New molecular biomarkers for early detection and prevention of frailty in older adults

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Life-course exposure and its influence on frailty syndrome

Publication . Lage, Bruna; Costa, Solange; Teixeira, João Paulo

One area of health concern is reducing the burden of environmentally induced disease in populations that may be more susceptible to the effects of exposures to contaminants. The potential to reduce the prevalence of some major diseases is driving research to understand the totality of exposures over the course of our lifetimes. Older adults are well-recognized susceptible subpopulation. Health status in older adults is complex and multidimensional. One metric is frailty, a state of increased vulnerability to stressors, characterized by decreased physical and mental functioning and an increased risk for poor health outcomes. The European Commission has appointed Ageing one of the main priorities in the next Horizon 2020 Framework Program, the prevention of frailty in old age is one of the key actions identified. The aim of the present study is to build and apply a life-course exposure questionnaire and study the association with DNA basal damage and oxidative damage endpoints with frailty syndrome, contributing to the knowledge of the mechanistic pathways and syndrome aetiology. A total of 61 voluntary individuals aged 65 and over were involved in the study from senior recreational community associations and day care centres, located in metropolitan region of Oporto. Frailty assessment was performed using Fried’s frailty model and the individuals were classified as robust, pre-frail or frail. Life-time exposure was evaluated by a selfreported life-course exposure questionnaire and a job exposure matrix application. DNA basal damage and DNA oxidative damage endpoints were measured through comet assay in whole blood. Study population was classified as 47.5% robust, 49.2% pre-frail and 3.3% frail. A relation between the prevalence frailty with age and with gender was observed, with women and older elderly displaying higher rates of frailty. A relation between frailty status and secondhand smokers was found, since higher prevalence of exposure to tobacco smoke was found in pre-frail group (23.3%) when compared with the robust individuals (10.4%). Associations between frailty status and consumption of home-produced vegetables were found, with robust individuals consuming more home-produced vegetables (71.4%) from this source compared to pre-frail individuals (28.6%) that eat those aliments. Furthermore, associations between the consume of these vegetables and DNA damage in robust groups were found, since the robust individuals that include these aliments in their diet showing lower DNA damage than robust individuals that not consumption those aliments from particular produced sources. Regarding the effects of the variables studied, a significant influence was found on the genotoxic endpoints for gender and age within the robust group (p<0.05). Thus, significant differences were observed between the basal damage between robust females and males and between the oxidative damage between earlier age group and 75- 84 age group. Lastly, also a relation was verified between the role of current exposures and the DNA damage, regarding household-proximity to farming operation within the robust group. Thus, robust individuals that reported to live near of this activity have higher basal and oxidative damage than those robust individuals that do not live near farming operations (p<0.05). Data obtained provides preliminary information on relations between exposure, frailty syndrome and DNA damage. Further studies need to be performed in order to deepen the knowledge about frailty aetiology and the possible role of life-course exposures, helping to understand how the past may affect the future.

2017-11-24Master thesis

Open access

Population exposure to particulate-matter and related mortality due to the Portuguese wildfires in October 2017 driven by storm Ophelia

Publication . Augusto, Sofia; Ratola, Nuno; Tarín-Carrasco, Patricia; Jiménez-Guerrero, Pedro; Turco, Marco; Schuhmacher, Marta; Costa, Solange; Teixeira, J.P.; Costa, Carla

In October 2017, hundreds of wildfires ravaged the forests of the north and centre of Portugal. The fires were fanned by strong winds as tropical storm Ophelia swept the Iberian coast, dragging up smoke (together with Saharan dust from north-western Africa) into higher western European latitudes. Here we analyse the long-range transport of particulate matter (PM10) and study associations between PM10 and short-term mortality in the Portuguese population exposed to PM10 due to the October 2017 wildfires, the worst fire sequence in the country over the last decades. We analysed space- and ground-level observations to track the smoke plume and dust trajectory over Portugal and Europe, and to access PM10 concentrations during the wildfires. The effects of PM10 on mortality were evaluated using satellite data for exposure and Poisson regression models. The smoke plume covered most western European countries (including Spain, France, Belgium and the Netherlands), and reached the United Kingdom, where the population was exposed in average to an additional PM10 level of 11.7 µg/m3 during seven smoky days (three with dust) in relation to the reference days (days without smoke or dust), revealing the impact of the wildfires on distant populations. In Portugal, the population was exposed in average to additional PM10 levels that varied from 16.2 to 120.6 µg/m3 in smoky days with dust and from 6.1 to 20.9 µg/m3 in dust-free smoky days. Results suggest that PM10 had a significant effect on the same day natural and cardiorespiratory mortalities during the month of October 2017. For every additional 10 µg/m3 of PM10, there was a 0.89% (95% confidence interval, CI, 0-1.77%) increase in the number of natural deaths and a 2.34% (95% CI, 0.99-3.66%) increase in the number of cardiorespiratory-related deaths. With rising temperatures and a higher frequency of storms due to climate change, PM from Iberian wildfires together with NW African dust will tend to be more often transported into Northern European countries, which may carry health threats to areas far from the ignition sites.

2020-11Journal article

Open access

Potassium bromate as positive assay control for the Fpg-modified comet assay

Publication . Møller, Peter; Muruzabal, Damian; Bakuradze, Tamara; Richling, Elke; Bankoglu, Ezgi Eyluel; Stopper, Helga; Langie, Sabine A.S.; Azqueta, Amaya; Jensen, Annie; Scavone, Francesca; Giovannelli, Lisa; Wojewódzka, Maria; Kruszewski, Marcin; Valdiglesias, Vanessa; Laffon, Blanca; Costa, Carla; Costa, Solange; Teixeira, João Paulo; Marino, Mirko; Del Bo’, Cristian; Riso, Patrizia; Shaposhnikov, Sergey; Collins, Andrew

The comet assay is a popular assay in biomonitoring studies. DNA strand breaks (or unspecific DNA lesions) are measured using the standard comet assay. Oxidative stress-generated DNA lesions can be measured by employing DNA repair enzymes to recognise oxidatively damaged DNA. Unfortunately, there has been a tendency to fail to report results from assay controls (or maybe even not to employ assay controls). We believe this might have been due to uncertainty as to what really constitutes a positive control. It should go without saying that a biomonitoring study cannot have a positive control group as it is unethical to expose healthy humans to DNA damaging (and thus potentially carcinogenic) agents. However, it is possible to include assay controls in the analysis (here meant as a cryopreserved sample of cells i.e. included in each experiment as a reference sample). In the present report we tested potassium bromate (KBrO3) as a positive comet assay control for the formamidopyrimidine DNA glycosylase (Fpg)-modified comet assay. Ten laboratories used the same procedure for treatment of monocytic THP-1 cells with KBrO3 (0.5, 1.5 and 4.5 mM for 1 h at 37°C) and subsequent cryopreservation. Results from one laboratory were excluded in the statistical analysis because of technical issues in the Fpg-modified comet assay. All other laboratories found a concentration-response relationship in cryopreserved samples (regression coefficients from 0.80 to 0.98), although with different slopes ranging from 1.25 to 11.9 Fpg-sensitive sites (%DNA in tail) per 1 mM KBrO3. Our results demonstrate that KBrO3 is a suitable positive comet assay control.

2020-07Journal article

Open access

Exploring Early Detection of Frailty Syndrome in Older Adults: Evaluation of Oxi-Immune Markers, Clinical Parameters and Modifiable Risk Factors

Publication . Teixeira-Gomes, Armanda; Laffon, Blanca; Valdiglesias, Vanessa; Gostner, Johanna M.; Felder, Thomas; Costa, Carla; Madureira, Joana; Fuchs, Dietmar; Teixeira, João Paulo; Costa, Solange

Ageing is accompanied with a decline in several physiological systems. Frailty is an age-related syndrome correlated to the loss of homeostasis and increased vulnerability to stressors, which is associated with increase in the risk of disability, comorbidity, hospitalisation, and death in older adults. The aim of this study was to understand the relationship between frailty syndrome, immune activation, and oxidative stress. Serum concentrations of vitamins A and E were also evaluated, as well as inflammatory biomarkers (CRP and IL-6) and oxidative DNA levels. A group of Portuguese older adults (≥65 years old) was engaged in this study and classified according to Fried's frailty phenotype. Significant increases in the inflammatory mediators (CRP and IL-6), neopterin levels, kynurenine to tryptophan ratio (Kyn/Trp), and phenylalanine to tyrosine ratio (Phe/Tyr), and significant decreases in Trp and Tyr concentrations were observed in the presence of frailty. IL-6, neopterin, and Kyn/Trp showed potential as predictable biomarkers of frailty syndrome. Several clinical parameters such as nutrition, dependency scales, and polypharmacy were related to frailty and, consequently, may influence the associations observed. Results obtained show a progressive immune activation and production of pro-inflammatory molecules in the presence of frailty, agreeing with the inflammageing model. Future research should include different dimensions of frailty, including psychological, social, biological, and environmental factors.

2021-12-10Journal article

Open access

Determining the association between genomic instability and prevalence of frailty syndrome in Portuguese older adults

Publication . Costa, Solange; Gomes, Armanda Teixeira; Lage, Bruna; Esteves, Filipa; Loureiro, A.; Valdiglesias, Vanessa; Laffon, Blanca; Teixeira, João

The aim of the present study was to investigate the association between genomic instability, via DNA damage and oxidative DNA damage, and the prevalence frailty syndrome in a group of older adults community-dwellers (≥ 65 years old).

2020-09Conference object

Restricted access