The nematode
Caenorhabditis elegans is a popular model organism that is used to study longevity and aging. One drawback of nematode lifespan assays is the labour intensive separation of offspring ...from adults during the reproductive period. To circumvent this, the worm community frequently adds 5-fluoro-2′-deoxyuridine (FUdR), a drug that induces parental sterility, to the nematode culture. Here, we report that FUdR causes a significant artefactual increase in the longevity of
tub-1 mutants which is not observed in wild-type nematodes. This suggests that the effect of FUdR is not neutral and the mechanism of action may result in misleading data, or indeed the misinterpretation of gerontogenes.
Particulate matter (PM) from traffic and other sources has been associated with adverse health effects. One unifying theory is that PM, whatever its source, acts on the human body via its capacity to ...cause damaging oxidation reactions related to its content of pro-oxidants components. Few epidemiological studies have investigated particle oxidative potential (OP) and health. We conducted a time series analysis to assess associations between daily particle OP measures and numbers of deaths and hospital admissions for cardiovascular and respiratory diseases.
During 2011 and 2012 particles with an aerodynamic diameter less than 2.5 and 10μm (PM2.5 and PM10 respectively) were collected daily on Partisol filters located at an urban background monitoring station in Central London. Particulate OP was assessed based on the capacity of the particles to oxidize ascorbate (OPAA) and glutathione (OPGSH) from a simple chemical model reflecting the antioxidant composition of human respiratory tract lining fluid. Particulate OP, expressed as % loss of antioxidant per μg of PM, was then multiplied by the daily concentrations of PM to derive the daily OP of PM mass concentrations (% loss per m3). Daily numbers of deaths and age- and cause-specific hospital admissions in London were obtained from national registries. Poisson regression accounting for seasonality and meteorology was used to estimate the percentage change in risk of death or admission associated with an interquartile increment in particle OP.
We found little evidence for adverse associations between OPAA and OPGSH and mortality. Associations with cardiovascular admissions were generally positive in younger adults and negative in older adults with confidence intervals including 0%. For respiratory admissions there was a trend, from positive to negative associations, with increasing age although confidence intervals generally included 0%.
Our study, the first to analyse daily particle OP measures and mortality and admissions in a large population over two years, found little evidence to support the hypothesis that short-term exposure to particle OP is associated with adverse health effects. Further studies with improved exposure assessment and longer time series are required to confirm or reject the role of particle OP in triggering exacerbations of disease.
Short telomeres are associated with chronic disease and early mortality. Recent studies in adults suggest an association between telomere length and exposure to particulate matter, and that ethnicity ...may modify the relationship. However associations in children are unknown.
We examined associations between air pollution and telomere length in an ethnically diverse group of children exposed to high levels of traffic derived pollutants, particularly diesel exhaust, and to environmental tobacco smoke.
Oral DNA from 333 children (8–9years) participating in a study on air quality and respiratory health in 23 inner city London schools was analysed for relative telomere length using monochrome multiplex qPCR. Annual, weekly and daily exposures to nitrogen oxides and particulate matter were obtained from urban dispersion models (2008–10) and tobacco smoke by urinary cotinine. Ethnicity was assessed by self-report and continental ancestry by analysis of 28 random genomic markers. We used linear mixed effects models to examine associations with telomere length.
Telomere length increased with increasing annual exposure to NOx (model coefficient 0.003, 0.001, 0.005, p<0.001), NO2 (0.009 0.004, 0.015, p<0.001), PM2.5 (0.041, 0.020, 0.063, p<0.001) and PM10 (0.096, 0.044, 0.149, p<0.001). There was no association with environmental tobacco smoke. Telomere length was increased in children reporting black ethnicity (22% 95% CI 10%, 36%, p<0.001)
Pollution exposure is associated with longer telomeres in children and genetic ancestry is an important determinant of telomere length. Further studies should investigate both short and long-term associations between pollutant exposure and telomeres in childhood and assess underlying mechanisms.
•This is the first study on air pollution and telomere length in children.•Genetic ancestry is a major determinant of telomere length in children.•Continuous exposure to pollution is associated with telomere elongation.•Future research should investigate longitudinal effects on telomeres.
•Regeneration within a three-dimensional organ is complex.•Stem cells are an important part of regenerative medicine.•The identification and validation of novel leads will advance the field.•The ...nematode shares conserved signal transduction and regenerative properties.•Caenorhabditis elegans is well positioned to study fundamentals of regenerative medicine.
Stem cell research is a major focus of regenerative medicine, which amalgamates diverse disciplines ranging from developmental cell biology to chemical and genetic therapy. Although embryonic stem cells have provided the foundation of stem cell therapy, they offer an in vitro study system that might not provide the best insight into mechanisms and behaviour of cells within living organisms. Caenorhabditis elegans is a well defined model organism with highly conserved cell development and signalling processes that specify cell fate. Its genetic amenability coupled with its chemical screening applicability make the nematode well suited as an in vivo system in which regenerative therapy and stem cell processes can be explored. Here, we describe some of the major advances in stem cell research from the worm's perspective.
Background: A common link has been exposed, namely, that metal exposure plays a role in obesity and in Parkinson's disease (PD). This link may help to elucidate mechanisms of neurotoxicity. ...Objective: We reviewed the utility of the nematode, Coenorhabditis elegans, as a model organism to study neurodegeneration in obesity and Parkinson's disease (PD), with an emphasis on the neurotransmitter, dopamine (DA). Data sources: A PubMed literature search was performed using the terms "obesity" and any of the following: "C. elegans" "central nervous system," "neurodegeneration," "heavy metals," "dopamine" or "Parkinson's disease." We reviewed the identified studies, including others cited therein, to summarize the current evidence of neurodegeneration in obesity and PD, with an emphasis on studies carried out in C. elegans and environmental toxins in the etiology of both diseases. Data extraction and data synthesis: Heavy metals and DA have both been linked to dietinduced obesity, which has led to the notion that the mechanism of environmentally induced neurodegeneration in PD may also apply to obesity. C. elegans has been instrumental in expanding our mechanism-based knowledge of PD, and this species is emerging as a good model of obesity. With well-established toxicity and neurogenetic assays, it is now feasible to explore the putative link between metal-and chemical-induced neurodegeneration. Conclusions: One side effect of an aging population is an increase in the prevalence of obesity, metabolic disorders, and neurodegenerative orders, diseases that are likely to co-occur. Environmental toxins, especially heavy metals, may prove to be a previously neglected part of the puzzle.
PDF
