Aging is considered the major risk factor for cancer, one of the most important mortality causes in the western world. Inflammaging, a state of chronic, low-level systemic inflammation, is a ...pervasive feature of human aging. Chronic inflammation increases cancer risk and affects all cancer stages, triggering the initial genetic mutation or epigenetic mechanism, promoting cancer initiation, progression and metastatic diffusion. Thus, inflammaging is a strong candidate to connect age and cancer. A corollary of this hypothesis is that interventions aiming to decrease inflammaging should protect against cancer, as well as most/all age-related diseases. Epidemiological data are concordant in suggesting that the Mediterranean Diet (MD) decreases the risk of a variety of cancers but the underpinning mechanism(s) is (are) still unclear. Here we review data indicating that the MD (as a whole diet or single bioactive nutrients typical of the MD) modulates multiple interconnected processes involved in carcinogenesis and inflammatory response such as free radical production, NF-κB activation and expression of inflammatory mediators, and the eicosanoids pathway. Particular attention is devoted to the capability of MD to affect the balance between pro- and anti-inflammaging as well as to emerging topics such as maintenance of gut microbiota (GM) homeostasis and epigenetic modulation of oncogenesis through specific microRNAs.
Findings from animal and epidemiological research support the potential neuroprotective benefits from healthy diets. However, to establish diet-neuroprotective causal relations, evidence from dietary ...intervention studies is needed. NU-AGE is the first multicenter intervention assessing whether a diet targeting health in aging can counteract the age-related physiological changes in different organs, including the brain. In this study, we specifically investigated the effects of NU-AGE's dietary intervention on age-related cognitive decline.
NU-AGE randomized trial (NCT01754012, clinicaltrials.gov) included 1279 relatively healthy older-adults, aged 65-79 years, from five European centers. Participants were randomly allocated into two groups: "control" (
= 638), following a habitual diet; and, "intervention" (
= 641), given individually tailored dietary advice (NU-AGE diet). Adherence to the NU-AGE diet was measured over follow-up, and categorized into tertiles (low, moderate, high). Cognitive function was ascertained at baseline and at 1-year follow-up with the Consortium to Establish a Registry for Alzheimer's Disease (CERAD)-Neuropsychological Battery and five additional domain-specific single cognitive tests. The raw scores from the CERAD subtests excluding the Mini-Mental State Examination (MMSE) and the single tests were standardized into
-scores. Global cognition (measured with MMSE and CERAD-total score), and five cognitive domains (perceptual speed, executive function, episodic memory, verbal abilities, and constructional praxis) were created. Cognitive changes as a function of the intervention were analyzed with multivariable mixed-effects models.
After the 1-year follow-up, 571 (89.1%) controls and 573 (89.8%) from the intervention group participated in the post-intervention assessment. Both control and intervention groups showed improvements in global cognition and in all cognitive domains after 1 year, but differences in cognitive changes between the two groups were not statistically significant. However, participants with higher adherence to the NU-AGE diet showed statistically significant improvements in global cognition β 0.20 (95%CI 0.004, 0.39),
-value = 0.046 and episodic memory β 0.15 (95%CI 0.02, 0.28),
-value = 0.025 after 1 year, compared to those adults with lower adherence.
High adherence to the culturally adapted, individually tailored, NU-AGE diet could slow down age-related cognitive decline, helping to prevent cognitive impairment and dementia.
Aging is a dynamic process depending on intrinsic and extrinsic factors and its evolution is a continuum of transitions, involving multifaceted processes at multiple levels. It is recognized that ...frailty and sarcopenia are shared by the major age-related diseases thus contributing to elderly morbidity and mortality. Pre-frailty is still not well understood but it has been associated with global imbalance in several physiological systems, including inflammation, and in nutrition. Due to the complex phenotypes and underlying pathophysiology, the need for robust and multidimensional biomarkers is essential to move toward more personalized care. The objective of the present study was to better characterize the complexity of pre-frailty phenotype using untargeted metabolomics, in order to identify specific biomarkers, and study their stability over time. The approach was based on the NU-AGE project (clinicaltrials.gov, NCT01754012) that regrouped 1,250 free-living elderly people (65-79 y.o., men and women), free of major diseases, recruited within five European centers. Half of the volunteers were randomly assigned to an intervention group (1-year Mediterranean type diet). Presence of frailty was assessed by the criteria proposed by Fried et al. (2001). In this study, a sub-cohort consisting in 212 subjects (pre-frail and non-frail) from the Italian and Polish centers were selected for untargeted serum metabolomics at T0 (baseline) and T1 (follow-up). Univariate statistical analyses were performed to identify discriminant metabolites regarding pre-frailty status. Predictive models were then built using linear logistic regression and ROC curve analyses were used to evaluate multivariate models. Metabolomics enabled to discriminate sub-phenotypes of pre-frailty both at the gender level and depending on the pre-frailty progression and reversibility. The best resulting models included four different metabolites for each gender. They showed very good prediction capacity with AUCs of 0.93 (95% CI = 0.87-1) and 0.94 (95% CI = 0.87-1) for men and women, respectively. Additionally, early and/or predictive markers of pre-frailty were identified for both genders and the gender specific models showed also good performance (three metabolites; AUC = 0.82; 95% CI = 0.72-0.93) for men and very good for women (three metabolites; AUC = 0.92; 95% CI = 0.86-0.99). These results open the door, through multivariate strategies, to a possibility of monitoring the disease progression over time at a very early stage.
•Inflammaging is critical for ageing and age-related chronic diseases.•NU-AGE targets the Mediterranean whole diet as a major modulator of inflammaging.•NU-AGE consortium includes research centres, ...SMEs and food industries and federations.•NU-AGE will identify molecular targets responsible for the effect of NU-AGE diet.•NU-AGE will design industrially driven fortified foods for elderly.
The development of a chronic, low grade, inflammatory status named “inflammaging” is a major characteristic of ageing, which plays a critical role in the pathogenesis of age-related diseases. Inflammaging is both local and systemic, and a variety of organs and systems contribute inflammatory stimuli that accumulate lifelong. The NU-AGE rationale is that a one year Mediterranean whole diet (considered by UNESCO a heritage of humanity), newly designed to meet the nutritional needs of the elderly, will reduce inflammaging in fully characterized subjects aged 65–79 years of age, and will have systemic beneficial effects on health status (physical and cognitive). Before and after the dietary intervention a comprehensive set of analyses, including omics (transcriptomics, epigenetics, metabolomics and metagenomics) will be performed to identify the underpinning molecular mechanisms. NU-AGE will set up a comprehensive database as a tool for a systems biology approach to inflammaging and nutrition. NU-AGE is highly interdisciplinary, includes leading research centres in Europe on nutrition and ageing, and is complemented by EU multinational food industries and SMEs, interested in the production of functional and enriched/advanced traditional food tailored for the elderly market, and European Federations targeting policy makers and major stakeholders, from consumers to EU Food & Drink Industries.
Abstract Background Since preterm birth is associated with a constellation of pre-, peri- and post-natal risk factors, we hypothesised that prematurity may continue to impact the development of ...linguistic abilities even up to the end of the preschool years and beyond, giving rise to an atypical developmental trajectory. The study tested this hypothesis at six years of age, investigating whether language is affected by preterm birth and how different linguistic abilities are interrelated. Method Seventy monolingual Italian preterms and 34 age-matched controls were recruited. Linguistic abilities (vocabulary, grammar, and phonological awareness) as well as general cognitive developmental levels were measured. Results No general cognitive delay emerged, but less developed abilities in vocabulary, grammar, and phonological awareness were found in preterms compared to fullterms. Moreover, the relations among the different linguistic competences differed across groups. Conclusions Our study shows that even without brain damage, preterm birth continues to affect linguistic development up to the end of the preschool years, and probably beyond, highlighting a continuity between pre- and peri-natal life and subsequent development, and pointing to an atypical developmental trajectory in this population compared to fullterms (different rates of development, different strategies employed, and differences in the relationships among linguistic abilities).
A state of chronic, subclinical inflammation known as inflammaging is present in elderly people and represents a risk factor for all age-related diseases. Dietary supplementation with
fortified foods ...seems an appealing strategy to counteract inflammaging. The purpose of this study was to test the efficacy of elderly-tailored fortified milk on inflammaging and different health parameters.
A double-blind randomized cross-over study was performed on forty-eight volunteers aged 63-80 years. The fortified milk was enriched with ω-3 polyunsaturated fatty acids (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA), vitamins (25-hydroxyvitamin D, E, C, B6, B9, B12), and trace elements (zinc, selenium). The two intervention periods lasted for 12 weeks, with a 16-week washout intermission.
Compared to placebo, the consumption of fortified milk increased the circulating levels of different micronutrients, including vitamins and the ω-3 index of erythrocyte membranes. Conversely, it reduced the amount of arachidonic acid, homocysteine, and ω-6/ω-3 ratio.
Twelve-week daily consumption of
fortified milk has an overall positive impact on different health parameters related to inflammaging in the elderly.
Aging is a multifactorial process characterized by the accumulation of proteins undergoing oxidative modifications, either due to enhanced levels of oxidative stress or due to their decreased ...clearance; both facts are related to the establishment of chronic inflammatory processes. These processes are directly associated with functional and structural modifications of a key cellular component, namely the proteasome. In this study, levels of oxidized proteins, along with proteasome and immunoproteasome composition and activity on a selected group of 120 elderly volunteers were analyzed before and after the administration of a specific dietary protocol, based on an elderly tailored Mediterranean diet (the "NU-AGE diet"). A significant negative correlation between levels of oxidized/carbonylated proteins and proteasome function was confirmed, both before and after intervention. Furthermore, it was demonstrated that subgroups of non-frail subjects and women receive a greater benefit after the intervention, concerning specifically the proteasome content and activity. These data highlight the putative beneficial effects of Mediterranean diet on the major cellular proteolytic mechanism, the proteasome, in elderly people.
The aims of this study were to investigate whether specific linguistic difficulties in preterm children persist at eight years and to examine the interrelationships between language and literacy in ...this population, compared with a control group of full-term children. Sixty-eight monolingual Italian preterms and 26 chronologically matched controls were recruited. Language (grammar comprehension, lexical production and phonological awareness), literacy (reading comprehension, reading and writing) and general cognitive development were investigated. Results showed no general delay in preterms, but slight difficulties in specific linguistic abilities (grammar, lexicon, phoneme synthesis and deletion of the first syllable), more difficulties in literacy (speed in reading and accuracy in writing) and certain correlations among competencies turning out to be different from the control group. In conclusion, our study established that a partially atypical trajectory emerged in preterms, showing specific long-term effects of preterm birth on language and literacy development.
Abstract
Mitochondrial stress elicits the production of stress response molecules indicated as mitokines, including fibroblast growth factor 21 (FGF21), growth differentiation factor 15 (GDF15), and ...humanin (HN). Many diseases are characterized by progressive mitochondrial dysfunction with alterations of mitokine secretion. It is still controversial whether healthy aging and extreme longevity are accompanied by an altered production of mitokines. We analyzed FGF21, HN, and GDF15 plasma levels in 693 subjects aged from 21 to 113 years, and the association of these mitokines with parameters of health status. FGF21, HN, and GDF15 resulted increased in old age, with the highest levels found in centenarians. These molecules are associated with worsened parameters (such as handgrip strength, insulin sensitivity, triglycerides), particularly in 70-year-old persons, and their levels are inversely correlated with survival in the oldest subjects. Considering the positive biological effect of these molecules, our results can be interpreted in the framework of the hormetic paradigm as an attempt of the cells/tissues to cope with a stress that can have beneficial or detrimental effects depending on its intensity. Finally, persons with Down Syndrome (characterized by accelerated aging) have higher levels of GDF15 and HN with respect to their siblings, suggesting that these molecules, especially GDF15, could be considered markers of biological age.
Abstract
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.
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