Welch Carly, Acharjee Animesh, Birch Rebecca, de Magalhães João Pedro, Duggal Niharika A, Hainsworth Alison, Hombrebueno Jose R, Jones Simon W, Lewis Jonathan, Mazaheri Ali, McGettrick Helen M, Nicholson Thomas, Partridge Judith, Pinkney Thomas, Steves Claire J, Tomkova Kristina, Wilson Daisy, Jackson Thomas A
Department of Twin Research & Genetic Epidemiology, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King's College London, 3rd Floor South Wing D Block, St Thomas' Campus, Westminster Bridge, London, SE17EH, UK.
Department of Ageing and Health, St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust, 9th Floor, Westminster Bridge, London, SE17EH, UK.
BMC Geriatr. 2025 Jul 8;25(1):502. doi: 10.1186/s12877-025-06109-y.
Ageing is a heterogeneous process, which is associated with heterogeneous resilience in older people. Cancer surgery and treatment may be associated with accelerated ageing in some older people; studying this process will improve understanding to enable treatments to prevent adverse effects on physical and cognitive function.
This study will recruit 172 participants aged 65 years and older scheduled to undergo elective colorectal surgery for cancer from two hospital sites (Guy's and St Thomas' NHS Foundation Trust and University Hospitals Birmingham NHS Foundation Trust). Assessments will be performed preoperatively, days 1-3 postoperatively, 30 days postoperatively, and 90 days postoperatively. These will include in-depth clinical phenotyping including handgrip strength, Short Physical Performance Battery, muscle ultrasound, cognitive tests, Electroencephalography, questionnaires including quality of life, and physical activity using remote devices. Serial blood and stool specimens will be collected across timepoints to measure underlying hallmarks of ageing including inflammation, dysbiosis, macroautophagy, cellular senescence, epigenetic alterations, mitochondrial dysfunction, and stem cell exhaustion. A machine learning approach will be utilised to evaluate the associations between trajectories in clinical and physiological parameters and fundamental biological processes.
This study represents an exciting collaboration between clinicians, fundamental scientists, and experts in machine learning. It offers the opportunity to characterise and understand complex pathways to enable future clinical trials directed towards the prevention of accelerated ageing through a stratified medicine approach.
衰老过程具有异质性，这与老年人的异质性恢复力相关。癌症手术和治疗可能会使一些老年人加速衰老；对这一过程进行研究将增进理解，从而使治疗能够预防对身体和认知功能的不良影响。
本研究将招募172名65岁及以上计划在两个医院地点（盖伊和圣托马斯国民保健服务信托基金以及伯明翰大学医院国民保健服务信托基金）接受择期结直肠癌手术的参与者。评估将在术前、术后第1至3天、术后30天和术后90天进行。这些评估将包括深入的临床表型分析，包括握力、简短体能状况量表、肌肉超声、认知测试、脑电图、包括生活质量的问卷以及使用远程设备进行的身体活动。将在各个时间点收集系列血液和粪便样本，以测量衰老的潜在特征，包括炎症、生态失调、巨自噬、细胞衰老、表观遗传改变、线粒体功能障碍和干细胞耗竭。将采用机器学习方法来评估临床和生理参数轨迹与基本生物学过程之间的关联。
本研究是临床医生、基础科学家和机器学习专家之间令人兴奋的合作。它提供了一个机会来表征和理解复杂的途径，以便未来能够通过分层医学方法开展旨在预防加速衰老的临床试验。
