title: Age-associated molecular changes in the kidney in aged mice.
abstract: BACKGROUND
  Aging is a multifactorial process characterized by a progressive decline in physiological function. Decreased kidney function is associated with cardiovascular disease and mortality. Therefore, increasing our insight into kidney aging by understanding the anatomic, physiologic, and pathologic changes of aging in the kidney is important to prevent disastrous outcomes in elderly people.
  
  
  METHODS
  Male two-, 12-, and 24-month-old C57/BL6 mice were used in this study. We measured histological change, oxidative stress, and aging-related protein expression in the kidneys.
  
  
  RESULTS
  Twenty-four-month-old mice displayed increased albuminuria. Creatinine clearance decreased with aging, although this was not statistically significant. There were increases in mesangial volume and tubulointerstitial fibrosis in 24-month-old mice. There were also increases in F4/80 expression and in apoptosis detected by TUNEL assay. Urine isoprostane excretion increased with aging and SOD1 and SOD2 were decreased in 24-month-old mice. Oxidative stress may be mediated by a decrease in Sirt1, PGC-1α, ERR-1α, and PPARα expression. Klotho expression also decreased.
  
  
  CONCLUSIONS
  Our results demonstrate that Sirt1 was decreased with aging and may relate to changed target molecules including PGC-1α/ERR-1α signaling and PPARα. Klotho can also induce oxidative stress. Pharmacologically targeting these signaling molecules may reduce the pathologic changes of aging in the kidney.
authors: Division of Nephrology, Department of Internal Medicine, College of Medicine, Catholic University of Korea, Seoul 137-040, Republic of Korea.
authors: Ji Hee
authors: JH
authors: Lim
authors: Eun Nim
authors: EN
authors: Kim
authors: Min Young
authors: MY
authors: Kim
authors: Sungjin
authors: S
authors: Chung
authors: Seok Joon
authors: SJ
authors: Shin
authors: Hyung Wook
authors: HW
authors: Kim
authors: Chul Woo
authors: CW
authors: Yang
authors: Yong-Soo
authors: YS
authors: Kim
authors: Yoon Sik
authors: YS
authors: Chang
authors: Cheol Whee
authors: CW
authors: Park
authors: Bum Soon
authors: BS
authors: Choi
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis; D003404:Creatinine / Q000378:metabolism; D005355:Fibrosis; D005786:Gene Expression Regulation; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058990:Molecular Targeted Therapy; D018384:Oxidative Stress; D047493:PPAR alpha / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011960:Receptors, Estrogen / Q000378:metabolism; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D000097983:ERRalpha Estrogen-Related Receptor; D000099156:Superoxide Dismutase 2
chemical_list: D000943:Antigens, Differentiation; D003404:Creatinine; D047493:PPAR alpha; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011960:Receptors, Estrogen; D056564:Sirtuin 1; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D015534:Trans-Activators; D014157:Transcription Factors; D000097983:ERRalpha Estrogen-Related Receptor; D000099156:Superoxide Dismutase 2; C485290:Ppargc1a protein, mouse; C036763:monocyte-macrophage differentiation antigen; C000606291:Sod1 protein, mouse; C470545:Sirt1 protein, mouse