Zhang, Bruce; (2025) Understanding ageing through biogerodemography. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The biological process of ageing (senescence) affects all life forms, with inescapable effects upon health and survival. However, its cause, course and consequences are far from understood, despite increasing scientific and commercial efforts in recent decades. A cornerstone of ageing research is the study of lifespan – the timing of that transition from life to death. Classical demographic studies of lifespan attempt to understand the biological ageing process through these mortality patterns. Most notably, the Gompertz model of mortality mathematically captures the exponential rise in mortality rates in diverse animal populations, including humans. The two parameters of this model have been widely used to infer biological properties of these populations; for instance, it is commonly thought that the scale parameter reflects the level of ageing-independent mortality, whereas the rate parameter reflects the rate of ageing. However, an empirical foundation for these views has not yet emerged, despite continued application of such mortality models in ageing research. In this thesis, I use the nematode Caenorhabditis elegans to develop a “biogerodemographic” approach to understanding ageing, which couples the collection and analysis of biological data to the traditional demographic analysis of lifespan. This enables explanation of population-level mortality features (e.g. Gompertz parameters) in terms of individual-level biological processes. I find in C. elegans an unexpected inversion of traditional views: the Gompertz scale parameter better reflects ageing rate than ageing-independent mortality, whereas the Gompertz rate parameter better reflects inter-individual variation in the ageing process than ageing rate itself. Remarkably, these new biological interpretations also provide a parsimonious explanation for the enigmatic, inverse Strehler-Mildvan correlation between the Gompertz parameters. Finally, I demonstrate the broader utility of the biogerodemographic approach, in making sense of the individual- and age-specific role of insulin/IGF-1 signalling in C. elegans ageing. The intention of this thesis is therefore to provide a methodological roadmap between demographic and biological ageing, whose combined study has been and will continue to be an unavoidable and important challenge on the path to understanding the biology of ageing.

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