Global Sessions

Immuno-Gerotherapeutics Targeting Senescent Cells for Age-associated Disease Tohru Minamino Juntendo University Graduate School of Medicine, Tokyo, Japan Genomic damage induced by oxidative stress associated with aging promotes the accumulation of senescent cells in tissues. Senescent cells are thought to be eliminated by activating the immune system through the secretion of inflammatory senescence-associated secretory phenotype (SASP) factors. However, because the system for removing senescent cells is impaired under pathological conditions (seno-anergy), their accumulation persists, and the chronic inflammation induced by SASP factors is believed to drive the progression of pathological aging.[1-3] We have investigated the role of senescent cells accumulated in tissues as a mechanism promoting pathological aging, and have provided evidence suggesting their involvement.[4-12] It has been suggested that senolysis using anti-apoptotic molecule inhibitors can improve pathological aging phenotypes, although this treatment approach faces many issues, including off-target effects. In contrast, we have been focusing on the regulation of immune responses against senescent cells—specifically targeting seno-antigens that are uniquely expressed in highly malignant senescent cells. We have succeeded in developing senolytic vaccine targeting the seno-antigen SAGP and demonstrated that administration of this vaccine improves pathological aging phenotypes in age-related diseases. We have also elucidated the molecular mechanisms of seno-anergy and have successfully developed senolytics that ameliorate seno-anergy and efficiently eliminate senescent cells. References 1. Ogrodnik M, Carlos Acosta J, Adams PD, d’Adda di Fagagna F, Baker DJ, Bishop CL, et al. Guidelines for minimal information on cellular senescence experimentation in vivo. Cell 2024;187:4150-75. 2. Shimizu I, Yoshida Y, Suda M, Minamino T. DNA damage response and metabolic disease. Cell Metab 2014;20:967-77. 3. Minamino T, Komuro I. Vascular aging: Insights from studies on cellular senescence, stem cell aging, and progeroid syndromes. Nat Rev Cardiol 2008;5:637-48. 4. Katsuumi G, Shimizu I, Suda M, Yoshida Y, Furihata T, Joki Y, et al. SGLT2 inhibition eliminates senescent cells and alleviates pathological aging. Nat Aging. 2024;4:926-38. 5. Suda M, Minamino T, Katsuumi G, Yoshida Y, Hayashi Y, Ikegami R, et al. Senolytic vaccination improves pathological aging. Nat Aging 2021;1:1117-26. 6. Yokoyama M, Okada S, Nakagomi A, Moriya J, Shimizu I, Nojima A, et al. Inhibition of endothelial p53 improves metabolic abnormalities related to dietary obesity. Cell Rep 2014;7:1691-703. 7. Shimizu I, Yoshida Y, Moriya J, Nojima A, Uemura A, Kobayashi Y, et al. Semaphorin3E-induced inflammation contributes to insulin resistance in dietary obesity. Cell Metab 2013;18:491-504. 8. Naito AT, Sumida T, Nomura S, Liu ML, Higo T, Nakagawa A, et al. Complement C1q activates canonical Wnt signaling and promotes aging-related phenotypes. Cell 2012;149:1298-313. 9. Shimizu I, Yoshida Y, Katsuno T, Tateno K, Okada S, Moriya J, et al. p53-induced adipose tissue inflammation is critically involved in the development of insulin resistance in heart failure. Cell Metab 2012;15:51-64. 10. Minamino T, Orimo M, Shimizu I, Kunieda T, Yokoyama M, Ito T, et al. A crucial role for adipose tissue p53 in the regulation of insulin resistance. Nat Med 2009;15:1082-7. 11. Sano M, Minamino T, Toko H, Miyauchi H, Orimo M, Qin Y, et al. p53-induced inhibition of Hif-1 causes cardiac dysfunction during pressure overload. Nature 2007;446:444-8. 12. Minamino T, Miyauchi H, Yoshida T, Ishida Y, Yoshida H, Komuro I. Endothelial cell senescence in human atherosclerosis: Role of telomere in endothelial dysfunction. Circulation 2002;105:1541-4. Failure to Thrive in Older Adults Shehan Silva1,2,3 1University Medical Unit, Colombo South Teaching Hospital, 2Department of Medicine, Faculty of Medical Sciences, University of Sri Jayewardenepura, 3Sri Lankan Association of Geriatric Medicine, Colombo, Sri Lanka Failure to thrive (FTT) in older adults is an increasingly recognized geriatric syndrome that differs substantially from its paediatric counterpart. Rather than failure to achieve developmental milestones, FTT in late life is defined by a progressive decline in physical, nutritional, and neuropsychiatric function, often representing the cumulative impact of frailty, multimorbidity, and social vulnerability. It is strongly associated with malnutrition, anorexia of ageing, depression, cognitive impairment, and medication-related adverse effects, all of which contribute to functional dependency, institutionalization, and increased mortality. The presentation highlights the epidemiology, clinical features, and consequences of FTT, drawing attention to its overlap with frailty and its role as a terminal pathway for many older adults. Special emphasis is placed on the biological mechanisms of anorexia of ageing, the influence of chronic inflammation, and the contribution of polypharmacy. A comprehensive geriatric assessment remains the cornerstone of diagnosis, enabling identification of potentially reversible factors across medical, psychological, and social domains. Management strategies include nutritional support, physical rehabilitation, psychological interventions, and environmental adaptations, alongside cautious use of pharmacological agents. Importantly, recognition of FTT should not be seen as a diagnosis of exclusion or as a label of futility, but as a clinical alarm that prompts detailed evaluation and individualized, person-centred care. Addressing FTT provides an opportunity to optimize function, reduce complications, and improve quality of life in older adult. Setting Up an Orthogeriatric Unit in Secondary/Tertiary Care Hospital Sunita Paul Middlemore Hospital, Auckland, New Zealand The orthogeriatric unit at Middlemore Hospital was started in 2000. MMH is a tertiary hospital in south Auckland serving over 500, 000 population with orthopaedic services providing acute care, trauma surgery including hip fractures ,tertiary centre for spinal surgery as well elective surgery, joint replacement etc. The principles guiding the establishment of the unit were as per the ANZ guideline for orthogeriatric model of care including Regular orthogeriatrician assessment, Rapid optimisation of fitness for surgery, Early identification of individual goals for multidisciplinary rehabilitation to recover mobility and independence and to facilitate return to prefracture residence and long-term wellbeing, Early identification of most appropriate service to deliver rehabilitation and Continued, coordinated and multidisciplinary review and discharge planning, liaison or integration with related services, including falls prevention, secondary fracture prevention, mental health, cultural services, primary care, community support services and carer support services. Over the last 25 years the ANZHFR was piloted at our service in 2014 and subsequently established and more recently ANZFFR established in 2022.Our unit has been a finalist for the ANZHFR gold hip award every year since it started in 2021. The two registries can be used to guide establishing good clinical practice when starting a new unit. The underpinning strategy was close collaboration between clinical and managerial leadership of departments of orthopaedics, anaesthesia and older people’s health, which has been ongoing and is crucial in its success. Life-space Mobility Assessment: From Reliability to Clinical Outcomes Cynthia Brwone Department of Medicine, LSUHSC School of Medicine, New Orleans, LA, USA This talk will provide an overview of life-space mobility (LSM), a crucial measure of real-world mobility in older adults. LSM quantifies movement from one’s home to the community, considering frequency and independence. The session will review the strong reliability and validity of established assessment tools, such as the University of Alabama at Birmingham Life-Space Assessment (LSA), highlighting its utility in both clinical practice and research. The second half of the talk will present compelling evidence linking restricted LSM to significant health outcomes, including increased risk of hospitalization, cognitive decline, falls, poor quality of life, and mortality. Attendees will gain insight into how LSM can serve as an important indicator for risk assessment and intervention targeting in aging populations. Connecting Science, Practice, and Education in Long-term Care: The Dutch Living Lab Experience Irma Everink Living Lab in Ageing and Long-term Care, Maastricht University, Maastricht, The Netherlands The Living Lab in Ageing and Long-Term Care is a collaborative initiative where academia and long-term care (LTC) providers join forces to enhance the quality of life and care for older adults in LTC, as well as the quality of work for staff. This partnership encompasses academics, LTC staff, residents, and relatives working together to conduct research and apply research findings in practice. The model originated in Maastricht, Netherlands, and is now being replicated globally. A pivotal element of the Living Lab model is the Scientific Linking Pin (LP): a senior researcher who dedicates one day per week to work for one of the LTC organizations within the network. The LP role is viewed as a critical one, influencing the model’s success. This talk will elaborate on the organization, business model and benefits of the living lab, and share experiences of the linking pin role.