient reported outcome measures (PROM), such as the health-related quality of life (HRQoL). The purpose of this systematic review and meta-analysis is to provide an exhaustive view on the relationship between sarcopenia and HRQoL. Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were followed through the whole process of this work. A protocol was previously published on PROSPERO. The electronic databases MEDLINE, Scopus, Allied and Complementary Medicine (AMED), EMB Review — ACP Journal Club, EBM Review- Cochrane Central of Register of Controlled Trials and APA PsychInfo were searched up to October 2022 for observational studies reporting a HRQoL assessment in both sarcopenic and non-sarcopenic individuals. Study selection and data extraction were carried out by two independent researchers. Meta-analysis was performed with a random effect model giving an overall standardized mean difference (SMD) and its 95% confidence interval (CI) between sarcopenic and non-sarcopenic. Quality of individual studies was measured using the Newcastle Ottawa Scale and strength of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. Results: The search strategy identified 3,725 references from which 43 observational studies were eligible and included in this meta-synthesis study. A significant lower HRQoL was observed for sarcopenic individuals compared to non-sarcopenic (SMD −0.76; 95%CI −0.95; −0.57). Significant heterogeneity was associated with the model (I2=93%, Q test <0.01). Subgroups analysis showed that the specific questionnaire SarQoL discriminates better sarcopenia in regards of HRQoL (SMD −1.09; 95%CI −1.44; −0.74 versus −0.49; 95%CI −0.63; −0.36 with generic tools; p-value for interaction <0.01). A higher difference of HRQoL between sarcopenic and non-sarcopenic was found for individuals residing in living home cares compared to community-dwelling individuals (p-value for interaction <0.001). No differences between age, diagnostic techniques, and continents/regions were found. Level of evidence was rated as moderate using GRADE assessment. Conclusion: This systematic review and meta-analysis combining 43 observational studies demonstrates that HRQoL is significantly reduced in sarcopenic patients. Using disease-specific HRQoL instruments may better discriminate sarcopenic patients in regards of their quality of life.

OC21- FISH INTAKE AND PRE-FRAILTY IN NORWEGIAN OLDER ADULTS. A PROSPECTIVE COHORT STUDY: THE TROMSØ STUDY 1994–2016. Dina Moxness Konglevoll(1), Lene Frost Andersen(1), Laila Arnesdatter Hopstock(2), Bj0rn Heine Strand(3,4,5), Magne Thoresen(6), Torunn Holm Totland(5), Anette Hjartåker(1), Monica Hauger Carlsen(1) ((1) Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway; (2) Department of Health and Care Sciences, UiT The Arctic University of Norway, Troms0, Norway; (3) The Norwegian National Centre for Ageing and Health, Vestfold Hospital Trust, Tϕnsberg, Norway; (4) Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway; (5) Department of Physical Health and Ageing, Norwegian Institute of Public Health, Oslo, Norway; (6) Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway)

Background: Fish are suggested as being part of a healthy diet and a dietary factor in the prevention of frailty. However, the influence of a lifelong habitual fish intake on pre-frailty is unknown. Objective: To investigate the longitudinal association between the frequency of fish intake and pre-frailty in Norwegian older adults. Methods: This prospective cohort study used data from the fourth (1994–1995), sixth (2007–2008) and seventh (2015–2016) survey of the large, population-based Tromsø Study in Tromsø, Norway. We included 4350 men and women aged ≥65 years with data on frailty (modified Fried’s frailty phenotype: weight loss, exhaustion, and low physical activity, grip strength and walking speed) in Tromsø7 and self-reported frequency of fish intake (low (0–3 times/month), medium (1–3 times/week) and high (≥4 times/week)) in Tromsø4, Tromsø6 and Tromsø7, respectively. We used multivariable logistic regression to study the association between (1) frequency of intake of lean, fatty and total fish in Tromsø6 and pre-frailty in Tromsø7, and (2) stable patterns of total fish intake across Tromsø4, Tromsø6 and Tromsø7 (21 years) and pre-frailty in Tromsø7. Results: The prevalence of pre-frailty was 28% (n = 1124). A medium and high intake of fatty fish in Tromsø6 was associated with 18% (odds ratio (OR) = 0.82, 95% confidence interval (CI) = 0.69, 0.98) and 37% (OR = 0.63, 95% CI = 0.43, 0.91) lower odds of pre-frailty after 8 years, compared with a low intake. For lean and total fish, a high intake was associated with 28% (OR = 0.72, 95% CI = 0.53, 0.97) and 31% (OR = 0.69, 95% CI = 0.52, 0.91) lower odds of pre-frailty after 8 years, respectively, compared with a low intake. There was no association between patterns of total fish intake over 21 years and pre-frailty. Conclusion: A higher frequency of intake of lean, fatty and total fish was associated with lower odds of pre-frailty after 8 years in older community-dwelling Norwegian adults. This underlines the importance of promoting frequent fish intake as part of a healthy diet to facilitate healthy ageing.

OC23- DESCRIPTIVE STUDY OF THE ICOPE PATHWAY FROM STEP 1 TO 3 IN THE INSPIRE-T COHORT. Catherine Takeda(1), Christelle Cantet(1), Emeline Muller(1), Sophie Guyonnet(2), Bruno Vellas (1,2) for the INSPIRE Plateform group ((1) Gérontopôle, Geriatric Department, CHU of Toulouse, Toulouse, France; (2) CERPOP Inserm UMR 1295, Toulouse, France; University of Toulouse III, Toulouse, France)

Background: The World Health Organization (WHO) has been leading international action plans under the United Nations 2021–2030 Decade of Healthy Ageing. In 2017-2019 WHO published guidelines on the implementation of an Integrated Care for Older People (ICOPE) framework targeting intrinsic capacity through mobility, cognition, psychological, vitality, hearing and vision. The INSPIRE study is implementing this program in the INSPIRE-T cohort (1014 participants; aged 20–102 years at baseline; with 10 years follow-up). Objectives: The primary objective of this study was to describe the intrinsic capacity characteristics in the INSPIRE-T cohort and identify abnormalities in intrinsic capacity during step 1 with the screening tool, step 2 with a full assessment of each capacity and describe the different step 3 (care plan). Methods: In this prospective study, we analyzed the ICOPE step 1 to 3 for the participants aged 60 years and older from the INSPIRE-T cohort at base line. All individuals were screened using the step 1 screening tool. In-depth assessments (step 2) was systematically performed regarding the results of the screening test and a personalized care plan was proposed according to the ICOPE guidelines. Results: Between October 2019, and March 2022, 603 participants, 60 years and older, (mean age 747, SD 88 years; 357 [59.2%] of whom were women) were included in the INSPIRE-T cohort. 595 (988%) participants had a positive intrinsic capacity result during screening at baseline. Step 2 findings: mean MMSE 28.2, SD 2.2; mean MNA 27.4, SD 2.3; mean PHQ-9 3.3, SD 3.8; mean SPPB 11.2 SD 1.8 and 213 (36.2%) had visual impairment. Among the subjects 338 (56.5%) were robust, 206 (34.4%) we