Parasitic infection and resource acquisition shape senescence through oxidative stress and energy depletion.

There is currently no theory which mechanistically links parasite virulence and host senescence. One driver of senescence is energy metabolism. We expect parasites to contribute to senescence because infection increases energy allocation to the immune system, which elevates oxidative stress and damages macromolecules. Additionally, parasites deplete their host's energy, which can increase the host's rate of mortality. While these within-host processes can contribute to mortality, they also determine the risk of parasite infection through epidemiological dynamics. To understand quantitatively the impact of these interactions on infection dynamics and on the evolution of within-host parasite growth (virulence), we developed a multiscale model that describes within-host and among-host dynamics. We found that infection prevalence is maximized at intermediate levels of resource acquisition only when energy depletion contributes to senescence. Furthermore, for a single resource level, there are 2 evolutionary equilibria for the parasite growth rate. This is the first time the molecular mechanisms determining senescence have been considered in the context of parasite infection, allowing us to link virulence and senescence. Our mechanistic framework provides an alternative to the virulence-transmission trade-off and reconciles conflicting empirical findings on the impact of resources on epidemiological dynamics and virulence.