Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent findings demonstrate that nutrition during the fetal and neonatal periods can affect the life span of an organism. Our previous studies in rodents using a maternal low protein diet have shown that limiting protein and growth during lactation [postnatal low protein (PLP group)] increases longevity, while in utero growth restriction (IUGR) followed by "catch up growth" (recuperated group) shortens life span. The aim of this study was to investigate mechanisms in early postnatal life that could underlie these substantial differences in longevity. At weaning, PLP animals had improved insulin sensitivity as suggested by lower concentrations of insulin required to maintain concentrations of glucose similar to those of the control group and significant upregulation of insulin receptor-beta, IGF-1 receptor, Akt1, Akt2, and Akt phosphorylated at Ser 473 in the kidney. These animals also had significantly increased SIRT1 (mammalian sirtuin) expression. Expression of the antioxidant enzymes catalase, CuZnSOD, and glutathione peroxidase-1 was elevated in these animals. In contrast, recuperated animals had a significantly increased fasting glucose concentration, while insulin levels remained comparable to those of the control group suggesting relative insulin resistance. MnSOD expression was increased in these animals. These data suggest that early nutrition can lead to alterations in insulin sensitivity and antioxidant capacity very early in life, which may influence life span.
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PMID:Maternal protein restriction leads to early life alterations in the expression of key molecules involved in the aging process in rat offspring. 1809 69

The hormetic effect, which extends the lifespan by various stressors, has been confirmed in Caenorhabditis elegans (C. elegans). We have previously reported that oxidative stress resistance in a long-lived mutant age-1 is associated with the hormesis. In the age-1 allele, which activates an insulin/insulin-like growth factor-1 (Ins/IGF-1) signaling pathway, the superoxide dismutase (SOD) and catalase activities increased during normal aging. We now demonstrate changes in the mitochondrial superoxide radical (*O(2)(-)) levels of the hormetic conditioned age-related strains. The *O(2)(-) levels in age-1 strain significantly decreased after intermittent hyperoxia exposure. On the other hand, this phenomenon was not observed in a daf-16 null mutant. This hormesis-dependent reduction of the *O(2)(-) levels was observed even if the mitochondrial Mn-SOD was experimentally reduced. Therefore, it is indicated that the hormesis is mediated by events that suppress the mitochondrial *O(2)(-) production. Moreover, some SOD gene expressions in the hormetic conditioned age-1 mutant were induced over steady state mRNA levels. These data suggest that oxidative stress-inducible hormesis is associated with a reduction of the mitochondrial *O(2)(-) production by activation of the antioxidant system via the Ins/IGF-1 signaling pathway.
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PMID:Hyperoxia exposure induced hormesis decreases mitochondrial superoxide radical levels via Ins/IGF-1 signaling pathway in a long-lived age-1 mutant of Caenorhabditis elegans. 1828 59

Muscle atrophy is a highly prevalent condition among older adults, and results from reduced muscle mass and fiber cross-sectional area. Resistive exercise training and moderate (30-40%) caloric restriction may reduce the rate of sarcopenia in animal models. We tested the hypothesis that lifelong, voluntary exercise combined with mild (8%) caloric restriction would attenuate the reduction of muscle fiber cross-sectional area in the rat plantaris. Fischer-344 rats were divided into: young adults (6 mo) fed ad libitum (YAL); 24 mo old fed ad libitum (OAL); 24 mo old on 8% caloric restriction (OCR); lifelong wheel running with 8% CR (OExCR). Plantaris fiber cross-sectional area was significantly lower in OAL than YAL (-27%), but protected in OCR and OExCR, while mass/body mass ratio was preserved in OExCR only. Furthermore, 8% CR and lifelong wheel running attenuated the age-induced increases in extramyocyte space and connective tissue. Citrate synthase activity decreased with age, but was not significantly protected in OCR and OExCR. Total hydroperoxides were higher in OAL than YAL, but were not elevated in OExCR, with out a change in MnSOD. IGF-1 levels were lower in OAL (-57%) than YAL, but partially protected in the OExCR group (+51%).
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PMID:Lifelong exercise and mild (8%) caloric restriction attenuate age-induced alterations in plantaris muscle morphology, oxidative stress and IGF-1 in the Fischer-344 rat. 1831 75

Advanced age is a major risk factor for atherosclerosis, but how aging per se influences pathogenesis is not clear. Insulin-like growth factor-1 receptor (IGF-1R) promotes aortic vascular smooth muscle cell (VSMC) growth, migration, and extracellular matrix formation, but how IGF-1R signaling changes with age in VSMC is not known. We previously found age-related differences in the activation of Akt/FOXO3a and ERK1/2 pathways in VSMC, but the upstream signaling remains unclear. Using explanted VSMC from Fischer 344/Brown Norway F1 hybrid rats shown to display age-related vascular pathology similar to humans, we compared IGF-1R expression in early passages of VSMC and found a constitutive activation of IGF-1R in VSMC from old compared to young rats, including IGF-1R expression and its tyrosine kinase activity. The link between IGF-1R activation and the Akt/FOXO3a and ERK pathways was confirmed through the induction of IGF-1R with IGF-1 in young cells and attenuation of IGF-1R with an inhibitor in old cells. The effects of three kinase inhibitors: AG1024, LY294002, and TCN, were compared in VSMC from old rats to differentiate IGF-1R from other upstream signaling that could also regulate the Akt/FOXO and ERK pathways. Genes for p27kip-1, catalase and MnSOD, which play important roles in the control of cell cycle arrest and stress resistance, were found to be FOXO3a-targets based on FOXO3a-siRNA treatment. Furthermore, IGF-1R signaling modulated these genes through activation of the Akt/FOXO3a pathway. Therefore, activation of IGF-1R signaling influences VSMC function in old rats and may contribute to the increased risk for atherosclerosis.
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PMID:Age-related differences in insulin-like growth factor-1 receptor signaling regulates Akt/FOXO3a and ERK/Fos pathways in vascular smooth muscle cells. 1861 85