The aim of this work was to conduct a systematic review of human studies on metabolite/lipid biomarkers of metabolic syndrome (MetS) and its components, and provide recommendations for future ...studies. The search was performed in MEDLINE, EMBASE, EMB Review, CINHAL Complete, PubMed, and on grey literature, for population studies identifying MetS biomarkers from metabolomics/lipidomics. Extracted data included population, design, number of subjects, sex/gender, clinical characteristics and main outcome. Data were collected regarding biological samples, analytical methods, and statistics. Metabolites were compiled by biochemical families including listings of their significant modulations. Finally, results from the different studies were compared. The search yielded 31 eligible studies (2005-2019). A first category of articles identified prevalent and incident MetS biomarkers using mainly targeted metabolomics. Even though the population characteristics were quite homogeneous, results were difficult to compare in terms of modulated metabolites because of the lack of methodological standardization. A second category, focusing on MetS components, allowed comparing more than 300 metabolites, mainly associated with the glycemic component. Finally, this review included also publications studying type 2 diabetes as a whole set of metabolic risks, raising the interest of reporting metabolomics/lipidomics signatures to reflect the metabolic phenotypic spectrum in systems approaches.
Studies have shown that an even protein intake distribution across meals increased 24-h muscle protein synthesis in young adults compared with a skewed intake. Whether this short-term result ...translates into long-term preservation of lean mass (LM) in older adults remains unknown.
The aim was to examine the extent to which protein quantity and distribution are associated with LM and appendicular LM (aLM), and their 2-y decline, in community-dwelling older adults.
Baseline and 2-y follow-up data from 351 men and 361 women (aged 67-84 y) in the NuAge study (Quebec Longitudinal Study on Nutrition as a Determinant of Successful Aging) with available body-composition data (by dual-energy X-ray absorptiometry) were used. Food intake was assessed with the use of three 24-h food recalls collected at baseline and 3 collected at the 2-y follow-up. Protein distribution across meals was calculated as the CV of protein ingested per meal, with lower values reflecting evenness of protein intake. Linear mixed-model analysis was performed to examine changes in LM and aLM across time, by sex, as conditioned by the quantity and distribution of protein intake, adjusted for potential covariates.
Over 2 y, LM declined in both men (-2.5% ± 4.0%) and women (-2.0% ± 3.4%) (P < 0.05), whereas aLM loss was not significant (men: -1.5% ± 4.8%; women: -1.2% ± 5.3%; P > 0.05). The decline in LM was not independently affected by the quantity and distribution of protein intake. Yet men and women with evenly distributed protein intakes and men with high protein intakes showed higher LM or aLM throughout the entire follow-up period, even after potential confounders were controlled for (P < 0.05).
Our results suggest that greater protein intakes and a more even distribution across meals are modifiable factors associated with higher muscle mass in older adults but not with losses over 2 y. Interventional studies should determine longer-term effects on preserving LM with aging.
Background
Motoric cognitive risk syndrome (MCR) is a pre-dementia stage. The existence of stable and transient MCR, their related clinical characteristics and their association with incident ...dementia is a matter of debate.
Objective
This study aims to examine the clinical characteristics and the time course associated with new onset, transient and stable MCR, and their association with incidence of probable dementia in community-dwelling older adults living in the province of Quebec (Canada).
Design
Quebec elderly population-based observational cohort study with 3 years of follow-up.
Setting
Community dwellers.
Subjects
A subset of participants (
n
= 1,113) from the “
Quebec Longitudinal Study on Nutrition and Successful Aging
” (NuAge) cohort.
Methods
Participants with MCR were identified at baseline and after 1 year of follow-up. Socio-demographic characteristics, 30-item Geriatric depression scale (GDS) score, cardiovascular risk factors and diseases were recorded at baseline. Incidence of probable dementia was measured at annual follow-up visits over a 3-year period.
Results
Over the period of the first year of follow-up, the prevalence of MCR was 8.5% with 4.3% having new onset MCR, 2.8% transient MCR and 1.4% stable MCR. A higher 30-item GDS score was reported with new onset and transient MCR, and the highest prevalence of cerebrovascular diseases was shown with stable MCR compared to non-MCR participants (
p
< 0.05). MCR was associated with overall incidence of probable dementia, regardless of its status (Hazard Ratio ≥ 1.86,
p
≤ 0.034).
Conclusion
Greater prevalence of depressive symptoms and cerebrovascular diseases were reported, respectively, with new onset and transient MCR, and stable MCR. The association of MCR with incidence of probable dementia remains significant, regardless of MCR subtypes.
Aging is associated with a progressive decline in muscle mass and strength, a process known as sarcopenia. Evidence indicates that mitochondrial dysfunction plays a causal role in sarcopenia and ...suggests that alterations in mitochondrial dynamics/morphology may represent an underlying mechanism. Caloric restriction (CR) is among the most efficient nonpharmacological interventions to attenuate sarcopenia in rodents and is thought to exert its beneficial effects by improving mitochondrial function. However, CR effects on mitochondrial morphology and dynamics, especially in aging muscle, remain unknown. To address this issue, we investigated mitochondrial morphology and dynamics in the oxidative soleus (SOL) and glycolytic white gastrocnemius (WG) muscles of adult (9-month-old)
-fed (AL; A-AL), old (22-month-old) AL-fed (O-AL), and old CR (O-CR) rats. We show that CR attenuates the aging-related decline in the muscle-to-body-weight ratio, a sarcopenic index. CR also prevented the effects of aging on muscle fiber type composition in both muscles. With aging, the SOL displayed fragmented SubSarcolemmal (SS) and InterMyoFibrillar (IMF) mitochondria, an effect attenuated by CR. Aged WG displayed enlarged SS and more complex/branched IMF mitochondria. CR had marginal anti-aging effects on WG mitochondrial morphology. In the SOL, DRP1 (pro-fission protein) content was higher in O-AL vs YA-AL, and Mfn2 (pro-fusion) content was higher in O-CR vs A-AL. In the gastrocnemius, Mfn2, Drp1, and Fis1 (pro-fission) contents were higher in O-AL vs A-AL. CR reduced this aging-related increase in Mfn2 and Fis1 content. Overall, these results reveal for the first time that aging differentially impacts mitochondrial morphology and dynamics in different muscle fiber types, by increasing fission/fragmentation in oxidative fibers while enhancing mitochondrial size and branching in glycolytic fibers. Our results also indicate that although CR partially attenuates aging-related changes in mitochondrial dynamics in glycolytic fibers, its anti-aging effect on mitochondrial morphology is restricted to oxidative fibers.
The increasing levels of bone marrow fat evident in aging and osteoporosis are associated with low bone mass and attributed to reduced osteoblastogenesis. Local lipotoxicity has been proposed as the ...primary mechanism driving this reduction in bone formation. However, no studies have examined the correlation between high levels of marrow fat volumes and changes in local cellularity. In this study, we hypothesize that areas of bone marrow with high fat volumes are associated with significant changes in cell number within a similar region of interest (ROI). Inbred albino Louvain (LOU) rats, originating from the Wistar strain, have been described as a model of healthy aging with the absence of obesity but expressing the typical features of age-related bone loss. We compared local changes in distal femur cellularity and structure in specific ROI of undecalcified bone sections from 4- and 20-month-old male and female LOU rats and Wistar controls. Our results confirmed that older LOU rats exhibited significantly higher fat volumes than Wistar rats (
p
< 0.001). These higher fat volume/total volume were associated with lower trabecular number (
p
< 0.05) and thickness (
p
< 0.05) and higher trabecular separation (
p
< 0.05). In addition, osteoblast and osteocyte numbers were reduced in the similar ROI containing high levels of adiposity, while osteoclast number was higher compared to control (
p
< 0.03). In summary, marrow ROIs with a high level of adiposity were associated with a lower bone mass and changes in cellularity explaining associated bone loss. Further studies assessing the levels of lipotoxicity in areas of high local marrow adiposity and identifying molecular actors involved in this phenomenon are still required.
Depression is common and medically relevant illness that has been associated to a state of “accelerated aging” and can significantly compromise successful aging. In recent years, the concept of ...“brain reserve” has emerged to describe some individuals having an increased “baseline adaptive neuroplasticity”, providing greater dynamic capacity for adjusting and remodeling cortical circuits to various stressors. We hypothesize that brain reserve may have neuroprotective effects against late life depression. Here, we discuss the modulatory capacity of stress and corticosteroid hormones on hippocampal plasticity and neuronal viability in late life depression as well as the anti-depressive of ketamine and scopolamine mediated by stimulation of the mammalian target of rapamycin, increased inhibitory phosphorylation of GSK-3β, and increased synaptogenesis. This review shall shed light on complex neurobiological mechanisms that underpin late life depression and help to better understand neural correlates of resilience. Investigating how rat models of increased cognitive reserve mitigate a chronic mild stress-elicited depression will afford new insights in the search for new therapeutic targets to treat this neuropsychiatric disorder.
Background
Lower protein intake in older adults is associated with loss of muscle mass and strength. The present study aimed to provide a pooled estimate of the overall prevalence of protein intake ...below recommended (according to different cut‐off values) among community‐dwelling older adults, both within the general older population and within specific subgroups.
Methods
As part of the PRevention Of Malnutrition In Senior Subjects in the EU (PROMISS) project, a meta‐analysis was performed using data from four cohorts (from the Netherlands, UK, Canada, and USA) and four national surveys from the Netherlands, Finland (two), and Italy. Within those studies, data on protein and energy intake of community‐dwelling men and women aged ≥55 years were obtained by either a food frequency questionnaire, 24 h recalls administered on 2 or 3 days, or food diaries administered on 3 days. Protein intake below recommended was based on the recommended dietary allowance of 0.8 g/kg body weight (BW)/d, by using adjusted BW (aBW) instead of actual BW. Cut‐off values of 1.0 and 1.2 were applied in additional analyses. Prevalences were also examined for subgroups according to sex, age, body mass index (BMI), education level, appetite, living status, and recent weight loss.
Results
The study sample comprised 8107 older persons. Mean ± standard deviation protein intake ranged from 64.3 ± 22.3 (UK) to 80.6 ± 23.7 g/d the Netherlands (cohort) or from 0.94 ± 0.38 (USA) to 1.17z ± 0.30 g/kg aBW/d (Italy) when related to BW. The overall pooled prevalence of protein intake below recommended was 21.5% (95% confidence interval: 14.0–30.1), 46.7% (38.3–55.3), and 70.8% (65.1–76.3) using the 0.8, 1.0, and 1.2 cut‐off value, respectively. A higher prevalence was observed among women, individuals with higher BMI, and individuals with poor appetite. The prevalence differed only marginally by age, education level, living status, and recent weight loss.
Conclusions
In community‐dwelling older adults, the prevalence of protein intake below the current recommendation of 0.8 g/kg aBW/d is substantial (14–30%) and increases to 65–76% according to a cut‐off value of 1.2 g/kg aBW/d. To what extent the protein intakes are below the requirements of these older people warrants further investigation.
Abstract
Background
Older adults are underrepresented in research. Heterogeneity of research processes in this population, specifically in long-term care (LTC) and geriatric acute care (GAC), is not ...well described and may impede the design, planning, and conduct of research. In this study, we identified, quantified, and mapped stakeholders, research stages, and transversal themes of research processes, to develop a mapping framework to improve research capacity by better characterizing this heterogeneity.
Methods
Multicomponent mixed methods study. An environmental scan was used to initiate a preliminary framework. We conducted a systematic literature search on processes, barriers, and methods for clinical research in GAC and LTC to extract and update stakeholders, research stages, and themes. Importance and interactions of elements were synthesized via heatmaps by number of articles, mentions, and content intersections.
Results
For our initial framework and environmental scan, we surveyed 24 stakeholders. Of 9277 records, 68 articles were included in our systematic review and allowed us to identify 12 stakeholders, 13 research stages, 17 transversal themes (either barriers, facilitators, general themes, or recommendations), and 1868 intersections. Differences in relative importance between LTC and GAC emerged for stakeholders (staff, managers vs. caregivers, ethics committees), and for research stages (funding, facility recruitment vs. ethics, individual recruitment). Crucial themes according to specific stakeholders were collaboration for the research team; communication, trust, and human resources for managers; heterogeneity for patients and residents. A heatmap framework synthesizing vital stakeholders and themes per research stage was generated.
Conclusions
We identified and quantified the interactions between stakeholders, stages, and themes to characterize heterogeneity in LTC and GAC research. Our framework may serve as a blueprint to co-construct and improve each stage of the research process.
Little is known about how normal variation in dietary patterns in humans affects the ageing process. To date, most analyses of the problem have used a unidimensional paradigm, being concerned with ...the effects of a single nutrient on a single outcome. Perhaps then, our ability to understand the problem has been complicated by the fact that both nutrition and the physiology of ageing are highly complex and multidimensional, involving a high number of functional interactions. Here we apply the multidimensional geometric framework for nutrition to data on biological ageing from 1560 older adults followed over four years to assess on a large-scale how nutrient intake associates with the ageing process. Ageing and age-related loss of homeostasis (physiological dysregulation) were quantified via the integration of blood biomarkers. The effects of diet were modelled using the geometric framework for nutrition, applied to macronutrients and 19 micronutrients/nutrient subclasses. We observed four broad patterns: (1) The optimal level of nutrient intake was dependent on the ageing metric used. Elevated protein intake improved/depressed some ageing parameters, whereas elevated carbohydrate levels improved/depressed others; (2) There were non-linearities where intermediate levels of nutrients performed well for many outcomes (i.e. arguing against a simple more/less is better perspective); (3) There is broad tolerance for nutrient intake patterns that don't deviate too much from norms ('homeostatic plateaus'). (4) Optimal levels of one nutrient often depend on levels of another (e.g. vitamin E and vitamin C). Simpler linear/univariate analytical approaches are insufficient to capture such associations. We present an interactive tool to explore the results in the high-dimensional nutritional space. Using multidimensional modelling techniques to test the effects of nutrient intake on physiological dysregulation in an aged population, we identified key patterns of specific nutrients associated with minimal biological ageing. Our approach presents a roadmap for future studies to explore the full complexity of the nutrition-ageing landscape.
Weight loss is prevalent in the elderly population, with deleterious health consequences, notably loss of lean body mass and subsequent functional decline. Protein intake below the current RDA 0.8 ...g/(kg · d) is also common in older adults; however, the link between the 2 has received little attention. Our objective was to assess the relation between protein intake and incident 1-y weight loss ≥5% in community-dwelling older adults. We conducted a nested, prospective, case-control study in 1793 community-living elderly participants of the Quebec Longitudinal Study of Nutrition as a Determinant of Successful Aging (NuAge). We studied 211 incident cases of 1-y weight loss (≥5%) and 211 weight-stable controls (±2%) matched by sex and age category (70 ± 2, 75 ± 2, and 80 ± 2 y). Diet was measured by 3 nonconsecutive 24-h recalls. ORs (95% CIs) for the association between protein intake and weight loss were computed by using conditional logistic regression. After adjustment for body mass index, energy intake, appetite, smoking status, physical activity level, physical function, chronic diseases and medications, depressive symptoms, and serum albumin and ultrasensitive C-reactive protein, the ORs of weight loss in participants with low protein intakes <0.8 g/(kg · d) were 2.56 (95% CI: 1.01, 6.50) compared with participants with very high protein intakes ≥1.2 g/(kg · d). Corresponding numbers were 2.15 (95% CI: 1.02, 4.56) in participants with moderate protein intakes 0.8-<1.0 g/(kg · d) and 1.33 (95% CI: 0.77, 2.28) in participants with high protein intakes 1.0-1.2 g/(kg · d). Our results suggest that protein intakes >1.0 g/(kg · d) are protective against weight loss in healthy older adults. These findings add epidemiologic evidence in support of higher optimal protein intakes than the current guidelines for healthy older adults.
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