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Background and purpose: Younger recipients of total hip arthroplasty (THA) highly prioritize returning to preoperative levels of physical activity (PA). Surgeons have tended to give cautious advice concerning high-impact sports participation, but there have been few long-term studies. The purpose of our study was to investigate the risk of revision arthroplasty in relation to postoperative PA levels. Methods: Patients registered in the Geneva Arthroplasty Register (GAR) who had elective THA when they were aged < 65 years were studied. Postoperative PA was collected prospectively 5-yearly using the UCLA activity scale. Cox proportional hazards models were used to estimate associations between PA and risk of revision THA. Results: Amongst 1,370 eligible subjects, median age at THA 58 years (interquartile range 51–61), UCLA scores were available for 973 (71%). During follow-up over 15 years, there were 79 revisions, giving a cumulative risk of 7.4% (95% confidence interval [CI] 5.8–9.4). After adjusting for covariates, we found an increased risk of revision for each unit increase in postoperative PA (HR 1.2, CI 1.1–1.4), and among people performing the most intensive PA (HR 2.7, CI 1.3–5.6) compared with those who were inactive. Conclusion: The overall risk of revision was small but intensive and moderate PA may be associated with an increased risk of revision.

Introduction With demographic changes, there is increasing demand for individuals and governments to lengthen working lives. Jobs that are very physically demanding are likely to be more difficult to sustain at older ages. If workers at risk of mismatch of demand and capability could be identified early, there would be opportunities for intervention for health or lifestyle and/or re-training or redeployment.Objective To investigate whether self-reported walking speed (a good measure of function in elderly people) predicted health-related job loss (HRJL) longitudinally over 5 years of follow-up among middle-aged workers.Design Data came from the Health and Employment After Fifty (HEAF) prospective cohort study of middle-aged people (aged 50–64 years) in UK.Setting General population survey (sampling frame was 24 General Practice registers).Participants The cohort included 8134 people recruited in 2013–2014. For the current analyses, 5217 people who ever worked and completed at least one follow-up questionnaire were eligible.Primary outcome Exit from employment mainly or partly for health reasons (HRJL).Results At baseline, very slow walking speed was associated with: obesity, physical inactivity, smoking (men), financial hardship, lower educational attainment and not being in professional occupations. In total, 527 people (10%) reported at least one HRJL during follow-up. After adjustment, the HR for HRJL among men with very slow walking-speed was 4.32, 95% CI 2.72 to 6.87 and among women was 4.47, 95% CI 3.04 to 6.57. After further adjustment for ‘difficulty coping with physical demands at work’, hazards remained doubled in men and women.Conclusions Self-reported walking speed could help identify older workers who are at increased risk of HRJL. This could provide opportunities for intervention through optimising health and lifestyle, restricting physical workload, retraining or redeployment. Early appropriate intervention could enable longer working lives and promote healthier, more equal ageing.

Abstract Background Governments of Western countries need people to work to older ages, however the COVID-19 pandemic impacted the workforce by pushing older adults to retire. Socio-demographic factors that influence the decision to retire in the pre-pandemic period were, poor or good health, finances, marital status, and gender. The aim of this study was to explore aspects that contributed to the decision to retire among middle-aged and older people in England who retired during the COVID-19 pandemic. Methods In September 2022 semi-structured interviews were conducted with a sample of participants from the Health and Employment After Fifty (HEAF) study who retired since March 2020. Consenting participants were purposively selected to achieve a wide spread of characteristics deemed important in the retirement process. Telephone interviews were conducted, audio-recorded, transcribed and then thematically analysed. Results 24 interviews were conducted (10 men and 14 women, mean age 65 years). Six themes were identified: four of them were non-COVID-19 aspects while two can be interpreted as impact of COVID-19 on the workforce. Work-related factors were of major importance. A sense of appreciation and attachment in relation to their employer, and conversely high work demands and stress, as well as changes in work responsibilities and work practices since lockdown and/or perception of personal safety in the workplace during the pandemic influenced their retirement decision, as did physical and mental health issues. Another theme suggested that some participants felt they had reached the ‘right’ age and needed to spend more time with family. Having the financial capacity to retire was widely mentioned but was never the main factor. Conclusions The decision to retire during the pandemic was multi-factorial although changes to work during lockdown were of great importance. Post-pandemic, our findings suggest that there are modifiable aspects of work, including appreciation and fair pay and work conditions, that employers and policy makers could encourage to retain their older workers.

IntroductionMale reproduction is under the control of the hypothalamus–pituitary–gonadal (HPG) axis. The endocannabinoid system (ECS) and the kisspeptin system (KS) are two major signaling systems in the central and peripheral control of reproduction, but their possible interaction has been poorly investigated in mammals. This manuscript analyzes their possible reciprocal modulation in the control of the HPG axis.Materials and methodsAdolescent male rats were treated with kisspeptin-10 (Kp10) and endocannabinoid anandamide (AEA), the latter alone or in combination with the type 1 cannabinoid receptor (CB1) antagonist rimonabant (SR141716A). The hypothalamic KS system and GnRH expression, circulating sex steroids and kisspeptin (Kiss1) levels, and intratesticular KS and ECS were evaluated by immunohistochemical and molecular methods. Non-coding RNAs (i.e., miR145-5p, miR-132-3p, let7a-5p, let7b-5p) were also considered.ResultsCirculating hormonal values were not significantly affected by Kp10 or AEA; in the hypothalamus, Kp10 significantly increased GnRH mRNA and aromatase Cyp19, Kiss1, and Kiss1 receptor (Kiss1R) proteins. By contrast, AEA treatment affected the hypothalamic KS at the protein levels, with opposite effects on the ligand and receptor, and SR141716A was capable of attenuating the AEA effects. Among the considered non-coding RNA, only the expression of miR145-5p was positively affected by AEA but not by Kp10 treatment. Localization of Kiss1+/Kiss1R+ neurons in the arcuate nucleus revealed an increase of Kiss1R-expressing neurons in Kp10- and AEA-treated animals associated with enlargement of the lateral ventricles in Kp10-treated animals. In the brain and testis, the selected non-coding RNA was differently modulated by Kp10 or AEA. Lastly, in the testis, AEA treatment affected the KS at the protein levels, whereas Kp10 affected the intragonadal levels of CB1 and FAAH, the main modulator of the AEA tone. Changes in pubertal transition-related miRNAs and the intratesticular distribution of Kiss1, Kiss1R, CB1, and CB2 following KP and AEA treatment corroborate the KS-ECS crosstalk also showing that the CB1 receptor is involved in this interplay.ConclusionFor the first time in mammals, we report the modulation of the KS in both the hypothalamus and testis by AEA and revealed the KP-dependent modulation of CB1 and FAAH in the testis. KP involvement in the progression of spermatogenesis is also suggested.

Background: Alzheimer’s disease (AD) and Parkinson’s disease (PD) are multifactorial neurodegenerative disorders that are mostly treated with drugs inhibiting key enzymes of cholinergic and aminergic neurotransmission, such as acetyl and butyryl cholinesterase (AChE, BuChE) or monoamine oxidases (MAO)-A/B, and of Aβ 1–40 aggregation. Diet plant components with multitarget functions are promising compounds in the prevention of AD and PD. Our aim was to identify neuroprotective compounds from Annurca apple polyphenol extract (AFPE). Methods: AFPE was fractionated by gel filtration, and the eluted peaks were subjected to chemical analyses (i.e., RP-HPLC and mass spectrometry), determination of inhibitory enzyme activity and cell effects by MTT, and morphology assays. Results: In AFPE, we identified thaumatin-like protein 1a, belonging to the pathogenesis-related protein (PR) family. This protein showed the best inhibitory activity on AChE, MAO-A (IC50 = 5.53 µM and 1.71 µM, respectively), and Aβ1–40 fibril aggregation (IC50 = 9.16 µM), compared to AFPE and other polyphenol-containing fractions. Among the latter, Peak 4 reverted Aβ fibril formation (IC50 = 104.87 µM). Moreover, thaumatin-like protein 1a protected AGS and MKN-28 cells from serum-deprivation-induced stress conditions. Conclusions: We showed that AFPE exerted neuroprotective functions not only through its polyphenols but also through thaumatin-like protein 1a, which acted like a multitarget molecule.

Abstract Background The COVID-19 pandemic markedly disrupted people’s lives. It caused higher mortality and morbidity amongst individuals from poorer socio-economic position (SEP). It is well-recognised that job loss has a negative impact on health. We hypothesised that health effects of the pandemic on middle-aged people might be different depending on SEP and changes in employment. Methods Data are from the Health and Employment After Fifty (HEAF), a cohort recruited 2013–2014 when aged 50–64 through 24 English general practices. At baseline and annually since, participants completed a questionnaire reporting about demographics, employment, health, lifestyle, and finances. In 2021 we sent an e-survey to all contactable HEAF participants, asking about effects of the first lockdown (March-July 2020). Outcomes were participants’ perception of worsening of mental, physical health, and self-rated health (SRH) since lockdown. Associations between SEP, COVID-19 related employment changes and health were explored with Poisson regression with robust standard error, with adjustment for age, sex, and pre-pandemic SRH. Results In total, 2,469 (53%) returned a usable questionnaire, amongst whom 2,344 provided complete information for these analyses (44% men, mean age 65.7 years). Worsening of mental, physical or SRH since lockdown was reported by 21%, 27% and 17% respectively. Mutually adjusted models showed that reporting struggling financially pre-pandemic (versus living comfortably) was associated with an increased risk of deterioration in: mental (RR = 2.0, 95%CI 1.7–2.5), physical health (RR = 2.0, 95%CI 1.6–2.3), and SRH (RR = 1.6, 95%CI 1.2–2.1). Participants working from home during lockdown and those who lost their job (as opposed to those with unchanged employment) were at increased risk of reporting deterioration in mental health and SRH. Conclusion In a cohort of older workers, working from home, job loss and poorer pre-pandemic SEP were all associated with worsening of mental health and SRH since lockdown.

The ends of human chromosomes are defended by DNA–protein complexes named telomeres, which inhibit the chromosomes from fusing with each other and from being known as a double-strand break by DNA reparation proteins. Telomere length is a marker of biological aging, and disfunction of telomeres is related to age-related syndromes. Telomere attrition has been shown to be accelerated by oxidative stress and inflammation. Telomere length has been proven to be positively linked with nutritional status in human and animal scientific research as several nutrients influence it through mechanisms that imitate their function in cellular roles including oxidative stress and inflammation. Data reported in this article support the idea that following a low-in-fat and rich-plant polyphenols food diet seems to be able to slow down the shortening of telomeres.

Health promotion requires good nutrition and an adequate lifestyle, which together contribute to people’s well-being [...]

ABSTRACT In the Maternal Vitamin D Osteoporosis Study (MAVIDOS) randomized trial, vitamin D supplementation in pregnancy did not lead to greater neonatal bone mass across the trial as a whole, but, in a prespecified secondary analysis by season of birth, led to greater neonatal bone mass among winter‐born babies. Demonstrating persistence of this effect into childhood would increase confidence in a long‐term benefit of this intervention. We investigated whether antenatal vitamin D supplementation increases offspring bone mineralization in early childhood in a prespecified, single‐center follow‐up of a double‐blinded, multicenter, randomized controlled clinical trial based in the UK (MAVIDOS). A total of 1123 women in early pregnancy with a baseline 25‐hydroxyvitamin D level 25–100 nmol/L from three research centers (2008–2014) were randomized to 1000 IU/d cholecalciferol or matched placebo from 14 weeks of gestation to delivery. Offspring born at the Southampton, UK research center were assessed at age 4 years (2013–2018). Anthropometry and dual‐energy X‐ray absorptiometry (DXA) were performed (yielding whole body less head [WBLH] bone mineral content [BMC], areal bone mineral density [aBMD], bone area [BA], and body composition). Of 723 children, 564 (78.0%) children attended the 4‐year visit, 452 of whom had a useable DXA. Maternal vitamin D supplementation led to greater WBLH aBMD in the children compared with placebo (mean [95% confidence interval {CI}]: supplemented group: 0.477 (95% CI, 0.472–0.481) g/cm2; placebo group: 0.470 (95% CI, 0.466–0.475) g/cm2, p = 0.048). Associations were consistent for BMC and lean mass, and in age‐ and sex‐adjusted models. Effects were observed across the whole cohort irrespective of season of birth. Maternal‐child interactions were observed, with a greater effect size among children with low milk intake and low levels of physical activity. Child weight, height, and body mass index (BMI) were similar by maternal randomization group. These findings suggest a sustained beneficial effect of maternal vitamin D supplementation in pregnancy on offspring aBMD at age 4 years, but will require replication in other trials. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

BackgroundPhysical activity, nutrition and other lifestyle factors play important roles in maintaining musculoskeletal health. The coronavirus disease (COVID-19) originated in late 2019, spread globally to be declared a pandemic by the World Health Organisation in March 2020, and led to widespread behaviour change. The aim of this study was to use two existing cohorts, the Hertfordshire Cohort Study (HCS) and Health and Employment After Fifty Study (HEAF), to understand how wave one of the COVID-19 pandemic impacted lifestyle factors associated with musculoskeletal health in the UK.Methods125 eligible participants, 65 males and 60 females (drawn from the HCS study, median (IQR) age 84.3 (82.4-86.6) years, all Caucasian, and community dwelling) were contacted by telephone and asked to complete a questionnaire administered by a trained researcher. Data collection occurred over the period July 2020 to February 2021. 2469 participants, 1086 men and 1383 women (drawn from the HEAF study, median age 65.7 (62.0-69.3) years, mostly Caucasian and community dwelling) completed an online questionnaire in March 2021.ResultsIn HCS, 47% respondents reported being less physically active than before the pandemic (and only 5% more so), 27% said they consumed less alcohol compared to pre-pandemic times (and only 3% more so), and 18% reported eating less than before, although quality of diet was generally unchanged over this timeframe surveyed. In HEAF, 44% participants said they were less active than before the pandemic, while 17% reported being more active. The majority of participants reported no changes in alcohol consumption and diet; however, 19% said they drank more than before (32% of which was above recommended levels), 16% said their diet was less healthy, and 19% reported eating more than before.ConclusionWe have reported the experience of the first wave of the COVID-19 pandemic among participants of two Caucasian community dwelling UK cohorts, highlighting the impact of the pandemic on lifestyle factors associated with musculoskeletal health. Changed physical activity levels were reported in a high proportion of respondents in both studies; an investigation of reversibility of these changes is required.

Abstract Background Loneliness is an important public health issue associated with mortality and morbidity. Often researched amongst older people, less is known about risk factors for loneliness among adults aged 50–64 years who are in work. We investigated (a) if exit from the workforce increases the odds of loneliness; (b) whether adverse psychosocial work factors are associated with increased odds of loneliness over 2 years of follow-up; and (c) whether the association is stronger among subjects still working compared with those who have exited the workforce. Methods Data came from the Health and Employment After Fifty (HEAF) study, a large population cohort who provided questionnaire information about work and health at baseline and 2 annual follow-ups. Logistic regression was used to explore the association between psychosocial risk factors and loneliness at follow-up 2, with adjustment for loneliness at baseline, sex, age, self-rated health, living alone, and mental health diagnosis. Results Of the initial 8134 participants, 4521 were working at baseline and provided data for this analysis. Of those, 507 (11.2%) were defined as lonely at 2 years’ follow-up. Exiting the workforce was not significantly associated with loneliness (OR = 1.1, 95%CI: 0.7–1.7). However, negative psychosocial work factors predicted loneliness at follow-up. After mutual adjustment, lack of choice at work (OR: 1.5, 95%CI: 1.1–1.9), often lying awake worrying about work (OR: 1.4, 95%CI: 1.0–1.9) and perceived not coping with physical demands of the job (OR: 1.3, 95%CI: 1.0–1.7) were independent predictors, with associations robust to adjustment for demographic factors and health. Associations were only slightly altered when we restricted the sample to those who remained in work until the end of follow-up. Conclusions Loneliness amongst middle-aged working adults is not predicted by permanent work exit but is predicted by individuals’ perceptions about their work. Provision of good-quality work, matched to the capacity of the older worker, could prevent loneliness.

The aim of this study was to investigate the influence of body composition on the anaerobic strength of the lower extremities, as well as the prediction of body composition on the results of anaerobic ability in professional football players. Materials and Method. The sample of respondents consists of female football players who compete in the highest rank of the competition, the Serbian Super League. The total number of respondents included in the study was 21 female football players (age 19.38 ± 3.69, body height 166.48 ± 6.17 cm, body weight 59.98 ± 7.09 kg). The study is of a transversal nature and testing was done in the pre-competition period. The sample of measuring instruments used in the research are body composition and assessment of anaerobic strength of the lower extremities. Assessment of body composition was performed indoors using a multifrequency bioelectric impedance (Inbody 770). Variables for estimating the anaerobic strength of the lower extremities were obtained using a bicycle ergometer (Monark 839E) in the Wingate Anaerobic Test. Results. The results of body composition show a statistically significant influence on the prediction of maximum anaerobic strength of the lower extremities in professional female football players (p < 0.05), as well as on the overall work in the anaerobic zone and the mean values ​​of anaerobic strength. Regression analysis of the influence of body composition on the parameters of maximum strength in (W/kg) and fatigue rate does not show statistically significant results. Conclusion. There is a statistically significant influence of body composition, such as: body weight, lean body mass (%), muscle mass in absolute and relative values, on the values ​​of maximum anaerobic strength, mean values ​​of anaerobic strength and overall work in professional female footballers.

Abstract Background Axial spondyloarthritis (axSpA) frequently presents during working age and therefore impacts work participation. Biologic therapies have demonstrated a positive impact on work-related outcomes in clinical trials but real world data are limited. Therefore, we investigated the prevalence and predictors of work impairment and disability among axSpA patients attending a biologic therapy clinic. Methods This was a single-centre, cross-sectional study of patients with axSpA treated with biologic therapy. Work participation was assessed with the Work Productivity and Activity Impairment (WPAI) Questionnaire. Work outcomes (presenteeism, absenteeism, health-related job loss) were compared for gender, time since diagnosis, smoking status and disease outcome measures. Results Data were available for 165 patients (mean age 47.6 years, 75% male, 21% current smokers). Mean time since diagnosis was 15.5 years and mean duration of biologic therapy 4.7 years; 19/165 (11.5%) were on a tapered-dose regimen. Occupational data were available for 144 patients amongst whom 101 (70.1%) were either currently employed or in full time education. Of those eligible to work, 17/118 (14.4%) reported inability to work due to their axSpA. Amongst those in employment, 10.8% reported absenteeism due to axSpA in the week prior to their clinic visit (mean hours missed = 13). The mean work productivity impairment was 23%. Higher disease activity (BASDAI) and markers of global health, quality of life and pain, (BAS-G, ASQoL and spinal pain VAS) were associated with axSpA related job loss, absenteeism and presenteeism. Conclusions In this group of axSpA patients on biologic therapy (mean age 47.6 years), almost 1 in 6 (14.4%) reported axSpA related job loss. Poor work outcomes: axSpA-related work disability, absenteeism and presenteeism were associated with poorer scores for patient-reported disease outcome measures. Strategies for enhancing work productivity should be directed towards those patients at risk of poor work outcomes. More data are needed including details of the types of work that are most difficult with axSpA.

The introduction of alien fish species in wetland ecosystems could have a great impact on freshwater communities and ecological processes. Despite fish introduction has been noticed as one of the principal cause of freshwater extinctions, ecosystem processes alteration, and change in aquatic community assemblage, very few data about impact on freshwater reptiles are available. As study model we used two neighbour sub-populations of the endangered Sicilian pond turtle, Emys trinacris, inhabiting two small, close each other and very similar lakes, except for the presence of allocthonous fish, Cyprinus carpio and Gambusia hoolbroki in one of the two. The multi-year study allowed highlighting significant differences in abundance, growth and reproductive output between the two freshwater turtle sub-populations, suggesting their influence on phenotypic plasticity of the studied population. These results are discussed in the light of previous evidence about the impact of these alien species on abundance and assemblage of the invertebrate community with an evident impact on niche width, diet composition and therefore energy intake by Emys trinacris. These data may provide important information to address management strategies and conservation actions of small wetland areas inhabited by pond turtles, pointing out a threats never highlighted up to now.

Identifying coastal tracts suitable for sea turtle reproduction is crucial for sea turtle conservation in a context of fast coastal development and climate change. In contrast to nesting aggregations, diffuse nesting is elusive and assessing nesting levels is challenging. A total of 323 nesting events by the loggerhead sea turtle Caretta caretta have been reported in Sicily, the largest Mediterranean island, in the 1944–2021 period, mostly in the last decade. Specific monitoring efforts are the most likely explanation for such an increase and shows that sea turtle nesting may be underestimated or completely ignored in many areas with scattered nesting. The real nesting level along the 464 km sandy shores of Sicily is still unknown and more research is needed. The observed incubation period was relatively long (57 d) suggesting that a majority of males are produced in Sicily, in contrast to the typical female-biased sex ratio of sea turtles. In a context of climate warming producing sex ratios more skewed towards females, the potential of Sicily as a male-producing area should be further investigated. Other reproductive parameters are provided, such as clutch size and hatching and emergence success. A negative effect of relocation on the latter two was observed.

IntroductionRapidly increasing population old age dependency ratios create a growing economic imperative for people to work to older ages. However, rates of older worker employment are only increasing slowly. Amongst a cohort of contemporary older workers, we investigated risk factors for health-related job loss (HRJL) over 2 years of follow-up.MethodsHEAF is a population based cohort study of adults in England (aged 50-64 years at baseline) who provided information about socio-demographic characteristics, lifestyle, and work at baseline and annual follow-ups. Exits from paid work were mapped and risk factors for HRJL explored in a multiple-record survival dataset by Cox proportional hazards models.Results2475 (75%) men and 2668 (66%) women were employed; 115 (4.6%) men and 182 (6.8%) women reported HRJL. Employment as road transport drivers/in vehicle trades (men), or as teaching/education/nursing/midwifery professionals or in caring personal services (women), was more frequent among people exiting work for health-related versus non-health-related reasons. Principal socio-demographic and lifestyle risk factors for HRJL were: struggling financially (men and women); low physical activity (men); being overweight or obese, and current smoking (women). Mutually adjusted work-related risk factors for HRJL were job dissatisfaction, and not coping with the physical (hazard ratio [95% confidence interval]: men 5.34[3.40,8.39]; women 3.73[2.48,5.60]) or mental demands (women only, 2.02[1.38,2.96]) of work.ConclusionsEmployment characteristics of contemporary older workers differ by sex. Job satisfaction and perceived ability to cope with the physical and mental demands of work are key determinants of HRJL which employers could potentially influence to enable work to older ages.

The first record of the red swamp crayfish in Sicily dates back to 2003 and, since then, the species seemed to be confined to a few localities in western Sicily. A small “citizen science” project carried out from November 2016 onwards led to the creation of the “Sicilian Procambarus working group” (SPwg), which aims at monitoring the distribution and impact of the species in Sicily. To date, the SPwg found the red swamp crayfish in five new sites on the island, thus doubling the number of local sites of occurrence. The new Procambarus clarkii sites lie in different river basins, some of them located several hundred kilometres from the invaded areas known to date, suggesting the existence of multiple independent releases of the species in the wild. The need of better informing the local population on the risks exerted by invasive species on biological diversity, and of carefully monitoring the impact of P. clarkii on the Sicilian inland water biota is briefly stressed.

OBJECTIVES: The aim of this study was to characterize the descriptive epidemiology of insomnia in midlife and explore the relative importance of different occupational risk factors for insomnia among older workers. METHODS: A questionnaire was mailed to all adults aged 50–64 years registered with 24 English general practices. Insomnia was defined as having at least one of four problems with sleep severely in the past three months. Subjects were also asked about employment conditions, feelings concerning work, and their health. Associations were assessed by logistic regression and population attributable fractions (PAF) calculated. RESULTS: Analysis was based on 8067 respondents (5470 in paid work), 18.8% of whom reported insomnia. It was more common among women, smokers, obese individuals, those living alone, and those in financial hardship, and less prevalent among the educated, those in South-East England, and those with friendships and leisure-time pursuits. Occupational risk factors included unemployment, shift working, lack of control and support at work, job insecurity, job dissatisfaction and several of its determinants (lacking a sense of achievement, feeling unappreciated, having difficult work colleagues, feeling unfairly criticized). Population burden of insomnia was associated more strongly with difficulties in coping with work demands, job insecurity, difficult colleagues, and lack of friendships at work [population attributable fraction (PAF) 15–33%] than shift work and lack of autonomy or support (PAF 5–7%). It was strongly associated with seven measures of poorer self-assessed health. CONCLUSIONS: Employment policies aimed at tackling insomnia among older workers may benefit from focusing particularly on job–person fit, job security and relationships in the workplace.

Aging and, particularly, the onset of age-related diseases are associated with tissue dysfunction and macromolecular damage, some of which can be attributed to accumulation of oxidative damage. Recently, growing interest has emerged on the beneficial effects of plant-based diets for the prevention of chronic diseases including obesity, diabetes, and cardiovascular disease. Several studies collectively suggests that the intake of polyphenols and their major food sources may exert beneficial effects on improving insulin resistance and related diabetes risk factors, such as inflammation and oxidative stress. They are the most abundant antioxidants in the diet, and their intake has been associated with a reduced aging in humans. Polyphenolic intake has been shown to be effective at ameliorating several age-related phenotypes, including oxidative stress, inflammation, impaired proteostasis, and cellular senescence, both in vitro and in vivo. In this paper, effects of these phytochemicals (either pure forms or polyphenolic-food) are reviewed and summarized according to affected cellular signaling pathways. Finally, the effectiveness of the anti-aging preventive action of nutritional interventions based on diets rich in polyphenolic food, such as the diets of the Blue zones, are discussed.

In this study, we explored the ability of Annurca apple flesh polyphenol extract (AFPE) to affect the activity of key enzymes involved in neurodegenerative disorders—in particular, Acetyl- and Butirryl-cholinesterases, and type A and B monoamine oxidase. The effect of AFPE on enzyme activity was analyzed by in vitro enzyme assays, and the results showed concentration-dependent enzyme inhibition, with IC50 values corresponding to 859 ± 18 µM and 966 ± 72 µM for AChE and BuChE respectively, and IC50 corresponding to 145 ± 3 µM and 199 ± 7 µM for MAO-A and MAO-B, respectively, with a preference for MAO-A. Moreover, in this concentration range, AFPE did not affect the viability of human neuroblastoma SH-SY5Y and fibroblast BJ-5ta cell lines, as determined by an MTT assay. In conclusion, our results demonstrate that AFPE shows the new biological properties of inhibiting the activity of enzymes that are involved in brain functions, neurodegenerative disorders, and aging.

Recently, nutraceutical bioactive compounds in foods have been discovered for their potential health benefits regarding the prevention of chronic disorders, such as cancer, and inflammatory, cardiovascular, and metabolic diseases. Dietary omega-3 polyunsaturated fatty acids (ω-3PUFAs), including alpha-linolenic acid, docosapentaenoic acid, and eicosapentaenoic acid, are mostly attractive. They are available for the customers worldwide from commonly used foods and/or as components of commercial food supplements. The anti-inflammatory and hypotriglyceridemic effects of these fatty acids are well known, whereas pro-inflammatory properties have been recognized in their dietary counterparts, the ω-6PUFAs. Both ω-3 and ω-6PUFAs contribute to the production of lipid mediators such as endocannabinoids that are notably involved in control of food intake, energy sensing, and food–related disorders. In this review, we present ω-3 and ω-6PUFAs and their derivatives, endocannabinoids; discuss the anti-obesity effects of ω-3PUFAs; their roles in inflammation and colorectal cancer development; and how their action can be co-preventative and co-therapeutic.

The prevalence of obesity has steadily increased worldwide over the past three decades. The conventional approaches to prevent or treat this syndrome and its associated complications include a balanced diet, an increase energy expenditure, and lifestyle modification. Multiple pharmacological and non-pharmacological interventions have been developed with the aim of improving obesity complications. Recently, the use of functional foods and their bioactive components is considered a new approach in the prevention and management of this disease. Due to their biological properties, polyphenols may be considered as nutraceuticals and food supplement recommended for different syndromes. Polyphenols are a class of naturally-occurring phytochemicals, some of which have been shown to modulate physiological and molecular pathways involved in energy metabolism. Polyphenols could act in the stimulation of β-oxidation, adipocyte differentiation inhibition, counteract oxidative stress, etc. In this narrative review, we considered the association between polyphenols (resveratrol, quercetin, curcumin, and some polyphenolic extracts) and obesity, focusing on human trials. The health effects of polyphenols depend on the amount consumed and their bioavailability. Some results are contrasting, probably due to the various study designs and lengths, variation among subjects (age, gender, ethnicity), and chemical forms of the dietary polyphenols used. But, in conclusion, the data so far obtained encourage the setting of new trials, necessary to validate benefic role of polyphenols in obese individuals.

The endocannabinoid system (ES) is a cell-signalling system widely distributed in biological tissues that includes endogenous ligands, receptors, and biosynthetic and hydrolysing machineries. The impairment of the ES has been associated to several pathological conditions like behavioural, neurological, or metabolic disorders and infertility, suggesting that the modulation of this system may be critical for the maintenance of health status and disease treatment. Lifestyle and environmental factors can exert long-term effects on gene expression without any change in the nucleotide sequence of DNA, affecting health maintenance and influencing both disease load and resistance. This potentially reversible “epigenetic” modulation of gene expression occurs through the chemical modification of DNA and histone protein tails or the specific production of regulatory non-coding RNA (ncRNA). Recent findings demonstrate the epigenetic modulation of the ES in biological tissues; in the same way, endocannabinoids, phytocannabinoids, and cannabinoid receptor agonists and antagonists induce widespread or gene-specific epigenetic changes with the possibility of trans-generational epigenetic inheritance in the offspring explained by the transmission of deregulated epigenetic marks in the gametes. Therefore, this review provides an update on the epigenetics of the ES, with particular attention on the emerging role in reproduction and fertility.

Iron and vitamin D deficiencies are common during pregnancy. Our aim was to identify whether antenatal vitamin D3 supplementation affects iron status (via hepcidin suppression) and/or inflammation. Using a subset of the UK multicenter Maternal Vitamin D Osteoporosis Study (MAVIDOS)—a double-blinded, randomized, placebo-controlled trial (ISRCTN82927713; EudraCT2007-001716-23)—we performed a secondary laboratory analysis. Women with blood samples from early and late pregnancy (vitamin D3 (1000 IU/day from ~14 weeks gestation n = 93; placebo n = 102) who gave birth in the springtime (March–May) were selected as we anticipated seeing the greatest treatment group difference in change in 25-hydroxyvitamin D (25OHD) concentration. Outcomes were hepcidin, ferritin, C-reactive protein, and α1-acid glycoprotein concentration in late pregnancy (25OHD concentration was measured previously). By late pregnancy, 25OHD concentration increased by 17 nmol/L in the vitamin D3 group and decreased by 11 nmol/L in the placebo group; hepcidin, ferritin, and inflammatory markers decreased but no treatment group differences were seen. In late pregnancy, positive relationships between 25OHD and hepcidin and 25OHD and ferritin in the placebo group were observed but not in the treatment group (group × 25OHD interaction, p < 0.02). Vitamin D3 supplementation had no effect on hepcidin, ferritin, or inflammatory status suggesting no adjunctive value of vitamin D3 in reducing rates of antenatal iron deficiency.

BACKGROUND:Natural proteins undergo in vivo spontaneous post-biosynthetic deamidation of specific asparagine residues with isoaspartyl formation. Deamidated-isomerized molecules are both structurally and functionally altered. The enzyme isoaspartyl protein carboxyl-O-methyltransferase (PCMT; EC 2.1.1.77) has peculiar substrate specificity towards these deamidated proteins. It catalyzes methyl esterification of the free alpha-carboxyl group at the isoaspartyl site, thus initiating the repair of these abnormal proteins through the conversion of the isopeptide bond into a normal alpha-peptide bond. Deamidation occurs slowly during cellular and molecular aging, being accelerated by physical-chemical stresses brought to the living cells. Previous evidence supports a role of protein deamidation in the acquisition of susceptibility to apoptosis. Aim of this work was to shed a light on the role of PCMT in apoptosis clarifying the relevant mechanism(s). METHODOLOGY/PRINCIPAL FINDINGS:Endothelial cells transiently transfected with various constructs of PCMT, i.e. overexpressing wild type PCMT or negative dominants, were used to investigate the role of protein methylation during apoptosis induced by oxidative stress (H(2)O(2); 0.1-0.5 mM range). Results show that A) Cells overexpressing "wild type" human PCMT were resistant to apoptosis, whereas overexpression of antisense PCMT induces high sensitivity to apoptosis even at low H(2)O(2) concentrations. B) PCMT protective effect is specifically due to its methyltransferase activity rather than to any other non-enzymatic interactions. In fact negative dominants, overexpressing PCMT mutants devoid of catalytic activity do not prevent apoptosis. C) Cells transfected with antisense PCMT, or overexpressing a PCMT mutant, accumulate isoaspartyl-containing damaged proteins upon H(2)O(2) treatment. Proteomics allowed the identification of proteins, which are both PCMT substrates and apoptosis effectors, whose deamidation occurs under oxidative stress conditions leading to programmed cell death. These proteins, including Hsp70, Hsp90, actin, and Bcl-xL, are recognized and methylated by PCMT, according to the general repair mechanism of this methyltransferase. CONCLUSION/SIGNIFICANCE:Apoptosis can be modulated by "on/off" switch partitioning the amount of specific protein effectors, which are either in their active (native) or inactive (deamidated) molecular forms. Deamidated proteins can also be functionally restored through methylation. Bcl-xL provides a case for the role of PCMT in the maintenance of functional stability of this antiapoptotic protein.