scholarly journals Reconciling the clk-1 and aging paradox and categorizing lifespan curves by taking individual specificity into account

2017 ◽  
Author(s):  
Yaguang Ren ◽  
Congjie Zhang ◽  
Wenxuan Guo ◽  
Chao Zhang

AbstractThe clk-1 gene encodes the demethoxyubiquinone (DMQ) hydroxylase that is required for biosynthesis of ubiquinone (coenzyme Q). Deletion of clk-1 was lethal in mice, and its mutation in C. elegans mildly extended lifespan, slowed physiological rate and led to sickness. We found that if growth retardation was taken into account the average lifespan of clk-1 mutants would not be prolonged or would be shortened. In addition, recent study showed that knocking down of clk-1 shortened lifespan. Although the extension of lifespan in clk-1 mutants was mild and was not observed sometimes, some progenies indeed had prolonged maximum lifespan even if retardation of growth was taking into account. These paradoxes implicate the existence of individual specificity in the aging process even in the same cohort, just like a drug is beneficial for some people while for others it is detrimental. We further categorized lifespan curves into five kinds of patterns according to the lifespan alternations observed in organisms: N (normal); L (long-lived); S (short-lived); F (flattened); ST (steepened), and found that the curve of clk-1 mutants fit into the F pattern. The reasons behind the individual specificity and its implications in aging process deserves further investigations.

2013 ◽  
Vol 394 (5) ◽  
pp. 631-639 ◽  
Author(s):  
Maria Luisa Genova ◽  
Giorgio Lenaz

Abstract Substantial evidence exists that the mitochondrial respiratory chain is organized in supramolecular units called supercomplexes or respirasomes. While the structural evidence of the supercomplexes is overwhelming, fewer studies have focused on their functional relevance. Although the presence of coenzyme Q channeling between complexes I and III has been ascertained, no such clear demonstration has been carried out for cytochrome c between complexes III and IV, at least in mammalian mitochondria. This review also discusses the implications concerning the number of respiratory complexes organized in supercomplexes and the possibility that they represent associations in dynamic equilibrium with the individual complexes.


2021 ◽  
Vol 12 ◽  
Author(s):  
Serena Dato ◽  
Paolina Crocco ◽  
Nicola Rambaldi Migliore ◽  
Francesco Lescai

BackgroundAging is a complex phenotype influenced by a combination of genetic and environmental factors. Although many studies addressed its cellular and physiological age-related changes, the molecular causes of aging remain undetermined. Considering the biological complexity and heterogeneity of the aging process, it is now clear that full understanding of mechanisms underlying aging can only be achieved through the integration of different data types and sources, and with new computational methods capable to achieve such integration.Recent AdvancesIn this review, we show that an omics vision of the age-dependent changes occurring as the individual ages can provide researchers with new opportunities to understand the mechanisms of aging. Combining results from single-cell analysis with systems biology tools would allow building interaction networks and investigate how these networks are perturbed during aging and disease. The development of high-throughput technologies such as next-generation sequencing, proteomics, metabolomics, able to investigate different biological markers and to monitor them simultaneously during the aging process with high accuracy and specificity, represents a unique opportunity offered to biogerontologists today.Critical IssuesAlthough the capacity to produce big data drastically increased over the years, integration, interpretation and sharing of high-throughput data remain major challenges. In this paper we present a survey of the emerging omics approaches in aging research and provide a large collection of datasets and databases as a useful resource for the scientific community to identify causes of aging. We discuss their peculiarities, emphasizing the need for the development of methods focused on the integration of different data types.Future DirectionsWe critically review the contribution of bioinformatics into the omics of aging research, and we propose a few recommendations to boost collaborations and produce new insights. We believe that significant advancements can be achieved by following major developments in bioinformatics, investing in diversity, data sharing and community-driven portable bioinformatics methods. We also argue in favor of more engagement and participation, and we highlight the benefits of new collaborations along these lines. This review aims at being a useful resource for many researchers in the field, and a call for new partnerships in aging research.


1992 ◽  
Vol 8 (S1) ◽  
pp. 176-181 ◽  
Author(s):  
Ingemar Leijon

AbstractIntrauterine growth retardation is associated with high risk of perinatal asphyxia. The neonatal mortality rate of small-for-gestational-age (SGA) infants (birthweight ≤ 2 SD) in Sweden decreased from 5.6% in 1973 to 2.0% in 1987. During the same period, the number SGA infants with postnatal asphyxia (5 min Apgar score <7) decreased from 10% to 5%. Based on antenatal diagnosis of fetal growth retardation, an optimal time of delivery reduces the risk of major neurological and developmental sequelae of the individual infant.


2001 ◽  
Vol 2001 (1) ◽  
Author(s):  
J. Maynard Smith

Aging processes are defined as those that increase the susceptibility of individuals as they grow older to the factors that may cause death. Various possible theories of aging are considered, and evidence that may help to decide between them is discussed. Changes in different organ systems may be merely symptoms of some single aging process, or they may be largely independent and synchronized by natural selection. Even if different organ systems age independently, they may do so as a result of similar changes at a cellular level. Cellular theories of aging may have to take into account the effects of selection between the cells in a tissue. The effects of radiation and somatic mutation theories of aging are discussed. It is suggested that radiation shortens life by inducing somatic mutations but that normal aging is not to any important extent caused by somatic mutations, although it may result from changes in cells that have effects on the physiology of the individual similar to those of somatic mutations. Evidence is presented that in Drosophila and in mice there are two phases in the life-span. In Drosophila , there is an initial “aging” phase, which is irreversible and occurs at a rate approximately independent of temperature, and a second “dying” phase, which is temperature-dependent in rate and reversible at lower temperatures. Reproduced by permission. J. Maynard Smith, Review Lectures on Senescence: I. The Causes of Aging. Proc. R. Soc. London Ser. B 157 , 115-127 (1962).


2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Zhaokang Zhang ◽  
Yannan Zhou ◽  
Haitao Fan ◽  
Kirunda John Billy ◽  
Yunjie Zhao ◽  
...  

As the global population ages, searching for drugs and functional foods which can slow down the aging process has attracted a number of researchers. In this paper, the Lycium barbarum polysaccharides (LBP) extracted from Lycium barbarum was characterized and the effects of LBP on the aging and health of C. elegans were studied. Results showed that LBP can prolong the lifespan, improve the abilities to withstand environmental stress, enhance reproductive potentials, and maintain muscle integrity of C. elegans. By using genetically mutated C. elegans strains, RNAi gene silencing, and measuring the mRNA expression level, it was demonstrated that the lifespan of C. elegans was extended by LBP mainly through sir-2.1, daf-12, and daf-16. The present study might provide a basis for further study of LBP as a food or drug to interfere with aging and reduce the incidence of age-related diseases.


2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Alexis V. Stutzman ◽  
April S. Liang ◽  
Vera Beilinson ◽  
Kohta Ikegami

Abstract Background Chromatin organization is central to precise control of gene expression. In various eukaryotic species, domains of pervasive cis-chromatin interactions demarcate functional domains of the genomes. In nematode Caenorhabditis elegans, however, pervasive chromatin contact domains are limited to the dosage-compensated sex chromosome, leaving the principle of C. elegans chromatin organization unclear. Transcription factor III C (TFIIIC) is a basal transcription factor complex for RNA polymerase III, and is implicated in chromatin organization. TFIIIC binding without RNA polymerase III co-occupancy, referred to as extra-TFIIIC binding, has been implicated in insulating active and inactive chromatin domains in yeasts, flies, and mammalian cells. Whether extra-TFIIIC sites are present and contribute to chromatin organization in C. elegans remains unknown. Results We identified 504 TFIIIC-bound sites absent of RNA polymerase III and TATA-binding protein co-occupancy characteristic of extra-TFIIIC sites in C. elegans embryos. Extra-TFIIIC sites constituted half of all identified TFIIIC binding sites in the genome. Extra-TFIIIC sites formed dense clusters in cis. The clusters of extra-TFIIIC sites were highly over-represented within the distal arm domains of the autosomes that presented a high level of heterochromatin-associated histone H3K9 trimethylation (H3K9me3). Furthermore, extra-TFIIIC clusters were embedded in the lamina-associated domains. Despite the heterochromatin environment of extra-TFIIIC sites, the individual clusters of extra-TFIIIC sites were devoid of and resided near the individual H3K9me3-marked regions. Conclusion Clusters of extra-TFIIIC sites were pervasive in the arm domains of C. elegans autosomes, near the outer boundaries of H3K9me3-marked regions. Given the reported activity of extra-TFIIIC sites in heterochromatin insulation in yeasts, our observation raised the possibility that TFIIIC may also demarcate heterochromatin in C. elegans.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Yoko Honda ◽  
Yoko Araki ◽  
Taketoshi Hata ◽  
Kenji Ichihara ◽  
Masafumi Ito ◽  
...  

Royal jelly (RJ) produced by honeybees has been reported to possess diverse health-beneficial properties and has been implicated to have a function in longevity across diverse species as well as honeybees. 10-Hydroxy-2-decenoic acid (10-HDA), the major lipid component of RJ produced by honeybees, was previously shown to increase the lifespan ofCaenorhabditis elegans.The objective of this study is to elucidate signaling pathways that are involved in the lifespan extension by 10-HDA. 10-HDA further extended the lifespan of thedaf-2mutants, which exhibit long lifespan through reducing insulin-like signaling (ILS), indicating that 10-HDA extended lifespan independently of ILS. On the other hand, 10-HDA did not extend the lifespan of theeat-2mutants, which show long lifespan through dietary restriction caused by a food-intake defect. This finding indicates that 10-HDA extends lifespan through dietary restriction signaling. We further found that 10-HDA did not extend the lifespan of the long-lived mutants indaf-15, which encodes Raptor, a target of rapamycin (TOR) components, indicating that 10-HDA shared some longevity control mechanisms with TOR signaling. Additionally, 10-HDA was found to confer tolerance against thermal and oxidative stress. 10-HDA increases longevity not through ILS but through dietary restriction and TOR signaling inC. elegans.


1978 ◽  
Vol 89 (4) ◽  
pp. 753-762 ◽  
Author(s):  
Ove Axelsson

ABSTRACT A non-chromatographic radioimmunoassay for estimation of unconjugated oestetrol in plasma from pregnant women is described. The antiserum has a high specificity to oestetrol. The technical procedure is simple and rapid. Only small amounts of plasma (0.2–0.4 ml) are needed for the analysis. The method has been applied to the measurement of oestetrol in plasma from pregnant women before and after an intravenous injection of 50 mg DHAS. In women with uncomplicated pregnancies a rise of plasma oestetrol was found 60 min after the injection. From 120 to 360 min there was a plateau level, at 600 min a decrease from this level was observed. No changes in the oestetrol response were found with advancing gestational age from the 33rd to the 40th week of pregnancy. A great spread in the individual responses were recorded. Patients with pre-eclampsia and intrauterine growth retardation had a tendency to a lower increase and patients with diabetes a tendency to a higher increase of plasma oestetrol after the DHAS administration. From the data obtained it is concluded that the increase of plasma oestetrol after an intravenous injection of DHAS in most cases is secondary to the increase of plasma oestradiol. The results suggest that measurement of unconjugated oestetrol in plasma after an intravenous load of DHAS is no safe way to assess foetal wellbeing. In women with intrauterine growth retardation (IUGR) the simultaneous measurement of plasma oestradiol and oestetrol after an injection of DHAS indicates a possibility to distinguish placental from foetal causes of this syndrome.


Author(s):  
Tatyana MECHKAROVA ◽  
Yaroslav ARGIROV ◽  
Daniela SPASOVA ◽  
Aneliya STOYANOVA

This paper aims to determine the extent of aging of nitrogen ferrite at temperatures below 100 °C and the structural and strength changes that occur in the process. The tests are carried out on samples of technically pure iron (Armco). The specimens are pre-deformed by tension and re-crystallisation heating to achieve a large-grain ferrite structure. A large-grained structure has been chosen to more accurately track the change in micro-hardness of the individual grains during the aging process. Nitric ferrite results from gas carbonitriding and subsequent hardening. Upon hardening, the samples are stored in a refrigerator, and then the surface layer formed is removed through electrochemical corrosion. Afterwards, aging heat treatment at temperatures below 100 °C is undertaken. After the aging process, micro-hardness of the individual grains is examined and X-ray structural analysis is performed.


2018 ◽  
Author(s):  
Nabeel S. Ganem ◽  
Noa Ben-Asher ◽  
Aidan C. Manning ◽  
Sarah N. Deffit ◽  
Michael C. Washburn ◽  
...  

SummaryA-to-I RNA editing is widespread in eukaryotic transcriptomes and plays an essential role in the creation of proteomic and phenotypic diversity. Loss of ADARs, the proteins responsible for A-to-I editing, results in lethality in mammals. In C. elegans, knocking out both ADARs, ADR-1 and ADR-2, results in aberrant behavior and abnormal development. Studies have shown that ADR-2 can actively deaminate dsRNA while ADR-1 cannot. However, as most studies of C. elegans ADARs were performed on worms mutated in both ADAR genes, the effects observed cannot be attributed to a single ADAR or to the interactions between ADAR genes. Therefore, we set to study the effects of each C. elegans ADAR on RNA editing, gene expression, protein levels and the contribution of each of ADAR to the phenotypes observed in worms mutated in both genes, in order to elucidate their distinct functions. We found significant differences in the phenotypes observed in worms mutated in a single ADAR gene. Worms harboring adr-1 mutations have a significant reduction in their lifespan, while worms harboring adr-2 mutations have extended lifespan. We also observed severe abnormalities in vulva formation in adr-1 mutants, and we suggest that these phenotypes are a result of an RNA editing independent function of ADR-1. Mutations in each ADAR resulted in expressional changes in hundreds of genes, and a significant downregulation of edited genes. However, very few changes in the protein levels were observed. In addition, we found that ADR-1 binds many edited genes and primarily promotes editing at the L4 stage of development. While editing still occurs in the absence of ADR-1, most of the editing occurs in genes that are edited in wildtype worms, suggesting that ADR-1 does not prevent editing by binding to and protecting the RNA but rather enhances or promotes editing. Our results suggest that ADR-1 plays a significant role in the RNA editing process and by altering editing levels it causes the severe phenotypes that we observed. In contrast, a complete lack of RNA editing is less harmful to the worms. Furthermore, our results indicate that the effect of RNA editing on the protein content in the cell is minor and probably the main purpose of these modifications is to antagonize or enhance other gene regulatory mechanisms that act on RNA.


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