title: Accelerated senescence in kidneys of low-birth-weight rats after catch-up growth.
abstract: Epidemiological studies show a strong association between low birth weight and hypertension, renal, and cardiovascular disease, especially after catch-up growth. Senescence is an important contributor to the progression of chronic disease. Developmentally programmed premature senescence may be a link among low birth weight, catch-up growth, and adult disease. Low birth weight was induced by feeding pregnant rats a low-protein diet from day 12 of gestation to 10 days postdelivery. Low- and normal-birth-weight male offspring were weaned onto regular or high-calorie diets to enhance catch-up growth. Kidneys and hearts of offspring were analyzed for RNA and protein markers of stress-induced senescence (p16, p21, p53, Rb). Markers of mitochondrial stress (p66Shc) and activation of endoplasmic reticulum protein secretion (Ero1alpha) were analyzed as regulators of reactive oxygen species generation. Reactive oxygen species are known to be associated with premature aging. Senescence markers were not different in low- or normal-birth-weight kidneys at birth. During rapid catch-up growth, p16 and p21 increased significantly in low-birth-weight kidneys and hearts (P < 0.01). Renal p16 levels increased progressively and were significantly higher in low-birth-weight kidneys at 3 and 6 mo (P < or = 0.02). Renal p66Shc and Ero1alpha were significantly higher in low- compared with normal- birth-weight kidneys at 6 mo, suggesting reactive oxygen species generation (P < or = 0.03). Low-birth-weight rats exhibit accelerated senescence in kidneys and hearts after rapid catch-up growth, a likely important link between early growth and subsequent hypertension, renal, and cardiovascular disease.
authors.affiliation: Division of Nephrology, University of Alberta, Edmonton, Alberta, Canada. vluyckx@ualberta.ca
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Luyckx
authors.forename: Catharine A
authors.initials: CA
authors.lastname: Compston
authors.forename: Thomas
authors.initials: T
authors.lastname: Simmen
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Mueller
mesh_terms: D000375:Aging / Q000378:metabolism; D019588:Aging, Premature / Q000150:complications*; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D015415:Biomarkers / Q000378:metabolism; D001724:Birth Weight; D002318:Cardiovascular Diseases / Q000209:etiology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004032:Diet; D002149:Energy Intake; D005260:Female; D015870:Gene Expression; D007668:Kidney / Q000254:growth & development* / Q000378:metabolism; D007674:Kidney Diseases / Q000209:etiology*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D055765:Shc Signaling Adaptor Proteins / Q000378:metabolism; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1
chemical_list: D015415:Biomarkers; D019941:Cyclin-Dependent Kinase Inhibitor p16; D017382:Reactive Oxygen Species; D016160:Retinoblastoma Protein; D055765:Shc Signaling Adaptor Proteins; C528035:Shc1 protein, rat; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D010088:Oxidoreductases