Identifying the relation between food groups and biological ageing: a data-driven approach.

BACKGROUND: Heterogeneity in ageing rates drives the need for research into lifestyle secrets of successful agers. Biological age, predicted by epigenetic clocks, has been shown to be a more reliable measure of ageing than chronological age. Dietary habits are known to affect the ageing process. However, much remains to be learnt about specific dietary habits that may directly affect the biological process of ageing. OBJECTIVE: To identify food groups that are directly related to biological ageing, using Copula Graphical Models. METHODS: We performed a preregistered analysis of 3,990 postmenopausal women from the Women's Health Initiative, based in North America. Biological age acceleration was calculated by the epigenetic clock PhenoAge using whole-blood DNA methylation. Copula Graphical Modelling, a powerful data-driven exploratory tool, was used to examine relations between food groups and biological ageing whilst adjusting for an extensive amount of confounders. Two food group-age acceleration networks were established: one based on the MyPyramid food grouping system and another based on item-level food group data. RESULTS: Intake of eggs, organ meat, sausages, cheese, legumes, starchy vegetables, added sugar and lunch meat was associated with biological age acceleration, whereas intake of peaches/nectarines/plums, poultry, nuts, discretionary oil and solid fat was associated with decelerated ageing. CONCLUSION: We identified several associations between specific food groups and biological ageing. These findings pave the way for subsequent studies to ascertain causality and magnitude of these relationships, thereby improving the understanding of biological mechanisms underlying the interplay between food groups and biological ageing.

The Associations of Habitual Intake of Sulfur Amino Acids, Proteins and Diet Quality with Plasma Sulfur Amino Acid Concentrations: The Maastricht Study.

BACKGROUND: Plasma sulfur amino acids (SAAs), i.e., methionine, total cysteine (tCys), total homocysteine (tHcy), cystathionine, total glutathione (tGSH), and taurine, are potential risk factors for obesity and cardiometabolic disorders. However, except for plasma tHcy, little is known about how dietary intake modifies plasma SAA concentrations. OBJECTIVE: To investigate whether the intake of SAAs and proteins or diet quality is associated with plasma SAAs. METHODS: Data from a cross-sectional subset of The Maastricht Study (n = 1145, 50.5% men, 61 interquartile range: [55, 66] y, 22.5% with prediabetes and 34.3% with type 2 diabetes) were investigated. Dietary intake was assessed using a validated food frequency questionnaire. The intake of SAAs (total, methionine, and cysteine) and proteins (total, animal, and plant) was estimated from the Dutch and Danish food composition tables. Diet quality was assessed using the Dutch Healthy Diet Index, the Mediterranean Diet Score, and the Dietary Approaches to Stop Hypertension score. Fasting plasma SAAs were measured by liquid chromatography (LC) tandem mass spectrometry (MS) (LC/MS-MS). Associations were investigated with multiple linear regressions with tertiles of dietary intake measures (main exposures) and z-standardized plasma SAAs (outcomes). RESULTS: Intake of total SAAs and total proteins was positively associated with plasma tCys and cystathionine. Associations were stronger in women and in those with normal body weight. Higher intake of cysteine and plant proteins was associated with lower plasma tHcy and higher cystathionine. Higher methionine intake was associated with lower plasma tGSH, whereas cysteine intake was positively associated with tGSH. Higher intake of methionine and animal proteins was associated with higher plasma taurine. Better diet quality was consistently related to lower plasma tHcy concentrations, but it was not associated with the other SAAs. CONCLUSION: Targeted dietary modifications might be effective in modifying plasma concentrations of tCys, tHcy, and cystathionine, which have been associated with obesity and cardiometabolic disorders.

Protein intake and bone mineral density: Cross-sectional relationship and longitudinal effects in older adults.

BACKGROUND: There are several mechanisms via which increased protein intake might maintain or improve bone mineral density (BMD), but current evidence for an association or effect is inconclusive. The objectives of this study were to investigate the association between dietary protein intake (total, plant and animal) with BMD (spine and total body) and the effects of protein supplementation on BMD. METHODS: Individual data from four trials that included either (pre-)frail, undernourished or healthy older adults (aged ≥65 years) were combined. Dietary intake was assessed with food records (2, 3 or 7 days) and BMD with dual-energy X-ray absorptiometry (DXA). Associations and effects were assessed by adjusted linear mixed models. RESULTS: A total of 1570 participants [57% women, median (inter-quartile range): age 71 (68-75) years] for which at least total protein intake and total body BMD were known were included in cross-sectional analyses. In fully adjusted models, total protein intake was associated with higher total body and spine BMD [beta (95% confidence interval): 0.0011 (0.0006-0.0015) and 0.0015 (0.0007-0.0023) g/cm2 , respectively]. Animal protein intake was associated with higher total body and spine BMD as well [0.0011 (0.0007-0.0016) and 0.0017 (0.0010-0.0024) g/cm2 , respectively]. Plant protein intake was associated with a lower total body and spine BMD [-0.0010 (-0.0020 to -0.0001) and -0.0019 (-0.0034 to -0.0004) g/cm2 , respectively]. Associations were similar between sexes. Participants with a high ratio of animal to plant protein intake had higher BMD. In participants with an adequate calcium intake and sufficient serum 25(OH)D concentrations, the association between total protein intake with total body and spine BMD became stronger. Likewise, the association between animal protein intake with total body BMD was stronger. In the longitudinal analyses, 340 participants [58% women, median (inter-quartile range): age 75 (70-81) years] were included. Interventions of 12 or 24 weeks with protein supplementation or protein supplementation combined with resistance exercise did not lead to significant improvements in BMD. CONCLUSIONS: An association between total and animal protein intake with higher BMD was found. In contrast, plant protein intake was associated with lower BMD. Research is warranted to further investigate the added value of dietary protein alongside calcium and vitamin D for BMD improvement, especially in osteopenic or osteoporotic individuals. Moreover, more research on the impact of a plant-based diet on bone health is needed.

Perspective: Vegan Diets for Older Adults? A Perspective On the Potential Impact On Muscle Mass and Strength.

Consumers are increasingly encouraged to consume more plant-based foods and lower their consumption of foods from animal origin. Concurrently, older adults are recommended to consume an adequate amount of high-quality dietary protein for the prevention of age-related muscle loss. In the current Perspective article, we discuss why it may not be preferred to consume a vegan diet at an older age. Our perspective is based on the proposed lower bioavailability and functionality of proteins in a vegan diet due to the matrix of the whole-food protein sources, the lower essential amino acid (EAA) content, and specific EAA deficiencies in proteins derived from plant-based foods. We propose that a vegan diet increases the risk of an inadequate protein intake at an older age and that current strategies to improve the anabolic properties of plant-based foods are not feasible for many older adults. We provide recommendations for further research to substantiate the remaining knowledge gaps regarding the consequences of a vegan diet on skeletal muscle mass and strength at an older age.

Relative Validity and Reliability of Isometric Lower Extremity Strength Assessment in Older Adults by Using a Handheld Dynamometer.

BACKGROUND: Handheld dynamometry (HHD) is a practical alternative to traditional testing of lower extremity strength. However, its reliability and validity across different populations and settings are not clear. HYPOTHESIS: We hypothesize that HHD is a valid and reliable device to assess lower extremity strength in a population of older adults. STUDY DESIGN: Cross-sectional/cohort. LEVEL OF EVIDENCE: Level 3. METHODS: This study included 258 older adults (≥65 years). Isometric knee extension and flexion force were measured by 1 examiner, using an HHD (n = 222), including 3 repetitions to calculate within-day intrarater reliability. These measurements were repeated by the examiner in a subgroup (n = 23) to analyze intrarater reliability over a test-retest period of on average 8 weeks. In addition, HHD force measures were performed by a second examiner (n = 29) to analyze interrater reliability. In another subgroup (n = 77), isometric knee extension and flexion torque were measured by 1 examiner using both the HHD and Biodex System 4 to assess relative validity. RESULTS: HHD and Biodex measurements were highly correlated and showed excellent concurrent validity. HHD systematically overestimated torque as compared with Biodex by 8 N·m on average. Same-day intrarater intraclass correlation coefficients (ICCs) ranged from 0.97 to 0.98. Interrater reliability ICCs ranged from 0.83 to 0.95. CONCLUSION: HHD represents a reliable and valid alternative to Biodex to rank individuals on leg strength, or to assess within-person changes in leg strength over time, because of the high validity and reliability. The HHD is less suited for absolute strength assessment because of significant systematic overestimations. CLINICAL RELEVANCE: Clinicians are encouraged to use HHD to rank older adults on leg strength, or to assess within-person changes in leg strength over time, but not to compare readings with cut-offs or normative values.

Nutritional concerns later in life.

In an ageing society, the preservation of health and function is becoming increasingly important. The present paper acknowledges that ageing is malleable and focuses on diets and key nutritional concerns later in life. It presents evidence for the importance of healthful dietary patterns and points towards specific nutritional concerns later in life and conveys three main messages: (1) considering health maintenance and malnutrition risk, both dietary quality in terms of healthful dietary patterns and dietary quantity are important later in life, (2) ageing-related changes in nutrient physiology and metabolism contribute to the risk of inadequacies or deficiencies for specific nutrients, e.g. vitamin D, vitamin B12 and protein and (3) that current food-based dietary guidelines propagate a shift into the direction of Mediterranean type of diets including more plant-based foods. Limited scientific evidence on nutritional requirements of older adults, along with envisaged shifts towards diets rich in plant foods, are challenges that need to be addressed in order to develop tailored nutritional recommendations and dietary guidance for older adults.

A novel oral nutritional supplement improves gait speed and mitochondrial functioning compared to standard care in older adults with (or at risk of) undernutrition: results from a randomized controlled trial.

Undernutrition in older adults is mainly addressed by oral nutritional supplements, which do not affect physical functioning. In this study, we tested a novel oral nutritional supplement that included whey and casein protein, ursolic acid, free branch-chained amino acids and vitamin D against a standard supplement. We included older adults (>65y) with (or at risk of) undernutrition (n=82) and randomized them to 12 weeks of novel or standard supplement. Both groups showed significant increases in body mass. No within or between-group differences in lean body mass were observed. Fat mass increased significantly more in the standard than the novel supplement group (time*treatment effect P=0.045). The novel supplement group showed a larger improvement in walking performance on distances of 4m (treatment x time interaction P=0.048) and 400m (treatment x time interaction P=0.038) than the standard treatment group. Gene sets related to mitochondrial functioning and oxidative phosphorylation were upregulated in the novel supplement group and downregulated in the standard supplement group. We conclude that a 12-week intervention with the novel supplement improved walking performance both during short and long distance as compared to a standard supplement, which can largely be explained by increased mitochondrial functioning in the group receiving the novel supplement.

Vitamin B-6 intake is related to physical performance in European older adults: results of the New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe (NU-AGE) study.

BACKGROUND: Maintenance of high physical performance during aging might be supported by an adequate dietary intake of niacin, vitamins B-6 and B-12, and folate because these B vitamins are involved in multiple processes related to muscle functioning. However, not much is known about the association between dietary intake of these B vitamins and physical performance. OBJECTIVES: The objectives of this study were to investigate the association between dietary intake of niacin, vitamins B-6 and B-12, and folate and physical performance in older adults and to explore mediation by niacin status and homocysteine concentrations. METHODS: We used baseline data from the New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe (NU-AGE) trial, which included n = 1249 healthy older adults (aged 65-79 y) with complete data on dietary intake measured with 7-d food records and questionnaires on vitamin supplement use and physical performance measured with the short physical performance battery and handgrip dynamometry. Associations were assessed by adjusted linear mixed models. RESULTS: Intake of vitamin B-6 was related to lower chair rise test time [ß: -0.033 ± 0.016 s (log); P = 0.043]. Vitamin B-6 intake was also significantly associated with handgrip strength, but for this association, a significant interaction effect between vitamin B-6 intake and physical activity level was found. In participants with the lowest level of physical activity, higher intake of vitamin B-6 tended to be associated with greater handgrip strength (ß: 1.5 ± 0.8 kg; P = 0.051), whereas in participants in the highest quartile of physical activity, higher intake was associated with lower handgrip strength (ß: -1.4 ± 0.7 kg; P = 0.041). No evidence was found for an association between intake of niacin, vitamin B-12, or folate and physical performance or for mediation by niacin status or homocysteine concentrations. CONCLUSIONS: Vitamin B-6 intake was associated with better chair rise test time in a population of European healthy older adults and also with greater handgrip strength in participants with low physical activity only. Homocysteine concentrations did not mediate these associations. The NU-AGE trial was registered at clinicaltrials.gov as NCT01754012.

A 4-week exercise and protein program improves muscle mass and physical functioning in older adults - A pilot study.

BACKGROUND: Prehabilitation might attenuate common surgery-induced losses in muscle mass and physical performance. Beneficial effects of physical exercise with protein supplementation have been reported in older adults, but typically after an intervention of at least 12 weeks. The time-window for pre-surgery training is often limited to around 30 days, and it is not known if it is possible to achieve comparable results in such a short time window. OBJECTIVES: The aim of this study was to pilot-test the effectiveness of a controlled four-week combined exercise and protein supplementation program on skeletal muscle-related outcomes in a Dutch older adult population. DESIGN: This study was a one-armed pilot trial. PARTICIPANTS: Seventeen older men and women, aged 55-75y, not scheduled for surgery. INTERVENTION: A 4-week intervention program consisting of a twice-weekly supervised resistance and high-intensity aerobic exercise training of 75 min, combined with daily protein supplementation (2 doses of 15.5 g/day at breakfast and lunch). MEASUREMENT: After two and four weeks, isometric quadriceps maximal voluntary contraction (MVC) was assessed via Biodex and quadriceps cross-sectional area (CSA) via magnetic resonance imaging. Other outcome measures were handgrip strength, chair rise time and maximal aerobic capacity (VO2-max), as assessed from a submaximal exercise test. RESULTS: Compliance to the supervised training sessions (99.3%) and the protein supplementation (97%) was very high. The 4-week exercise and protein program led to an increase in quadriceps CSA of 2.3 ± 0.7 cm2 (P = 0.008) in the dominant leg and 3.2 ± 0.7 cm2 (P < 0.001) in the non-dominant leg. Isometric quadriceps MVC increased in the dominant leg (Δ14 ± 4 Nm, P = 0.001) and in the non-dominant leg (Δ17 ± 5 Nm, P = 0.003). Chair rise test time improved with -3.8 ± 0.5 s (P < 0.0001), and VO2-max improved with 3.3 ± 1.1 ml/min/kg (P = 0.014). We observed no changes in body weight and handgrip strength. CONCLUSION: A 4-week exercise and protein intervention led to improvements in muscle-related outcomes in older adults with low levels of physical activity.

Dietary Intakes of Vegetable Protein, Folate, and Vitamins B-6 and B-12 Are Partially Correlated with Physical Functioning of Dutch Older Adults Using Copula Graphical Models.

BACKGROUND: In nutritional epidemiology, dealing with confounding and complex internutrient relations are major challenges. An often-used approach is dietary pattern analyses, such as principal component analysis, to deal with internutrient correlations, and to more closely resemble the true way nutrients are consumed. However, despite these improvements, these approaches still require subjective decisions in the preselection of food groups. Moreover, they do not make efficient use of multivariate dietary data, because they detect only marginal associations. We propose the use of copula graphical models (CGMs) to model and make statistical inferences regarding complex associations among variables in multivariate data, where associations between all variables can be learned simultaneously. OBJECTIVE: We aimed to reconstruct nutritional intake and physical functioning networks in Dutch older adults by applying a CGM. METHODS: We addressed this issue by uncovering the pairwise associations between variables while correcting for the effect of remaining variables. More specifically, we used a CGM to infer the precision matrix, which contains all the conditional independence relations between nodes in the graph. The nonzero elements of the precision matrix indicate the presence of a direct association. We applied this method to reconstruct nutrient-physical functioning networks from the combined data of 4 studies (Nu-Age, ProMuscle, ProMO, and V-Fit, total n = 662, mean ± SD age = 75 ± 7 y). The method was implemented in the R package nutriNetwork which is freely available at https://cran.r-project.org/web/packages/nutriNetwork. RESULTS: Greater intakes of vegetable protein and vitamin B-6 were partially correlated with higher scores on the total Short Physical Performance Battery (SPPB) and the chair rise test. Greater intakes of vitamin B-12 and folate were partially correlated with higher scores on the chair rise test and the total SPPB, respectively. CONCLUSIONS: We determined that vegetable protein, vitamin B-6, folate, and vitamin B-12 intakes are partially correlated with improved functional outcome measurements in Dutch older adults.