Disease relevance of Aging, Premature

• Mutations in WRN result in Werner's syndrome, a disease with symptoms resembling premature aging [1].
• Cockayne syndrome (CS) is a segmental premature aging syndrome in humans that has two complementation groups, CSA and CSB [2].
• To test whether premature aging of mammary epithelial stem cells would have an impact on susceptibility or resistance to mammary cancer, female littermates from FVB/N x WAP-TGF-beta1 mating were injected with mouse mammary tumor virus (MMTV) at 8-10 weeks of age [3].
• Our findings suggest that the 3243 mutation can be associated with mixed clinical features of myoclonic epilepsy with ragged-red fibers (MERRF) and PEO and that a preferential increase in the levels of the mutant mtDNA is not related to graying of hair, and hence to the hypothesized production of premature aging of cells [4].
• Mutations in certain NE proteins are associated with a diversity of human diseases, including muscular dystrophy, neuropathy, lipodistrophy, torsion dystonia and the premature aging condition progeria [5].

Psychiatry related information on Aging, Premature

• In Down's syndrome, the presence of three copies of chromosome 21 is associated with premature aging and progressive mental retardation sharing the pathological features of Alzheimer disease [6].

High impact information on Aging, Premature

• XPF nuclease-dependent telomere loss and increased DNA damage in mice overexpressing TRF2 result in premature aging and cancer [7].
• Werner syndrome (WS) is an uncommon autosomal recessive disorder characterized by premature aging [8].
• Truncation in lamin A causes Hutchinson-Gilford progerial syndrome (HGPS), a severe form of early-onset premature aging [9].
• Growth retardation and premature aging phenotypes in mice with disruption of the SNF2-like gene, PASG [10].
• Mutations in lamins A and C, nuclear intermediate-filament proteins in nearly all somatic cells, cause a variety of diseases that primarily affect striated muscle, adipocytes, or peripheral nerves or cause features of premature aging [11].

Chemical compound and disease context of Aging, Premature

• We discovered this polymorphism when we cloned the mitochondrial manganese-containing superoxide dismutase from cell lines of normal individuals and patients with genetic diseases of premature aging and compared their sequences to each other and to those previously reported [12].
• Brain cell alterations suggesting premature aging induced by dietary deficiency of vitamin B6 and/or copper [13].
• Experiments investigating the effects of endogenous excitatory amino acid antagonists and stimulants of melatonin biosynthesis such as magnesium may finally lead to novel therapeutic approaches for the prevention of degeneration and dysdifferentiation associated with diseases related to premature aging [14].
• It was hypothesized that such glucose-induced premature aging in animals with a genetically restricted potential for beta-cell proliferation could contribute to the precipitation of overt diabetes [15].
• Finally, estradiol has been shown to produce premature aging of the hypothalamic arcuate nucleus, which secretes gonadotropin-releasing hormone [16].

Biological context of Aging, Premature

• Our results indicate that unprocessed prelamin A and truncated lamin A act dominant negatively to perturb DNA damage response and repair, resulting in genomic instability which might contribute to laminopathy-based premature aging [9].
• Werner syndrome (WS) is a human premature aging disorder characterized by chromosomal instability [17].
• We propose instead that respiratory chain dysfunction per se is the primary inducer of premature aging in mtDNA mutator mice [18].
• The premature aging phenotypes in mtDNA mutator mice are thus not generated by a vicious cycle of massively increased oxidative stress accompanied by exponential accumulation of mtDNA mutations [18].
• Werner syndrome (WS) is a premature aging disorder, displaying defects in DNA replication, recombination, repair, and transcription [19].

Anatomical context of Aging, Premature

• Enhanced expression of matrix metalloproteinase (MMP)-1/interstitial collagenase and MMP-3/stromelysin-1 in skin fibroblasts and subsequent damage of dermal connective tissue in the context of sun-induced premature aging and skin tumour progression is causally linked to UVB irradiation [20].
• A decrease in glucose-induced insulin secretion by pancreatic beta-cells and a premature aging of these cells seem to be the main process by which this mutation causes diabetes [21].
• These findings are suggestive of a relationship between premature aging of the dermal elastic fibers and estrogen deprivation [22].
• With regard to the high frequencies, our results suggest that young SLE patients exhibit a "premature aging" of the inner ear which eventually stabilizes [23].
• Excess CuZnSOD generates H2O2 and hydroxyl radicals which affect both NMJ membranes and plasticity, and which may produce premature aging [24].

Gene context of Aging, Premature

• Several other replication mutations, such as rad27 Delta, encoding the FEN-1 nuclease involved in several aspects of genomic stability, also show premature aging [25].
• Late-generation sgs1 and srs2 cells senesce due to apparent premature aging, most likely involving the accumulation of extrachromosomal rDNA circles [26].
• Nijmegen breakage syndrome (NBS) is an autosomal genetic disease demonstrating a variety of phenotypic abnormalities, including premature aging, increased cancer incidence, chromosome instability, and sensitivity to ionizing radiation [27].
• When wrn-1 expression was inhibited by RNA interference (RNAi), a slight reduction in C. elegans life span was observed, with accompanying signs of premature aging, such as earlier accumulation of lipofuscin and tissue deterioration in the head [28].
• The addition of these genes increases the total to five helicase genes in the human RecQ family, which includes helicases involved in Bloom and Werner syndromes, the genetic diseases manifesting the distinctive but overlapping clinical phenotypes of immunodeficiency, premature aging, and an enhanced risk of cancer [29].

Analytical, diagnostic and therapeutic context of Aging, Premature

• To elucidate possible causes of premature aging seen in a strain of senescence-accelerated prone (SAMP8) mice, levels of murine leukemia virus (MuLV) were quantitated in various tissues of SAMP8 by an SC-1/UV plaque assay [30].

References