Action cellulaire de l'acide rétinoique et de la triiodothyronine au corus du vieillissement - Etudes expérimentales et biomédicales

Divers arguments expérimentaux permettent de faire l'hypothèse que des modifications dans le statut nutritionnel et hormonal peuvent être impliquées dans l'apparition des altérations neurobiologiques liées au vieillissement. L'objectif de notre recherche était d'étudier les conséquences du vieillissement sur l'activité des voies de signalisation de l'acide rétinoïque (AR) et de la triiodothyronine (T3). Nous avons d'abord comparé, dans le cerveau de rats, les effets de l'âge et d'une carence en vitamine A sur les activités des voies de signalisation de l'AR et de la T3 et sur certains de leurs gènes cibles impliqués dans les phénomènes de plasticité synaptique. Nos résultats montrent que (i) le vieillissement et la carence vitaminique A entraînent une diminution de l'expression des récepteurs nucléaires de l'AR et de la T3 et de leurs gènes cibles et que (ii) l'administration d'AR ne permet de réactiver que sa propre voie de signalisation; alors que l'administration de T3 est capable de restaurer l'expression de l'ensemble des gènes étudiés. Ces résultats mettent en évidence qu'un niveau optimum d'activité de la voie d'action de la T3 est indispensable au maintien de la fonctionnalité de l'AR. Nous avons ensuite éprouvé cette hypothèse chez l'Homme et étudié les effets du vieillissement et d'une hypothyroïdie sur les voies d'action de l'AR et de la T3 dans les cellules mononucléées du sang. Nos résultats apportent la preuve (i) d'une hypoexpression des récepteurs nucléaires de l'AR et de la T3 liée à l'âge et (ii) qu'une hypothyroïdie s'accompagne d'altérations de la voie d'action de l'AR. Ces données mettent en évidence une diminution de l'activité des voies de signalisation de l'AR et de la T3 chez l'Homme. Nos résultats plaident en faveur de l'hypothèse selon laquelle des dérégulations, même faibles, du niveau d'expression des récepteurs nucléaires pourraient contribuer aux processus de vieillissement de l'individu et aux pathologies qui lui sont associées.Several data allowed to hypothesize that alterations of hormonal and nutritional statutes could be involved in age-related neurobiological damages. The aim of our investigation was to determine the effect of ageing on the vitamin A (retinoic acid, RA) and thyroid hormones (triiodothyronine, T3) signalling pathways. In rat brain, we have first compared the effects of ageing and vitamin A deficiency (VAD) on RA and T3 signalling pathways and on RA and T3 target genes involved in synaptic plasticity. Our results allowed us to demonstrate that (i) RA and T3 signalling pathways (nuclear receptors and target genes) were simultaneously decreased in these situations and that (ii) RA administration was sufficient to regulate its own signalling, whereas T3 administration alone induced normalization of the age-related retinoid and thyroid signalling pathways. These results suggested that an optimal T3 signalling level was required to RA cellular action maintenance. Afterwards, we attempt to test our hypothesis in humans. Two biomedical studies performed on elderly and hypothyroid subjects allowed us to prove (i) a simultaneous hypoexpression of RA and T3 nuclear receptors in peripheral blood mononuclear cells from aged subjects and (ii) that hypothyroidism was a situation in which vitamin A signalling pathway was altered. These data suggested that a down-regulation of RA and T3 signalling occurred with ageing or hypothyroidism in humans. These results provide new arguments about a hypothesis assuming that a slight nuclear receptor down-regulation could contribute to ageing processes and/or age-related pathologies

Nutrients

Vitamin K participates in brain physiology. This study aimed to determine whether using vitamin K antagonists (VKAs), which interfere with the vitamin K cycle, were (i) cross-sectionally associated with altered cognitive performance, and (ii) independent predictors of cognitive changes in older adults over 24 months. Information was collected on the use of VKAs (i.e., warfarin, acenocoumarol, and fluindione) among 378 geriatric outpatients (mean, 82.3 +/- 5.6 years; 60.1% female). Global cognitive performance and executive functions were assessed with Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB) scores, respectively, at baseline and after 12 and 24 months of follow-up. Age, gender, body mass index, mean arterial pressure, disability, gait speed, comorbidities, atrial fibrillation, stroke, carotid artery stenosis, leukoaraiosis grade on computed tomography (CT) scan, psychoactive drugs, antidementia drugs, blood-thinning drugs (i.e., anticoagulants other than VKAs, antiplatelet medications), serum creatinine levels, and vitamin B12 concentrations were considered as potential confounders. Using VKAs was associated with lower (i.e., worse) FAB score at baseline (adjusted beta = -2.1, p = 0.026), and with a decrease in FAB score after 24 months (adjusted beta = -203.6%, p = 0.010), but not after 12 months (p = 0.659). Using VKAs was not associated with any change in MMSE score at baseline (p = 0.655), after 12 months (p = 0.603), or after 24 months (p = 0.201). In conclusion, we found more severe executive dysfunction at baseline and incident executive decline over 24 months among geriatric patients using VKAs, when compared with their counterparts

J Clin Med

Frailty and sarcopenia are characterized by a loss of muscle mass and functionality and are diagnosed mainly by functional tests and imaging parameters. However, more muscle specific biomarkers are needed to improve frailty diagnosis. Plasma 3-methylhistidine (3-MH), as well as the 3-MH-to-creatinine (3-MH/Crea) and 3-MH-to-estimated glomerular filtration rate (3-MH/eGFR) ratios might support the diagnosis of frailty. Therefore, we investigated the cross-sectional associations between plasma 3-MH, 3-MH/Crea and 3-MH/eGFR with the frailty status of community-dwelling individuals (>65 years). 360 participants from two French cohorts of the FRAILOMIC initiative were classified into robust, pre-frail and frail according to Fried's frailty criteria. General linear models as well as bivariate and multiple linear and logistic regression models, which were adjusted for several confounders, were applied to determine associations between biomarkers and frailty status. The present study consisted of 37.8% robust, 43.1% pre-frail and 19.2% frail participants. Frail participants had significantly higher plasma 3-MH, 3-MH/Crea and 3-MH/eGFR ratios than robust individuals, and these biomarkers were positively associated with frailty status. Additionally, the likelihood to be frail was significantly higher for every increase in 3-MH (1.31-fold) and 3-MH/GFR (1.35-fold) quintile after adjusting for confounders. We conclude that 3-MH, 3-MH/Crea and 3-MH/eGFR in plasma might be potential biomarkers to identify frail individuals or those at higher risk to be frail, and we assume that there might be biomarker thresholds to identify these individuals. However, further, especially longitudinal studies are needed

Mediterranean-type diet and brain structural change from 73 to 76 years in a Scottish cohort

STUDY FUNDING The data were collected by a Research into Ageing programme grant; research continues as part of the Age UK–funded Disconnected Mind project. The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross-council Lifelong Health and Wellbeing Initiative (MR/K026992/1), with funding from the BBSRC and Medical Research Council. Imaging and image analysis was performed at the Brain Research Imaging Centre (sbirc.ed.ac.uk/), Edinburgh, supported by the Scottish Funding Council SINAPSE Collaboration. Derivation of mean cortical thickness measures was funded by the Scottish Funding Council’s Postdoctoral and Early Career Researchers Exchange Fund awarded by SINAPSE to David Alexander Dickie. L.C.A.C. acknowledges funding from the Scottish Government's Rural and Environment Science and Analytical Services (RESAS) division.Peer reviewedPublisher PD

Dietary Patterns and Risk Factors of Frailty in Lebanese Older Adults

Factors associated with frailty, particularly dietary patterns, are not fully understood in Mediterranean countries. This study aimed to investigate the association of data-driven dietary patterns with frailty prevalence in older Lebanese adults. We conducted a cross-sectional national study that included 352 participants above 60 years of age. Sociodemographic and health-related data were collected. Food frequency questionnaires were used to elaborate dietary patterns via the K-mean cluster analysis method. Frailty that accounted for 15% of the sample was twice as much in women (20%) than men (10%). Identified dietary patterns included a Westernized-type dietary pattern (WDP), a high intake/Mediterranean-type dietary pattern (HI-MEDDP), and a moderate intake/Mediterranean-type dietary pattern (MOD-MEDDP). In the multivariate analysis, age, waist to height ratio, polypharmacy, age-related conditions, and WDP were independently associated with frailty. In comparison to MOD-MEDDP, and after adjusting for covariates, adopting a WDP was strongly associated with a higher frailty prevalence in men (OR = 6.63, 95% (CI) (1.82–24.21) and in women (OR = 11.54, 95% (CI) (2.02–65.85). In conclusion, MOD-MEDDP was associated with the least prevalence of frailty, and WDP had the strongest association with frailty in this sample. In the Mediterranean sample, a diet far from the traditional one appears as the key deleterious determinant of frailt

Nutrients

Few data are available regarding dietary habits of the elderly, especially about dairy products (DPs) (total DP and milk, fresh DP, and cheese), whereas these are part of healthy habits. The aim was to describe the socio-demographic characteristics, food, and nutritional intakes of elderly DP consumers. The sample consisted of 1584 participants from the Three-City-Bordeaux cohort (France), who answered a food frequency questionnaire and a 24-h dietary recall. Socio-demographic characteristics, practice of physical activity, Body Mass Index, and polymedication were registered. The sample was 76.2 years (SD 5.0 years) on average, 35% were in line with the French dietary guidelines for DP (3 or 4 servings of DP/day), while 49% were below, and 16% above. Women were significantly more likely to declare the highest total DP (≥4 times/day), milk (>1 time/day), and fresh DP (>1.5 times/day) frequency consumption. The highest cheese frequency consumers (>1.5 times/day) were more likely men, married, and ex-smokers. The highest frequency of fresh DP intake was significantly associated with the lowest energy and lipid intakes, and that of cheese with the highest consumption of charcuteries, meat, and alcohol. This cross-sectional analysis confirmed that the socio-demographics and dietary characteristics varied across DP sub-types consumed, which encourages individual consideration of these confounders in further analyses

Dairy Product Intake and Long-Term Risk for Frailty among French Elderly Community Dwellers

Dairy products (DP) are part of a food group that may contribute to the prevention of physical frailty. We aimed to investigate DP exposure, including total DP, milk, fresh DP and cheese, and their cross-sectional and prospective associations with physical frailty in community-dwelling older adults. The cross-sectional analysis was carried out on 1490 participants from the Three-City Bordeaux cohort. The 10-year frailty risk was examined in 823 initially non-frail participants. A food frequency questionnaire was used to assess DP exposure. Physical frailty was defined as the presence of at least 3 out of 5 criteria of the frailty phenotype: weight loss, exhaustion, slowness, weakness, and low physical activity. Among others, diet quality and protein intake were considered as confounders. The baseline mean age of participants was 74.1 y and 61% were females. Frailty prevalence and incidence were 4.2% and 18.2%, respectively. No significant associations were observed between consumption of total DP or DP sub-types and frailty prevalence or incidence (OR = 1.40, 95%CI 0.65–3.01 and OR = 1.75, 95%CI 0.42–1.32, for a total DP consumption >4 times/d, respectively). Despite the absence of beneficial associations of higher DP consumption on frailty, older adults are encouraged to follow the national recommendations regarding DP

Invest Ophthalmol Vis Sci

Purpose: We investigated the cross-sectional associations between macular pigment optical density (MPOD), plasma lutein (L), and zeaxanthin (Z) concentrations and cognitive function in 184 older adults of the 3-City-Bordeaux cohort. Methods: MPOD was measured using the two-wavelength autofluorescence method with a modified scanning laser ophthalmoscope. Plasma L and Z (L+Z) concentrations were determined by high-performance liquid chromatography and were considered either crude or expressed as a ratio of the concentration of plasma lipids (total cholesterol [TC] + triglycerides [TG]). Cognitive performances were assessed using the following four separate neuropsychological tests: the Mini-Mental State Examination (MMSE), the Isaacs Set Test (IST), the Benton Visual Retention Test (BVRT), and the sum of the three free recalls of the Free and Cued Selective Reminding Test (FCSRT). These test results were summarized by a composite global cognitive z-score. Results: Higher MPOD at 0.5 degrees was significantly associated with a higher composite z-score (beta = 0.15, 95% confidence interval [CI] 0.04-0.26), higher BVRT (beta = 0.39, 95%CI 0.08-0.70), and higher IST (beta = 1.16, 95%CI 0.11-2.22) performances. Higher plasma L+Z concentrations were significantly associated with higher IST scores (beta = 0.97, 95%CI 0.01-1.94). Furthermore, a higher L+Z/TC+TG ratio was associated with a higher composite z-score (beta = 0.12, 95%CI 0.01-0.23), along with higher IST (beta = 1.02, 95%CI 0.002-2.04) and FCSRT (beta = 1.55, 95%CI 0.41-2.69) performances. Conclusions: This analysis suggested that both higher MPOD and L+Z concentrations were significantly associated with higher cognitive performances. However, MPOD measurements have the advantage of being a fast and representative measure of long-term carotenoid intake

Ultra-processed foods: how functional is the NOVA system?

BACKGROUND: In the NOVA classification system, descriptive criteria are used to assign foods to one of four groups based on processing-related criteria. Although NOVA is widely used, its robustness and functionality remain largely unexplored. We determined whether this system leads to consistent food assignments by users. METHODS: French food and nutrition specialists completed an online survey in which they assigned foods to NOVA groups. The survey comprised two lists: one with 120 marketed food products with ingredient information and one with 111 generic food items without ingredient information. We quantified assignment consistency among evaluators using Fleiss' κ (range: 0-1, where 1 = 100% agreement). Hierarchical clustering on principal components identified clusters of foods with similar distributions of NOVA assignments. RESULTS: Fleiss' κ was 0.32 and 0.34 for the marketed foods (n = 159 evaluators) and generic foods (n = 177 evaluators), respectively. There were three clusters within the marketed foods: one contained 90 foods largely assigned to NOVA4 (91% of assignments), while the two others displayed greater assignment heterogeneity. There were four clusters within the generic foods: three clusters contained foods mostly assigned to a single NOVA group (69-79% of assignments), and the fourth cluster comprised 28 foods whose assignments were more evenly distributed across the four NOVA groups. CONCLUSIONS: Although assignments were more consistent for some foods than others, overall consistency among evaluators was low, even when ingredient information was available. These results suggest current NOVA criteria do not allow for robust and functional food assignments

Dietary Glycemic Load and Plasma Amyloid-β Biomarkers of Alzheimer's Disease

Previous studies have highlighted links between a high-glycemic-load (GL) diet and Alzheimer's disease in apolipoprotein E ε4 (APOE4) carriers. However, the impact of high-GL diet on plasma amyloid-β (Aβ), an Alzheimer's disease hallmark that can be detected decades before clinical symptomatology, is unknown. This study examined the association between plasma Aβ peptides (Aβ(40), Aβ(42) concentration and Aβ(42)/Aβ(40) ratio) and GL. The influence of the GL of four meal types (breakfast, lunch, afternoon snack, and dinner) was also determined. From the prospective Three-City study, 377 participants with plasma Aβ measurements, and who completed the Food Frequency Questionnaire, were selected. The association between plasma Aβ and GL was tested using an adjusted linear regression model. Lunch GL was associated with a lower plasma Aβ(42) concentration (β = -2.2 [CI = -4.27, -0.12], p = 0.038) and lower Aβ(42)/Aβ(40) ratio (β = -0.009 [CI = -0.0172, -0.0007], p = 0.034) in the model adjusted for center, age, sex, education level, APOE4 status, energy intake, serum creatinine, total cholesterol, and Mediterranean-like diet. No significant association was found with the GL of the other meal types. These results suggest that dietary GL may independently modulate the plasma Aβ of the APOE4 status. The mechanism underlying diet, metabolic response, and Aβ peptide regulation must be elucidated