13th International Conference on Frailty & Sarcopenia Research (ICFSR)

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TL;DR

This conference report summarizes the 13th International Conference on Frailty & Sarcopenia Research (ICFSR), covering symposia and oral communications on the biology, assessment, and clinical management of frailty and sarcopenia. Key findings include that biomarkers of cellular senescence (e.g., GDF-15, IL-6) predict mobility disability, mortality, and other adverse outcomes in older adults, and that interventions such as physical activity, caloric restriction, and the apelin receptor agonist BGE-105 may modify these biomarkers or attenuate muscle atrophy. The clinical significance lies in advancing the translation of geroscience into targeted interventions and improved risk stratification for frail and sarcopenic older adults.

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**Background:** The 13th International Conference on Frailty & Sarcopenia Research (ICFSR) brought together researchers to present the latest findings on the biological underpinnings, assessment methods, and clinical interventions for frailty and sarcopenia. The conference highlighted the geroscience hypothesis, which posits that fundamental aging processes—such as cellular senescence, mitochondrial dysfunction, and chronic inflammation—drive the development of these geriatric syndromes. A major theme was the need to translate biological discoveries into clinical practice and public health strategies.

**Methods:** The conference featured multiple symposia and oral communications presenting data from large cohort studies (e.g., LIFE, CALERIE, Health ABC, SOMMA, UK Biobank, SNAC-K), randomized controlled trials (e.g., DO-HEALTH, Vivifrail, PROMOTe, CRC-NORDIET), and preclinical models. Researchers employed a range of methodologies, including biomarker measurement (e.g., SASP proteins, miRNAs, metabolomics), advanced imaging (CT radiomics, MRI, DXA, BIA), and functional assessments (grip strength, gait speed, SPPB, 400-meter walk). Statistical approaches included Cox regression, linear mixed models, latent class analysis, and group-based trajectory modeling.

**Key Results:** - **Cellular Senescence Biomarkers:** In the LIFE study (n=1,377), multiple SASP proteins were associated with the onset of mobility disability. While no difference in SASP proteins was found between physical activity and healthy aging intervention groups, higher quartiles of accelerometry-measured moderate-intensity physical activity were associated with significantly lower concentrations of 10 SASP proteins (e.g., IL-6, TNF-a, MMP7). In the CALERIE trial, a two-year caloric restriction intervention significantly reduced circulating levels of several senescence biomarkers compared to an ad libitum diet. In the Health ABC study (n=1,681), high serum levels of GDF-15 (HR 1.9–2.6 for Q4 vs Q1), TNFR1 (HR 1.6–2.7), IL-6 (HR 1.8–2.3), MMP7 (HR 1.4–2.0), and activin A (HR 1.3–1.9) were associated with elevated risk for mortality, dementia, heart failure, mobility limitation, and hip fracture. - **Muscle Mitochondrial Energetics:** In the SOMMA cohort (n=873), maximal oxidative phosphorylation (OXPHOS) in muscle fibers was significantly associated with frailty status (p<0.001), with adjusted mean OXPHOS of 62.7 pmol/s*mg in robust, 58.2 in pre-frail, and 54.3 in frail participants. ATPmax measured by 31P MRS was not significantly associated with frailty after full adjustment (p=0.22). - **Interventions:** The apelin receptor agonist BGE-105 significantly improved multiple metrics of muscle atrophy in healthy older adults (≥65 years) on 10-day bed rest, including thigh circumference (placebo: −6.4% vs BGE-105: +0.8%; p<0.001) and vastus lateralis diameter (placebo: −21.2% vs BGE-105: −5.7%; p<0.01). L-citrulline supplementation combined with low-intensity resistance training in postmenopausal women with hypertension increased leg lean mass (0.5±0.2 kg vs 0.1±0.1 kg; p=0.046) and leg curl strength (6.9±0.9 kg vs 3.3±0.9 kg; p=0.04) compared to placebo plus training. The Vivifrail multicomponent exercise program over 12 weeks significantly improved intrinsic capacity composite score (β=0.48; 95% CI 0.24–0.74; p<0.001) in frail, cognitively impaired older adults. - **Epidemiology:** In the Swedish SNAC-K study (n=2,941), later birth cohorts showed an expansion of frailty, with a greater proportion of life spent frail despite increased life expectancy. In the UK Biobank (n=15,594 frail adults), a healthy lifestyle was associated with a 34% lower hazard of all-cause mortality (p<0.01).

**Clinical Implications:** The findings reinforce the central role of cellular senescence and mitochondrial dysfunction in frailty and sarcopenia. The identification of robust biomarkers like GDF-15 and IL-6 offers potential for risk stratification and monitoring intervention efficacy. The positive results from trials of BGE-105, L-citrulline, and multicomponent exercise programs provide promising avenues for pharmacological and lifestyle interventions. The expansion of frailty in later-born cohorts underscores the urgent need for effective public health strategies to compress morbidity and promote healthy aging.