Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The fidelity of protein synthesis was measured in human diploid skin fibroblasts as a function of passage level ("aging in vitro") and physiological age of tissue donor ("aging in vivo") using two different test systems. First, in cell-free extracts the ratio of delta leu/delta phe incorporation into peptide linkage following in the latter case using cells derived from elderly normal donors and from subjects with the premature aging disorders of Hutchinson-Gilford progeria and the Werner syndrome. Similar results were obtained using a second system of intact cells whereby histidine starvation induces quantifiable satellite spots resolved by two dimensional electrophoresis on polyacrylamide gels on the acidic side of the native actin species due to substitution of the neutral amino acid glutamine for the basic histidine. In fact, error frequencies appeared to decrease during aging in vitro, likely due to selection for clonal subpopulations with the highest fidelity of protein synthesis. The only increases were seen in the intact cell system where SV40-transformed cells showed a three-to-five fold greater error frequency compared to nontransformed fibroblasts. In total, these data fail to support the error catastrophe theory of cellular aging.
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PMID:Protein synthetic fidelity in aging human fibroblasts. 408 61

Reproduction, nutrition and longevity are interrelated phenomena in the evolutionary shaping of living creatures, including man. For example, if nutrition is compromised, reproductive capacity is diminished in order to not threaten the life of a female mammal and her fetus by potential starvation during pregnancy. It has also been shown in both animal models and observational studies of women in historical cohorts that an inverse correlation seems to exist between the number of progeny (children) and longevity. This may represent examples of the so-called "disposable soma hypothesis" as outlined by Kirkwood for the understanding of biological modeling of longevity in relation to reproductive success. The implications of these hypotheses could be found in clinical medicine, e.g. in the understanding of aging processes or reproductive problems. Special attention has been focused on the impact of fetal malnutrition on future risk of biological disturbances, including increased risk of cardiovascular disease, premature aging and cessation of reproductive capacity.
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PMID:[The biological triangle of life. Interaction between nutrition, reproduction and longevity]. 1137 7

Werner syndrome (WS) is a rare autosomal recessive genetic disorder causing premature aging and rare cancers. A gene responsible for WS (WRN) encodes a protein with 1432 amino acids (a.a.) homologous to the E. coli RecQ-type DNA helicase. Transcriptional activation facilitated nucleolar localization of human WRN protein (hWRNp) and serum starvation induced translocation of hWRNp from the nucleoli to the nucleoplasm in human cultured cells, suggesting a nucleolar-nucleoplasm trafficking of hWRNp depending on transcriptional state. Mutant hWRNp lacking the C-terminal 30 a.a. residues (Delta1403-1432) failed to localize in the nucleolus, whereas Delta1405-1432 can migrate into the nucleolus. Here we identify a region putative for nucleolar localization signal (NoLS) containing a sequence of two positively charged amino acids (Arg(1403)-Lys(1404)) in the C-terminal area of hWRNp. By contrast, the mouse homolog (mWRNp) exists only in the nucleoplasm. We show that the inability of mWRNp to migrate into the nucleolus is due to a difference of a sequence in the region corresponding to the NoLS of hWRNp. In addition, mouse cells cannot recognize the NoLS of hWRNp. Our study suggests that defect in nucleolar function of hWRNp may be linked to the premature aging which is not observed in mWRN(-/-) mice.
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PMID:Diverged nuclear localization of Werner helicase in human and mouse cells. 1142 Jun 65

In the yeast Saccharomyces cerevisiae, interventions resembling caloric restriction, either by reduction of glucose or non-essential amino acid content in the medium, prolong life span and retard aging. Here we have examined the role of auxotrophy-complementing amino acid supplementation of S. cerevisiae strains in determining yeast chronological life span and stress resistance. The results obtained from cells cultured in standard amino acid concentrations revealed a reduced final biomass yield and premature aging phenotypes. These included shorter life span and indicators of oxidative stress, together with a G2/M cell cycle arrest and the appearance of a sub-G0/G1 population pointing to the occurrence of a specific cell death programme under starvation of essential amino acids. In order to overcome this starvation, five times higher amino acid concentrations were supplied to the medium as has already been commonly used by few laboratories. Such cultures reached more than five-fold higher final biomass yield in stationary phase and the early aging phenotypes were abrogated. Furthermore, in a long-lived yeast strain lacking TOR1, there was no positive effect of amino acid supplementation on longevity. On the contrary, amino acid supply had a positive effect on chronological life span of RAS2 deleted cells. This study may provide novel insights into the role of essential nutrients and their effect on aging process and raises the warning that the positive effects of caloric restriction on life span maybe restricted to non-essential nutrients. Moreover, the severe consequences on cell physiology, life span and stress resistance induced by essential amino acid imbalances presents a note of caution for those still using standard amino acid concentrations for studies with auxotrophic yeast strains.
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PMID:Low auxotrophy-complementing amino acid concentrations reduce yeast chronological life span. 1754 56

Mutant dwarf and calorie-restricted mice benefit from healthy aging and unusually long lifespan. In contrast, mouse models for DNA repair-deficient progeroid syndromes age and die prematurely. To identify mechanisms that regulate mammalian longevity, we quantified the parallels between the genome-wide liver expression profiles of mice with those two extremes of lifespan. Contrary to expectation, we find significant, genome-wide expression associations between the progeroid and long-lived mice. Subsequent analysis of significantly over-represented biological processes revealed suppression of the endocrine and energy pathways with increased stress responses in both delayed and premature aging. To test the relevance of these processes in natural aging, we compared the transcriptomes of liver, lung, kidney, and spleen over the entire murine adult lifespan and subsequently confirmed these findings on an independent aging cohort. The majority of genes showed similar expression changes in all four organs, indicating a systemic transcriptional response with aging. This systemic response included the same biological processes that are triggered in progeroid and long-lived mice. However, on a genome-wide scale, transcriptomes of naturally aged mice showed a strong association to progeroid but not to long-lived mice. Thus, endocrine and metabolic changes are indicative of "survival" responses to genotoxic stress or starvation, whereas genome-wide associations in gene expression with natural aging are indicative of biological age, which may thus delineate pro- and anti-aging effects of treatments aimed at health-span extension.
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PMID:Delayed and accelerated aging share common longevity assurance mechanisms. 1870 62

Autophagy is an ancient pathway required for cell and tissue homeostasis and differentiation. Initially thought to be a process leading to cell death, autophagy is currently viewed as a beneficial catabolic process that promotes cell survival under starvation conditions by sequestering components of the cytoplasm, including misfolded proteins, protein aggregates, and damaged organelles, and targeting them for lysosome-mediated degradation. In this way, autophagy plays a role in maintaining a balance between degradation and recycling of cellular material. The importance of autophagy is underscored by the fact that malfunctioning of this pathway results in neurodegeneration, cancer, susceptibility to microbial infection, and premature aging. Autophagy occurs in almost all cell types, including immune cells. Recent advances in the field suggest that autophagy plays a central role in regulating the immune system at multiple levels. In this review, we focus on recent developments in the area of autophagy-mediated modulation of immune responses.
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PMID:Autophagy in immune cell regulation and dysregulation. 1967 76

Reduced autophagy may be associated with normal and pathological aging. Here we report a link between autophagy and Werner protein (WRNp), mutated in Werner syndrome, the human premature aging Werner syndrome (WS). WRN mutant fibroblast AG11395 and AG05229 respond weakly to starvation induced autophagy compared to normal cells. While the fusion of phagosomes with lysosome is normal, WS cells contain fewer autophagy vacuoles. Cellular starvation autophagy in WS cells is restored after transfection with full length WRN. Further, siRNA mediated silencing of WRN in the normal fibroblast cell line WI-38 results in decreased autophagy and altered expression of autophagy related proteins. Thus, our observations suggest that WRN may have a role in controlling autophagy and hereby cellular maintenance.
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PMID:Transient overexpression of Werner protein rescues starvation induced autophagy in Werner syndrome cells. 2525 4

Hutchinson-Gilford Progeria Syndrome (HGPS) is a devastating premature aging disease. Mouse models have been instrumental for understanding HGPS mechanisms and for testing therapies, which to date have had only marginal benefits in mice and patients. Barriers to developing effective therapies include the unknown etiology of progeria mice early death, seemingly unrelated to the reported atherosclerosis contributing to HGPS patient mortality, and mice not recapitulating the severity of human disease. Here, we show that progeria mice die from starvation and cachexia. Switching progeria mice approaching death from regular diet to high-fat diet (HFD) rescues early lethality and ameliorates morbidity. Critically, feeding the mice only HFD delays aging and nearly doubles lifespan, which is the greatest lifespan extension recorded in progeria mice. The extended lifespan allows for progeria mice to develop degenerative aging pathologies of a severity that emulates the human disease. We propose that starvation and cachexia greatly influence progeria phenotypes and that nutritional/nutraceutical strategies might help modulate disease progression. Importantly, progeria mice on HFD provide a more clinically relevant animal model to study mechanisms of HGPS pathology and to test therapies.
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PMID:Doubled lifespan and patient-like pathologies in progeria mice fed high-fat diet. 3054 60