title: Molecular events in kidney ageing.
abstract: OBJECTIVE
  Ageing of the kidney is a problem of clinical and basic interest. The problem of renal dysfunction and end-stage renal disease is a major burden on the health system, and old donor age is a major limitation on the use of donor organs and on survival of transplanted kidneys. Moreover, stresses linked to nephropathies, postoperative stress, inflammation and allograft rejection can lead to premature senescence of renal cells thus accelerating organ atrophy. Age-related and disease or stress-related nephron loss could reflect both the limited ability of epithelial cells to repair and replicate in the face of environmental stresses, and limitations on the number of cell replications caused by telomere shortening. Therefore, elucidating cellular senescence mechanisms is relevant to kidney diseases and kidney transplantation.
  
  
  RESULTS
  Recent findings suggest additive effects of replicative and environmental stress-induced senescence in cellular and organ ageing. In particular, ATM/p53/p21 and Ras/p38/p16 pathways have been shown to co-contribute to the overall cellular senescence, which is caused by extrinsic and intrinsic stimuli. Moreover, the role of epigenetic factors, including protein acylation/deacetylation, chromatin remodeling or caloric restriction, is the focus of recent studies on ageing and senescence.
  
  
  CONCLUSIONS
  Despite significant progress, cellular senescence is still better understood in vitro than in vivo. So far, p16 remains the best marker of chronological age in the kidney, and can be considered as an indicator of premature senescence caused by stresses or disease. The beneficial effects of caloric restriction on organ ageing and the role of histone acetylation in pathologic states in rodents are of considerable interest, and deserve future studies.
authors.affiliation: Department of Medicine, Division of Nephrology and Transplantation Immunology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Konrad S
authors.initials: KS
authors.lastname: Famulski
authors.forename: Phillip F
authors.initials: PF
authors.lastname: Halloran
mesh_terms: D000375:Aging / Q000235:genetics* / Q000502:physiology; D000818:Animals; D015415:Biomarkers; D031204:Caloric Restriction; D019942:Genes, p16 / Q000502:physiology; D006085:Graft Survival / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000502:physiology*; D016030:Kidney Transplantation / Q000009:adverse effects; D023421:Models, Animal; D019737:Transplants
chemical_list: D015415:Biomarkers