Search

OBJECTIVES: To assess the impact of a personalized diet, with or without addition of VSL#3 preparation, on biomarkers of inflammation, nutrition, oxidative stress and intestinal microbiota in 62 healthy persons aged 65-85 years. DESIGN: Open label, randomized, multicenter study. PRIMARY ENDPOINT: High-sensitivity C-reactive protein. SETTING: Community. INTERVENTIONS: Eight week web-based dietary advice (RISTOMED platform) alone or with supplementation of VSL#3 (2 capsules per day). The RISTOMED diet was optimized to reduce inflammation and oxidative stress. MEASUREMENTS: Blood and stool samples were collected on days 1 and 56. RESULTS: Diet alone reduced ESR (p = 0.02), plasma levels of cholesterol (p < 0.01) and glucose (p = 0.03). Addition of VSL#3 reduced ESR (p = 0.05) and improved folate (p = 0.007), vitamin B12 (p = 0.001) and homocysteine (p < 0.001) plasma levels. Neither intervention demonstrated any further effects on inflammation. Subgroup analysis showed 40 participants without signs of low-grade inflammation (hsCRP

Background: Mediterranean diets limit red meat consumption and increase intakes of high-phytate foods, a combination that could reduce iron status. Conversely, higher intakes of fish, a good source of selenium, could increase selenium status. Objectives: A 1-y randomized controlled trial [New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe (NU-AGE)] was carried out in older Europeans to investigate the effects of consuming a Mediterraneanstyle diet on indices of inflammation and changes in nutritional status. Methods: Selenium and iron intakes and status biomarkers were measured at baseline and after 1 y in 1294 people aged 65–79 y from 5 European countries (France, Italy, the Netherlands, Poland, and the United Kingdom) who had been randomly allocated either to a Mediterranean-style diet or to remain on their habitual, Western diet. Results: Estimated selenium intakes increased significantly with the intervention group (P < 0.01), but were not accompanied by changes in serum selenium concentrations. Iron intakes also increased (P < 0.001), but there was no change in iron status. However, when stratified by study center, there were positive effects of the intervention on iron status for serum ferritin for participants in Italy (P = 0.04) and France (P = 0.04) and on soluble transferrin receptor (sTfR) for participants in Poland (P < 0.01). Meat intake decreased and fish intake increased to a greater degree in the intervention group, relative to the controls (P < 0.01 for both), but the overall effects of the intervention on meat and fish intakes were mainly driven by data from Poland and France. Changes in serum selenium in the intervention group were associated with greater changes in serum ferritin (P = 0.01) and body iron (P = 0.01), but not sTfR (P = 0.73); there were no study center × selenium status interactions for the iron biomarkers. Conclusions: Consuming a Mediterranean-style diet for 1 y had no overall effect on iron or selenium status, although there were positive effects on biomarkers of iron status in some countries. The NU-AGE trial was registered at clinicaltrials.gov as NCT01754012. Am J Clin Nutr 2019;00:1–12.

Objectives The aim of this work was to examine the cross-sectional relationship between body composition (BC) markers for adipose and lean tissue and bone mass, and a wide range of specific inflammatory and adipose-related markers in healthy elderly Europeans. Methods A whole-body dual-energy X-ray absorptiometry (DXA) scan was made in 1121 healthy (65–79 years) women and men from five European countries of the “New dietary strategies addressing the specific needs of elderly population for a healthy aging in Europe” project (NCT01754012) cohort to measure markers of adipose and lean tissue and bone mass. Pro-inflammatory (IL-6, IL-6Rα, TNF-α, TNF-R1, TNF-R2, pentraxin 3, CRP, alpha-1-acid glycoprotein, albumin) and anti-inflammatory (IL-10, TGF-β1) molecules as well as adipose-related markers such as leptin, adiponectin, ghrelin, and resistin were measured by magnetic bead-based multiplex-specific immunoassays and biochemical assays. Results BC characteristics were different in elderly women and men, and more favorable BC markers were associated with a better adipose-related inflammatory profile, with the exception of skeletal muscle mass index. No correlation was found with the body composition markers and circulating levels of some standard pro- and anti-inflammatory markers like IL-6, pentraxin 3, IL-10, TGF-β1, TNF-α, IL-6Rα, glycoprotein 130, TNF-α-R1, and TNF-α-R2. Conclusions The association between BC and inflammatory and adipose-related biomarkers is crucial in decoding aging and pathophysiological processes, such as sarcopenia. DXA can help in understanding how the measurement of fat and muscle is important, making the way from research to clinical practice. Key Points • Body composition markers concordantly associated positively or negatively with adipose-related and inflammatory markers, with the exception of skeletal muscle mass index. • No correlation was found with the body composition markers and circulating levels of some standard pro- and anti-inflammatory markers like IL-6, pentraxin 3, IL-10, TGF-β1, TNF-α, IL-6Rα, gp130, TNF-α-R1, and TNF-α-R2. • Skeletal muscle mass index (SMI) shows a good correlation with inflammatory profile in age-related sarcopenia. Electronic supplementary material The online version of this article (10.1007/s00330-018-5973-2) contains supplementary material, which is available to authorized users.

The gut microbiota (GM) is a complex, evolutionarily molded ecological system, which contributes to a variety of physiological functions. The GM is highly dynamic, being sensitive to environmental stimuli, and its composition changes over the host’s entire lifespan. However, the basic question of how much these changes may be ascribed to variables such as population, diet, genetics and gender, and/or to the aging process per se is still largely unanswered. We argue that comparison among studies on centenarians—the best model of healthy aging and longevity—recruited from different geographical areas/populations (different genetics and dietary habits) can help to disentangle the contribution of aging and non-aging-related variables to GM remodeling with age. The current review focuses on the role of population, gender and host genetics as possible drivers of GM modification along the human aging process. The feedback impact of age-associated GM variation on the GM–brain axis and GM metabolomics is also discussed. We likewise address the role of GM in neurodegenerative diseases such as Parkinson’s and Alzheimer’s, and its possible therapeutic use, taking advantage of the fact that centenarians are characterized by an extreme (healthy) phenotype versus patients suffering from age-related pathologies. Finally, it is argued that longitudinal studies combining metagenomics sequencing and in-depth phylogenetic analysis with a comprehensive phenotypic characterization of centenarians and patients using up-to-date omics (metabolomics, transcriptomics and meta-transcriptomics) are urgently needed.

The intake of adequate amounts and types of nutrients is key for sustaining health and a good quality of life, particularly in the elderly population. There is considerable evidence suggesting that physiological changes related to age and sex modify nutritional needs, and this may be related to age-associated changes in body composition (BC), specifically in lean and fat body mass. However, there is a clear lack of understanding about the association of nutrients in blood and BC parameters in the elderly. This study investigated the relationships among blood nutrients (amino acids, fatty acids, major elements, trace-elements, and vitamins), BC and nutrient intake in a population of 176 healthy male and female Italian adults between the ages of 65 and 79 years. 89 blood markers, 77 BC parameters and dietary intake were evaluated. Multivariate data analysis was applied to infer relationships between datasets. As expected, the major variability between BC and the blood nutrient profile (BNP) observed was related to sex. Aside from clear sex-specific differences in BC, female subjects had higher BNP levels of copper, copper-to-zinc ratio, phosphorous and holotranscobalamin II and lower concentrations of branched-chain amino acids (BCAAs) and proline. Fat mass, percentage of fat mass, percentage of lean mass and the skeletal muscle index (SMI) correlated the most with BNP in both sexes. Our data showed positive correlations in male subjects among ethanolamine, glycine, albumin, and sulfur with SMI, while palmitoleic acid and oleic acid exhibited negative correlations. This differed in female subjects, where SMI was positively associated with albumin, folic acid and sulfur, while CRP, proline and cis-8,11,14-eicosatrienoic acid were negatively correlated. We investigated the influence of diet on the observed BNP and BC correlations. Intriguingly, most of the components of the BNP, except for folate, did not exhibit a correlation with nutrient intake data. An understanding of the physiological and biochemical processes underpinning the observed sex-specific correlations between BNP and BC could help in identifying nutritional strategies to manage BC-changes in aging. This would contribute to a deeper understanding of aging-associated nutritional needs with the aim of helping the elderly population to maintain metabolic health.

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.

Background: Nutrition-related knowledge (NRK) and nutrition-related attitudes (NRAs) are necessary for dietary changes toward healthier dietary patterns. In turn, healthier dietary patterns can be beneficial in maintaining health of older adults. Therefore, the aim of this cross-sectional study was to investigate whether NRK and NRAs were associated with lifestyle and health features among older adults (65+ years) from five European countries (France, Italy, Poland, the Netherlands and United Kingdom). Methods: Within the European project NU-AGE, 1,144 healthy elderly volunteers (65–79 years) were randomly assigned to two groups: intervention (NU-AGE diet) or control. After 1-year of follow-up, both NRK and NRAs were assessed during exit interviews, in combination with a number of lifestyle and health variables (e.g., physical activity, smoking, alcohol use, BMI, self-assessed health status). Multivariable linear regression models were used in data analysis. Results: In the NU-AGE study sample, good NRK was associated with lower BMI and higher physical activity. More positive NRAs were related to lower BMI and self-reported very good or good appetite. Moreover, both NRK and NRAs were associated with some socio-economic determinants, like financial situation, age, education, living area (for NRK), and country (for NRAs). Participants in the intervention group showed a better NRK (β = 0.367 [95% CI: 0.117; 0.617], p = 0.004) and more positive NRAs (β = 0.838 [95% CI: 0.318; 1.358], p = 0.002) than those in the control group. Higher self-evaluated knowledge was also significantly related to more positive NRAs (p < 0.001). The most popular sources of nutrition information were food labels, books and magazines on health, the dietitian and the doctor's office, although their importance varied significantly among countries, and, to a lesser extent, between women and men and between intervention and control group. Conclusion: Higher NRK and NRA scores were associated with lower BMI and higher physical activity level. Therefore, a good nutrition-related knowledge and positive nutrition-related attitudes can strongly and positively influence the health status and quality of life among the older population. These results offer a great opportunity for policy makers to implement educational programs in order to counteract the epidemic of obesity and to improve the health span of European population.

Background: The Mediterranean Diet has been proposed as an effective strategy to reduce inflammaging, a chronic low grade inflammatory status, and thus, to slow down the aging process. We evaluated whether a Mediterranean-like dietary pattern specifically targeting dietary recommendations of people aged over 65 years (NU-AGE diet) could be effective to shift dietary intake of older adults towards a healthful diet. Methods: Adults aged 65&ndash, 80 years across five EU-centers were randomly assigned to a NU-AGE diet group or control group. The diet group followed one year of NU-AGE dietary intervention specifying consumption of 15 food groups plus the use of a vitamin D supplement. Participants in the diet group received counselling and individually tailored dietary advice, food products and a vitamin D supplement. Dietary intake was assessed by means of seven-day food records at baseline and one-year follow-up. A continuous NU-AGE index (0&ndash, 160 points) was developed to assess NU-AGE diet adherence. Results: In total 1296 participants were randomized and 1141 participants completed the intervention (571 intervention, 570 control). After one year, the diet group improved mean intake of 13 out of 16 NU-AGE dietary components (p &lt, 0.05), with a significant increase in total NU-AGE index (difference in mean change = 21.3 &plusmn, 15.9 points, p &lt, 0.01). Conclusions: The NU-AGE dietary intervention, based on dietary recommendations for older adults, consisting of individual dietary counselling, free healthy foods and a vitamin D supplement, may be a feasible strategy to improve dietary intake in an aging European population.

Inflammaging is a recent theory of aging originally proposed in 2000 where data and conceptualizations regarding the aging of the immune system (immunosenescence) and the evolution of immune responses from invertebrates to mammals converged. This theory has received an increasing number of citations and experimental confirmations. Here we present an updated version of inflammaging focused on omics data – particularly on glycomics – collected on centenarians, semi-supercentenarians and their offspring. Accordingly, we arrived to the following conclusions: i) inflammaging has a structure where specific combinations of pro- and anti-inflammatory mediators are involved; ii) inflammaging is systemic and more complex than we previously thought, as many organs, tissues and cell types participate in producing pro- and anti-inflammatory stimuli defined “molecular garbage”; iii) inflammaging is dynamic, can be propagated locally to neighboring cells and systemically from organ to organ by circulating products and microvesicles, and amplified by chronic age-related diseases constituting a “local fire”, which in turn produces additional inflammatory stimuli and molecular garbage; iv) an integrated Systems Medicine approach is urgently needed to let emerge a robust and highly informative set/combination of omics markers able to better grasp the complex molecular core of inflammaging in elderly and centenarians.

The study of the extreme limits of human lifespan may allow a better understanding of how human beings can escape, delay, or survive the most frequent age-related causes of morbidity, a peculiarity shown by long-living individuals. Longevity is a complex trait in which genetics, environment, and stochasticity concur to determine the chance to reach 100 or more years of age [1]. Because of its impact on human metabolism and immunology, the gut microbiome has been proposed as a possible determinant of healthy aging [2, 3]. Indeed, the preservation of host-microbes homeostasis can counteract inflammaging [4], intestinal permeability [5], and decline in bone and cognitive health [6, 7]. Aiming at deepening our knowledge on the relationship between the gut microbiota and a long-living host, we provide for the first time the phylogenetic microbiota analysis of semi-supercentenarians, i.e.,105-109 years old, in comparison to adults, elderly,and centenarians, thus reconstructing the longest available human microbiota trajectory along aging. We highlighted the presence of a core microbiota ofhighly occurring, symbiotic bacterial taxa (mostly belonging to the dominant Ruminococcaceae, Lachnospiraceae, and Bacteroidaceae families), with a cumulative abundance decreasing along withage. Aging is characterized by an increasing abundance of subdominant species, as well as a rearrangementintheir co-occurrence network. These features are maintained in longevity and extreme longevity, but peculiarities emerged, especially in semi-supercentenarians, describing changes that, even accommodating opportunistic and allochthonous bacteria, might possibly supporthealth maintenance during aging, such as an enrichment and/or higher prevalence of health-associated groups (e.g., Akkermansia, Bifidobacterium, and Christensenellaceae).

Data showing a remarkable gender difference in life expectancy and mortality, including survival to extreme age, are reviewed starting from clinical and demographic data and stressing the importance of a comprehensive historical perspective and a gene–environment/lifestyle interaction. Gender difference regarding prevalence and incidence of the most important age-related diseases, such as cardiovascular and neurodegenerative diseases, cancer, Type 2 diabetes, disability, autoimmunity and infections, are reviewed and updated with particular attention to the role of the immune system and immunosenescence. On the whole, gender differences appear to be pervasive and still poorly considered and investigated despite their biomedical relevance. The basic biological mechanisms responsible for gender differences in aging and longevity are quite complex and still poorly understood. The present review focuses on centenarians and their offspring as a model of healthy aging and summarizes available knowledge on three basic biological phenomena, i.e. age-related X chromosome inactivation skewing, gut microbiome changes and maternally inherited mitochondrial DNA genetic variants. In conclusion, an appropriate gender-specific medicine approach is urgently needed and should be systematically pursued in studies on healthy aging, longevity and age-related diseases, in a globalized world characterized by great gender differences which have a high impact on health and diseases.

Individuals capable of reaching the extreme limit of human life such as centenarians are characterized by an exceptionally healthy phenotype—that is, a low number of diseases, low blood pressure, optimal metabolic and endocrine parameters, and increased diversity in the gut microbiota—and they are epigenetically younger than their chronological age. We present data suggesting that such a remarkable phenotype is largely similar to that found in adults following a calorie-restricted diet. Interviews with centenarians and historical data on the nutritional and lifestyle habits of Italians during the twentieth century suggest that as children and into adulthood, centenarians lived in an environment that was nonobesogenic, but at the same time the environment did not produce malnutrition. Centenarians appear to be creatures of habit, and we argue that their habit of eating meals at the same time each day favored the maintenance of circadian rhythms, including their sleep cycle. Finally, we argue that centenarians’ chronic inflammatory status, which we dubbed inflammaging, is peculiar, likely adaptive, and less detrimental than in younger people.

The pro- or anti-inflammatory activities of immunoglobulins G (IgGs) are controlled by the structure of the glycan N-linked to Asn297 of their heavy chain. The age-associated low grade inflammation (inflammaging) is associated with increased plasmatic levels of agalactosylated IgGs terminating with N-acetylglucosamine (IgG-G0) whose biogenesis has not been fully explained. Although the biosynthesis of glycans is in general mediated by glycosyltransferases associated with internal cell membranes, the extracellular glycosylation of circulating glycoproteins mediated by plasmatic glycosyltransferases has been recently demonstrated. In this study we have investigated the relationship between plasmatic glycosyltransferases, IgG glycosylation and inflammatory and aging markers. In cohorts of individuals ranging from infancy to centenarians we determined the activity of plasmatic β4 galactosyltransferase(s) (B4GALTs) and of α2,6-sialyltransferase ST6GAL1, the glycosylation of IgG, the GlycoAge test (a glycosylation-based marker of aging) and the plasma level of inflammatory and liver damage markers. Our results show that: 1) plasmatic B4GALTs activity is a new marker of aging, showing a linear increase throughout the whole age range. 2) plasmatic ST6GAL1 was high only in children and in people above 80, showing a quadratic relationship with age. 3) Neither plasmatic glycosyltransferase correlated with markers of liver damage. 4) plasmatic ST6GAL1 showed a positive association with acute phase proteins in offspring of short lived parents, but not in centenarians or in their offspring. 5) Although the glycosylation of IgGs was not correlated with the level of the two plasmatic glycosyltransferases, it showed progressive age-associated changes consistent with a shift toward a pro-inflammatory glycotype.

Within the scenario of an increasing life expectancy worldwide it is mandatory to identify determinants of healthy aging. Centenarian offspring (CO) is one of the most informative model to identify trajectories of healthy aging and their determinants (genetic and environmental), being representative of elderly in their 70th whose lifestyle can be still modified to attain a better health. This study is the first comprehensive investigation of the health status of 267 CO (mean age: 70.2 years) and adopts the innovative approach of comparing CO with 107 age‐matched offspring of non‐long‐lived parents (hereafter indicated as NCO controls), recruited according to strict inclusion demographic criteria of Italian population. We adopted a multidimensional approach which integrates functional and cognitive assessment together with epidemiological and clinical data, including pro‐ and anti‐inflammatory cytokines and adipokines, lipid profile, and insulin resistance. CO have a lower prevalence of stroke, cerebral thrombosis‐hemorrhage, hypertension, hypercholesterolemia, and other minor diseases, lower BMI and waist circumference, a better functional and cognitive status and lower plasma level of FT4 compared to NCO controls. We conclude that a multidimensional approach is a reliable strategy to identify the health status of elderly at an age when interventions to modify their health trajectory are feasible.