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Journal Article
The role of epigenetics in renal ageing
2017
Overview
Key Points
The incidence of deaths owing to renal dysfunction is increasing globally in parallel with the ageing population
The epigenetic landscape of ageing is mediated by dynamic changes in the methylome and in chromatin structure, along with coordinated regulation of a complex range of molecular processes by noncoding RNAs in response to environmental changes
A mechanistic link is emerging between the epigenetic landscape of ageing and renal dysfunction based on regulation of ageing processes that are common across taxa
Epigenetic regulation of biological ageing in the kidney is influenced directly by nutrition, inflammation, the gut microbiome, psychosocial factors and lifestyle factors
Models of progeria provide important hypothesis-generating insights for future therapies designed to modify the epigenetic landscape in ageing and disease
Epigenetic interventions could potentially improve renal health, but caution is warranted given the potential for intergenerational and transgenerational effects
Epigenetic factors control gene expression and activity in response to environmental perturbation and regulate ageing processes throughout the life course. Here, the authors discuss the epigenetic regulation of signalling pathways that modulate ageing and their impact on the kidney.
An ability to separate natural ageing processes from processes specific to morbidities is required to understand the heterogeneity of age-related organ dysfunction. Mechanistic insight into how epigenetic factors regulate ageing throughout the life course, linked to a decline in renal function with ageing, is already proving to be of value in the analyses of clinical and epidemiological cohorts. Noncoding RNAs provide epigenetic regulatory circuits within the kidney, which reciprocally interact with DNA methylation processes, histone modification and chromatin. These interactions have been demonstrated to reflect the biological age and function of renal allografts. Epigenetic factors control gene expression and activity in response to environmental perturbations. They also have roles in highly conserved signalling pathways that modulate ageing, including the mTOR and insulin/insulin-like growth factor signalling pathways, and regulation of sirtuin activity. Nutrition, the gut microbiota, inflammation and environmental factors, including psychosocial and lifestyle stresses, provide potential mechanistic links between the epigenetic landscape of ageing and renal dysfunction. Approaches to modify the renal epigenome via nutritional intervention, targeting the methylome or targeting chromatin seem eminently feasible, although caution is merited owing to the potential for intergenerational and transgenerational effects.
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