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  • 1
    Keywords: SINGLE-NUCLEOTIDE POLYMORPHISMS ; Longevity ; two-stage analysis ; Multilocus
    Abstract: The pathways that regulate energy homeostasis, the mechanisms of damage repair, and the signaling response to internal environmental changes or external signals have been shown to be critical in modulating lifespan of model organisms and humans. In order to investigate whether genetic variation of genes involved in these pathways contribute to longevity, a two-stage case-control study in two independent sets of long-lived individuals from Calabria (Italy) was performed. In stage 1, 317 SNPs in 104 genes were analyzed in 78 cases (median age 98 years) and 71 controls (median age 67 years). In stage 2, 31 candidate SNPs identified in stage 1 (pi (markers) = 0.1) were analyzed in an independent sample composed by 288 cases (median age 92 years) and 554 controls (median age 67 years). Two SNPs, rs282070 located in intron 1 of the MAP3K7 gene, and rs2111699 located in intron 1 of the GSTZ1 gene, were significantly associated (after adjustment for multiple testing) with longevity in stage 2 (p = 1.1 x 10(-3) and p = 1.4 x 10(-3), respectively). Interestingly, both genes are implicated in the cellular response to internal and external environmental changes, playing a crucial role in the inflammation processes that accompany aging. Our data confirm that long-lived subjects are endowed with genetic variants that allow them to optimize these cellular responses and to better deal with environmental and internal stresses.
    Type of Publication: Journal article published
    PubMed ID: 22576335
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Age 1 (1978), S. 17-20 
    ISSN: 1574-4647
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Concentrations below 13.6 mM centrophenoxine in the culture medium had no inhibitory effect on several developmental parameters of Caenorhabditis briggsae: specifically growth, fecundity and longevity. The effects on two parameters which characterize senescence in this nematode, increased osmotic fragility and increased specific gravity, were also evaluated. Above 6.8 mM old nematodes showed significantly less osmotic fragility and reduced specific gravity. Evaluation of the effects on negative charge of the cuticle surface membrane showed that neither 6.8 mM nor 17 mM affected negative surface charge density. Electron microscope studies showed that age-pigment accumulation was significantly retarded by a concentration of 6.8 mM centro-phenoxine. It is suggested that the specific gravity effect is correlated with the retardation of lipofuscin accumulation with age. If this proves correct, then specific gravity will be another parameter for measuring the effects of centrophenoxine on aging tissues. This study also demonstrated that the effects of drugs on the retardation of age pigment formation can be visualized in three weeks by utilizing C. briggsae as a model.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Age 1 (1978), S. 24-24 
    ISSN: 1574-4647
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1574-4647
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fluorescence and respiratory properties of rat liver mitochondrial membranes in young and old animals have been measured. A trend toward decreasing specific activity of malate + glutamate supported state 4 respiration in mitochondria from 18 month old animals as compared to 1 month old animals is found. A concomitant decrease in membrane protein tryptophane fluorescence and an increase in a membrane fluorophore proposed to be aminoiminopropene has also been observed using nanosecond fluorescence spectroscopy techniques.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1574-4647
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purified bovine erythrocyte superoxide dismutase (SOD) was separated by polyacrylamide gel electrophoresis. Gels which were stained for protein showed a single major band (Rx-0.41). Gels which were stained for SOD activity showed a single achromatic band (Rx-0.41) and gels which were stained for dopa oxidase activity also showed a single grey-black band (Rx-0.41). Rx values of other oxidases (horseradish peroxidase, mushroom tyrosinase, catalase and melanoma “tyrosinase” (L-dopa Oxidase) were significantly different from that of SOD. The dopa oxidase activity of SOD may be important as an alternative pathway for melanin synthesis with resultant free radical quenching by melanin and its intermediates. This secondary function is in addition to its primary function as a superoxide dismutase. These functions may be interrelated in some circumstances when L-dopa acts as the proton donor of the dismutase reaction: .
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1574-4647
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Male and female rats were fed 40% of calories as beef tallow (BT) (polyunsaturated to saturated (P:S) fatty acid ratio = 0.17) or a mix of safflower oil and beef tallow to give a P:S of 0.94 (M) in a nutritionally complete diet. Groups were killed at 9, 12, 15, 18, and 21 months of age and fatty acid and cholesterol concentration and synthesis in liver in vivo were measured. Serum cholesterol concentration and appearance of newly synthesized lipid were also determined. Serum cholesterol concentration increased with age regardless of diet. Fatty acid synthesis from alanine was generally similar to that reported for acetate in response to variables, being higher in females than males and in males consuming BT diet than those consuming M diet. Cholesterol synthesis from alanine was similar to that reported from acetate with regard to sex effect (females higher than males), but did not differ in response to diet. The latter is contrary to reports for acetate incorporation, which has been higher for more polyunsaturated dietary fats. Female rats exhibited very high rates of incorporation of alanine into both fatty acids and cholesterol at 12–18 months of age when they were fed beef tallow. This effect was not observed in females fed mixed fat nor in males. The 21 month old BT females had alanine incorporation rates more like the rats at early ages. This decline at advanced age may be the result of death of those with high synthesis rates and survival of those with lower rates.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1574-4647
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Studies on enzyme changes during aging from rodents, nematodes and tissue culture cells have been reviewed. In the rodent and tissue culture studies, conflicting results on aging of specific enzymes have been reported from several laboratories. These works have been analyzed, with the aim of stressing the different findings and analyzing possible reasons for the discrepancies. With regard to the nematode studies, the authors suggest that the examination of the concept of general failure of protein synthesis mechanisms as a basic cause of cellular senescence requires more rigorous methods than have been utilized in previous studies.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Age 1 (1978), S. 79-79 
    ISSN: 1574-4647
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1574-4647
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats of both sexes were fed diets containing 21% (wt) fat as beef tallow (BT), safflower oil (SO), or a 60:40 BT:SO mix (M). Some of each group were killed at 9, 12, 15, 18, and 21 months of age. Death by 15 months was significantly (P〈.001) greater in SO rats than in other groups. Mortality in SO females was significantly (P〈.005) greater than in SO males. A trend for longer life existed in M compared to BT rats. Platelet aggregation microscopically visible in the alveoli of SO males and thrombi in the pulmonary arteries of SO females suggest that death in these animals may have been related to dietary linoleate. Excessive production of prostaglandins may have induced platelet aggregation and possibly interfered with normal immune responses. Myocardial stellate scars were seen earlier in M males than in other groups. Areas of massive infarction and subsequent fibrosis of the heart were present in BT rats and M males at 15 months but not until 18 months in M females.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Age 1 (1978), S. 117-117 
    ISSN: 1574-4647
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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