Ignoring the planet: A critical blind spot for research on ageing.

Although research on ageing has largely concentrated on understanding the fundamental biology of the ageing process and devising pharmaceutical interventions in order to slow it down, increasing evidence has underscored the crucial role of environmental inputs across the life course and across generations, in shaping both individual and intergenerational trajectories of age-related health. These include nutrition, air pollution, social deprivation, lifestyle factors, climate change and exposure to environmental toxins, including microplastics and nanoplastics. The development of the concept of the exposome of ageing and the emergence of the new field of 'exposomics' have identified a blind spot, in particular, for geroscience. The impact of the exposome affecting human 'healthspan' (i.e., years lived in good health), extending across generations, is significant and yet under-explored in research. As such, it is under-appreciated that the declining health of the planet will have intergenerational ripple effects, epigenetically priming adverse health in future generations. We discuss the capacity to manipulate our exposome to mitigate against such effects, by addressing root causes, rather than symptoms, of both physiological and planetary dysregulation, dysfunction and decay. We propose a systems-based framework that reconnects research on ageing with exposomics and planetary ecology, creating a new field of 'ecological or exposome pharmacology', harnessing the activity of Nrf2 as a senotherapeutic intervention to improve trans- and intergenerational physiology in the face of declining planetary health.