Department of Computer Science, University College London, Engineering Building, Malet Place, London, WC1E 7JG, UK.
Institute of Structural and Molecular Biology, University College London and Birkbeck, London, WC1E 6BT, UK.
Nat Commun. 2020 Feb 25;11(1):1043. doi: 10.1038/s41467-020-14785-0.
Genetic and environmental factors are key drivers regulating organismal lifespan but how these impact healthspan is less well understood. Techniques capturing biomechanical properties of tissues on a nano-scale level are providing new insights into disease mechanisms. Here, we apply Atomic Force Microscopy (AFM) to quantitatively measure the change in biomechanical properties associated with ageing Caenorhabditis elegans in addition to capturing high-resolution topographical images of cuticle senescence. We show that distinct dietary restriction regimes and genetic pathways that increase lifespan lead to radically different healthspan outcomes. Hence, our data support the view that prolonged lifespan does not always coincide with extended healthspan. Importantly, we identify the insulin signalling pathway in C. elegans and interventions altering bacterial physiology as increasing both lifespan and healthspan. Overall, AFM provides a highly sensitive technique to measure organismal biomechanical fitness and delivers an approach to screen for health-improving conditions, an essential step towards healthy ageing.
遗传和环境因素是调节生物寿命的关键因素，但这些因素如何影响健康寿命还不太清楚。能够在纳米尺度上捕捉组织生物力学特性的技术为研究疾病机制提供了新的视角。在这里，我们应用原子力显微镜（AFM）定量测量与衰老秀丽隐杆线虫相关的生物力学特性变化，同时捕获表皮衰老的高分辨率形貌图像。我们发现，不同的饮食限制方案和延长寿命的遗传途径会导致截然不同的健康寿命结果。因此，我们的数据支持这样一种观点，即延长寿命并不总是与延长健康寿命相一致。重要的是，我们确定了秀丽隐杆线虫中的胰岛素信号通路和改变细菌生理学的干预措施可以同时延长寿命和健康寿命。总的来说，AFM 提供了一种高度敏感的测量生物体生物力学适应性的技术，并提供了一种筛选改善健康状况的方法，这是迈向健康老龄化的重要一步。
