Abstract
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.
Highlights
Genetic and environmental factors are key drivers regulating organismal lifespan but how these impact healthspan is less well understood
Atomic Force Microscopy (AFM) is a type of scanning probe microscope with a resolution in the order of a few nanometres, which utilises the fine probe to: (1) detect changes in the mechanical properties of a sample through force-indentation measurements (Fig. 1a, Supplementary Fig. 1a, Supplementary Data 1), which can be used to calculate the stiffness or Young’s Modulus (YM) using the Hertz model for contact mechanics (Supplementary Fig. 1b); and (2) perform high-resolution imaging of the surface of a sample, which can be illustrated by three-dimensional topographic images
We found that growing worms on B. subtilis increased lifespan (19.81%, log rank p < 0.001, Fig. 5a, Supplementary Data 2), whereas worms fed on C. aquatica were short-lived when compared with worms fed on E. coli OP50 (−7.47%, log rank p < 0.001, Fig. 5a, Supplementary Data 2), as previously reported[54,55,56]
Summary
Genetic and environmental factors are key drivers regulating organismal lifespan but how these impact healthspan is less well understood. Despite similarities in health-related decay between evolutionarily distant organisms, the adoption of a frailty index in worms and other model organisms is rarely implemented[4,10] This is because currently used health biomarker measurements remain loosely defined in the context of the ageing process and are prone to human or biological bias, suggesting the need for additional health biomarkers for the assessment of organismal healthspan with age. Cells are under constant mechanical pressure from shear stress and contractile stress from their own acto-myosin cytoskeleton and from neighbouring cells, through confinement in space, gravity or hydrostatic pressure These factors have been shown to influence key molecular processes such as ion channel activity, gene regulation and protein expression[14,15]. This work paves the way for the future dissection of the molecular pathways underlying healthspan, and potentially tilts the balance in the paradigm of healthspan gains versus lifespan extension
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
