The role of epigenetics in renal ageing

Paul G. Shiels*, Dagmara McGuinness, Maria Eriksson, Jeroen P. Kooman, Peter Stenvinkel

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

62 Citations (Web of Science)

Abstract

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.

Original languageEnglish
Pages (from-to)471-482
Number of pages12
JournalNature Reviews Nephrology
Volume13
Issue number8
DOIs
Publication statusPublished - Aug 2017

Keywords

  • CHRONIC KIDNEY-DISEASE
  • HUTCHINSON-GILFORD-PROGERIA
  • DNA METHYLATION AGE
  • CORONARY-HEART-DISEASE
  • LONG NONCODING RNAS
  • ALL-CAUSE MORTALITY
  • LIFE-STYLE FACTORS
  • CARDIOVASCULAR-DISEASE
  • CELLULAR SENESCENCE
  • GENE-EXPRESSION

Cite this