Chronic Kidney Disease and the Exposome of Ageing.

Abstract

The gap between improvements in lifespan and age-related health is widening. Globally, the demographic of ageing is increasing and there has emerged a 'diseasome of ageing', typified by a range of non-communicable diseases which share a common underlying component of a dysregulated ageing process. Within this, chronic kidney disease is an emerging global epidemic.The extensive inter-individual variation displayed in how people age and how their diseasome manifests and progresses, has required a renewed focus on their life course exposures and the interplay between the environment and the (epi)genome. Termed the exposome, life course abiotic and biotic factors have a significant impact on renal health.We explore how the exposome of renal ageing can predispose and affect CKD progression. We discuss how the kidney can be used as a model to understand the impact of the exposome in health and chronic kidney disease and how this might be manipulated to improve health span.Notably, we discuss the manipulation of the foodome to mitigate acceleration of ageing processes by phosphate and to explore use of emerging senotherapies. A range of senotherapies, for removing senescent cells, diminishing inflammatory burden and either directly targeting Nrf2, or manipulating it indirectly via modification of the microbiome are discussed.