Ethical aspects of aging research

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First evaluation of pesticides occurrence in groundwater of Tidone Valley, an area with intensive viticulture.

Abstract Agricultural practice often involves an intensive and incorrect use of pesticides and fertilizers. These chemicals can leach through the soil profile and contaminate groundwater, including drinking water. For this reason, an effective groundwater monitoring is strongly advisable. The aim of this study was to investigate the groundwater contamination by plant protection products (PPPs) on a hilly area situated in the Tidone Valley, North-West of Italy, a region characterized by an intensive viticulture production. This area is not included in the national groundwater monitoring plan and therefore scarce information is available regarding the quality of groundwater, even though the local Environmental Agency previously revealed the occurrence of PPPs at values higher than the Environmental Quality Standard downstream this area. Hence, a monitoring wells network was developed following an upstream-downstream criterion, a list of pesticides to be monitored, based on a multi-actor approach, and an analytical method for PPPs detection and quantification. The analytical approach involved solid phase extraction followed by High-Performance Liquid Chromatography tandem mass spectrometry. The results of three monitoring campaigns revealed the occurrence of seven PPPs at a level higher than EQS for groundwater (0.1 μg/L) in 30% of the wells. The main pesticides detected were Chlorantraniliprole, Dimethomorph, Fluopicolide, Metalaxyl-M, Penconazole, and Tetraconazole, all commonly used in viticulture, together with S-metolachlor, authorized for cereal cropping. Statistical analysis revealed a significant influence of the sampling time, slope of the soil surrounding the wells, wells depth and wells location on the concentration of five PPPs. Therefore, the results obtained show that the improper use of PPPs for grapevine cultivation may cause groundwater contamination and suggest the need for a deeper analysis of territorial reality, including hydrology studies and farmer behavior and for an urgent introduction of best management practices and mitigation measures to promote a sustainable use of PPPs in viticulture

DNA hydroxymethylation levels are altered in blood cells from Down syndrome persons enrolled in the MARK-AGE project

Down syndrome (DS) is caused by the presence of part or an entire extra copy of chromosome 21, a phenomenon that can cause a wide spectrum of clinically defined phenotypes of the disease. Most of the clinical signs of DS are typical of the ageing process including dysregulation of immune system. Beyond the causative genetic defect, DS persons display epigenetic alterations, particularly aberrant DNA methylation patterns that can contribute to the heterogeneity of the disease. In the present work we investigated the levels of 5-hydroxymethylcytosine (5hmC) and of the TET dioxygenase enzymes, which are involved in DNA demethylation processes and are often deregulated in pathological conditions as well as in ageing. Analyses were carried out on peripheral blood mononuclear cells of DS volunteers enrolled in the context of the MARK-AGE study, a large-scale cross-sectional population study with subjects representing the general population in eight European countries. We observed a decrease of 5hmC, TET1 and other components of the DNA methylation/demethylation machinery in DS subjects, indicating that aberrant DNA methylation patterns in DS, which may have consequences on the transcriptional status of immune cells, may be due to a global disturbance of methylation control in DS

Multi-actor approach and engagement strategy to promote the adoption of best management practices and a sustainable use of pesticides for groundwater quality improvement in hilly vineyards.

The adoption of pesticide mitigation measures and innovation at farm level, are seen as a drivers to reach the sustainable water policy objectives. With the aim to prevent the pesticide pressure of hilly vineyards on groundwater contamination, a stepwise approach in Tidone Valley was applied using different consultation mechanisms and involvement strategies throughout the overall process. Face to face meetings, direct surveys, participatory monitoring and planning of several activities aiming to inform, educate, improve skills, change of individual behaviour or raise awareness, or even initiatives to build institutional trust or support for new investment in innovation are some examples. These activities allowed us to involve key actors of water use and governance (such as farmers, advisors, representatives of drinking water management, farmer's associations, Winemaking cooperatives, local Health Authority), and to have a deeper knowledge of the context agricultural practices, of farmer's knowledge and skills concerning factors influencing water contamination and also to promote the most suitable Best Management Practices aimed at limiting the pesticide occurrence in groundwater. Indeed, the surveys results highlighted that the majority of the farms are small (64% of vineyards10 ha), that most of the farmers (62%) are not aware of the current legislation on water, even if 64% of them declare to participate regularly to training courses for the prevention of water contamination and that there is a low to moderate level of adoption of Best Practices able to prevent contamination by pesticides. At the end of the overall process, it can be stated that the multi-actor approach and engagement strategy adopted were successful in improving attitudes to more sustainable practices. This is supported also by the monitoring data that show in 2019 a decrease by 44% of pesticides occurrences and a fall by 68% of values above EQ

Mediterranean diet and inflammaging within the hormesis paradigm

A coherent set of epidemiological data shows that the Mediterranean diet has beneficial effects capable of preventing a variety of age-related diseases in which low-grade, chronic inflammation/inflammaging plays a major role, but the underpinning mechanism(s) is/are still unclear. It is suggested here that the Mediterranean diet can be conceptualized as a form of chronic hormetic stress, similar to what has been proposed regarding calorie restriction, the most thoroughly studied nutritional intervention. Data on the presence in key Mediterranean foods of a variety of compounds capable of exerting hormetic effects are summarized, and the mechanistic role of the nuclear factor erythroid 2 pathway is highlighted. Within this conceptual framework, particular attention has been devoted to the neurohormetic and neuroprotective properties of the Mediterranean diet, as well as to its ability to maintain an optimal balance between pro- and anti-inflammaging. Finally, the European Commission-funded project NU-AGE is discussed because it addresses a number of variables not commonly taken into consideration, such as age, sex, and ethnicity/ genetics, that can modulate the hormetic effect of the Mediterranean diet

Invariant NKT cells contribute to chronic lymphocytic leukemia surveillance and prognosis

Chronic lymphocytic leukemia (CLL) is characterized by the expansion of malignant CD5(+) B lymphocytes in blood, bone marrow and lymphoid organs. CD1d-restricted invariant Natural Killer T (iNKT) cells are innate-like T lymphocytes strongly implicated in tumor surveillance. We investigated the impact of iNKT cells in the natural history of the disease both in Eμ;-Tcl1 (Tcl1) CLL mouse model and 68 CLL patients. We found that Tcl1-CLL cells express CD1d and iNKT cells critically delay the disease onset, but become functionally impaired upon disease progression. In patients, disease progression correlates also with high CD1d expression on CLL cells and impaired iNKT cells. Conversely, disease stability correlates with negative/low CD1d expression on CLL cells and normal iNKT cells, suggesting an indirect leukemia control. iNKT cells indeed hinder CLL survival in vitro by restraining CD1d-expressing Nurse Like Cells, a relevant pro-leukemia macrophage population. Finally, multivariate analysis identifies iNKT cell frequency as independent predictor of disease progression. Together, these results support iNKT cell contribution to CLL immune-surveillance and highlight iNKT cell frequency as prognostic marker for disease progression

Menopause and adipose tissue : miR-19a-3p is sensitive to hormonal replacement

Tissue-specific effects of 17 beta-estradiol are delivered via both estrogen receptors and microRNAs (miRs). Menopause is known to affect the whole-body fat distribution in women. This investigation aimed at identifying menopause-and hormone replacement therapy (HRT)-associated miR profiles and miR targets in subcutaneous abdominal adipose tissue and serum from the same women. A discovery phase using array technology was performed in 13 women, including monozygotic twin pairs discordant for HRT and premenopausal young controls. Seven miRs, expressed in both adipose tissue and serum, were selected for validation phase in 34 women from a different cohort. An age/menopause-related increase of miRs-16-5p, -451a, -223-3p, -18a-5p, -19a-3p,-486-5p and -363-3p was found in the adipose tissue, but not in serum. MiR-19a-3p, involved in adipocyte development and estrogen signaling, resulted to be higher in HRT users in comparison with non-users. Among the identified targets, AKT1, BCL-2 and BRAF proteins showed lower expression in both HRT and No HRT users in comparison with premenopausal women. Unexpectedly, ESR1 protein expression was not modified although its mRNA was lower in No HRT users compared to premenopausal women and HRT users. Thus, both HRT and menopause appear to affect adipose tissue homeostasis via miR-mediated mechanism.Peer reviewe

Cross-sectional analysis of the correlation between daily nutrient intake assessed by 7-day food records and biomarkers of dietary intake among participants of the NU-AGE study

Methods for measuring diet composition and quantifying nutrient intake with sufficient validity are essential to study the association between nutrition and health outcomes and risk of diseases. 7-day food records provides a quantification of food actually and currently consumed and is interesting for its use in intervention studies to monitor diet in a short-term period and to guide participants toward changing their intakes. The objective of this study is to analyze the correlation/association between the daily intake of selected nutrients (collected by a 7-day food records plus a mineral/vitamin supplementation questionnaire) and estimates of energy expenditure as well as blood and urine biomarkers of dietary intakes in 1,140 healthy elderly subjects (65–79 years) at baseline of the NU-AGE intervention study (NCT01754012, clinicaltrials.gov). The results show that: the daily intake of energy correlated significantly with predicted total energy expenditure (pTEE) (ρ = 0.459, p < 0.001, and q < 0.001); protein intake correlated significantly with the ratio of 24 h urinary urea to creatinine excretion (ρ = 0.143 for total protein intake, ρ = 0.296 for animal protein intake, and ρ = 0.359 for protein intake/body weight, p < 0.001 and q < 0.001 for each correlation); vitamin B12 and folate intakes correlated significantly with their serum concentrations (ρ = 0.151 and ρ = 0.363, respectively; p < 0.001 and q < 0.001 for each correlation); sodium and potassium intakes correlated significantly with their 24 h urinary excretion (ρ = 0.298 and ρ = 0.123, respectively; p < 0.001 and q < 0.001 for each correlation); vitamin B12 and folate intakes were negatively associated with plasma homocysteine measure (p = 0.001 and p = 0.004, respectively); stratifying subjects by gender, the correlations between energy intake and pTEE and between potassium intake and its 24 h urinary excretion lost their significance in women. Even if the plasma and urinary levels of these nutrients depend on several factors, the significant correlations between daily reported intake of nutrients (protein, vitamin B12, folate, and sodium) and their blood/urinary markers confirmed that the 7-day food records (plus a supplementation questionnaire) provides reliable data to evaluate short-term current dietary intake in European elderly subjects and it can be exploited to guide and monitor NU-AGE participants through the shift of their diet according NU-AGE recommendations

Mitochondrial DNA involvement in human longevity

AbstractThe main message of this review can be summarized as follows: aging and longevity, as complex traits having a significant genetic component, likely depend on a number of nuclear gene variants interacting with mtDNA variability both inherited and somatic. We reviewed the data available in the literature with particular attention to human longevity, and argued that what we hypothesize for aging and longevity could have a more general relevance and be extended to other age-related complex traits such as Alzheimer's and Parkinson's diseases. The genetics which emerges for complex traits, including aging and longevity, is thus even more complicated than previously thought, as epistatic interactions between nuclear gene polymorphisms and mtDNA variability (both somatic and inherited) as well as between mtDNA somatic mutations (tissue specific) and mtDNA inherited variants (haplogroups and sub-haplogroups) must be considered as additional players capable of explaining a part of the aging and longevity phenotype. To test this hypothesis is one of the main challenge in the genetics of aging and longevity in the next future