Explore the vast range of titles available.

The observation that unhealthy diets (those that are low in whole grains, fruits and vegetables, and high in sugar, salt, saturated fat and ultra-processed foods) are a major risk factor for poor health outcomes has boosted interest in the concept of ‘food as medicine’. This concept is especially relevant to metabolic diseases, such as chronic kidney disease (CKD), in which dietary approaches are already used to ameliorate metabolic and nutritional complications. Increased awareness that toxic uraemic metabolites originate not only from intermediary metabolism but also from gut microbial metabolism, which is directly influenced by diet, has fuelled interest in the potential of ‘food as medicine’ approaches in CKD beyond the current strategies of protein, sodium and phosphate restriction. Bioactive nutrients can alter the composition and metabolism of the microbiota, act as modulators of transcription factors involved in inflammation and oxidative stress, mitigate mitochondrial dysfunction, act as senolytics and impact the epigenome by altering one-carbon metabolism. As gut dysbiosis, inflammation, oxidative stress, mitochondrial dysfunction, premature ageing and epigenetic changes are common features of CKD, these findings suggest that tailored, healthy diets that include bioactive nutrients as part of the foodome could potentially be used to prevent and treat CKD and its complications.Here, the authors discuss the mechanisms by which food and specific nutrients could affect the uraemic phenotype in chronic kidney disease (CKD). They suggest that a food-as-medicine approach could potentially be used to prevent and treat CKD and its complications.

Persistent low-grade inflammation and premature ageing are hallmarks of the uremic phenotype and contribute to impaired health status, reduced quality of life, and premature mortality in chronic kidney disease (CKD). Because there is a huge global burden of disease due to CKD, treatment strategies targeting inflammation and premature ageing in CKD are of particular interest. Several distinct features of the uremic phenotype may represent potential treatment options to attenuate the risk of progression and poor outcome in CKD. The nuclear factor erythroid 2-related factor 2 (NRF2)–kelch-like erythroid cell-derived protein with CNC homology [ECH]-associated protein 1 (KEAP1) signaling pathway, the endocrine phosphate-fibroblast growth factor-23–klotho axis, increased cellular senescence, and impaired mitochondrial biogenesis are currently the most promising candidates, and different pharmaceutical compounds are already under evaluation. If studies in humans show beneficial effects, carefully phenotyped patients with CKD can benefit from them.

A systematic review following PRISMA guidelines was conducted to answer the question: What epigenetic, telomeric and associated biological changes are associated with exposure to adverse childhood experiences (ACEs) in the under 12s? Using PRISMA guidelines, appropriate databases were searched. 190 papers were returned with 38 articles fully reviewed. Articles were each independently quality rated by two authors using the Crowe Critical Appraisal Tool and data were extracted. Of the 38 articles, 23 were rated as very high quality. Most study participants were adults (n = 7769) with n = 727 child participants. Only seven of the very/high-quality studies were prospective and involved children. Methylation was the most studied method of epigenetic modification. There is some evidence supporting epigenetic modification of certain markers in participants exposed to ACEs measured in adulthood. Research is lacking on non-coding aspects of the epigenome and on coding aspects other than DNA methylation. There is some evidence of a more powerful effect on telomere length if physical neglect was involved. Much further work is required to model biological and psychological effects of epigenetic changes during childhood using prospective study designs. The effect of ACEs on the cellular ageing process during childhood is inadequately investigated and relies solely on measure of telomere length. Future research suggestions are proposed.

There is a substantial gap in health and longevity between more affluent and more deprived areas, and more knowledge of the determinants of this health divide is required. Experience of the local residential environment is important for health although few studies have examined this in relation to biological markers of age such as telomere length. We sought to examine if residents' perceptions of neighbourhood stressors over time were associated with telomere length in a community study. In a prospective cohort study of 2186 adults in the West of Scotland, we measured neighbourhood stressors at three time points over a 12-year period and telomere length at the end of the study. Using linear regression models, we found that a higher accumulation of neighbourhood stressors over time was associated with shorter telomere length, even after taking cohort, social class, health behaviours (smoking status, diet, physical activity), BMI and depression into account among females only (Beta = 0.007; 95%CI [0.001, 0.012]; P<0.014). Neighborhood environments are potentially modifiable, and future efforts directed towards improving deleterious local environments may be useful to lessen telomere attrition.

Telomere biology, a key component of the hallmarks of ageing, offers insight into dysregulation of normative ageing processes that accompany age-related diseases such as cancer. Telomere homeostasis is tightly linked to cellular metabolism, and in particular with mitochondrial physiology, which is also diminished during cellular senescence and normative physiological ageing. Inherent in the biochemistry of these processes is the role of magnesium, one of the main cellular ions and an essential cofactor in all reactions that use ATP. Magnesium plays an important role in many of the processes involved in regulating telomere structure, integrity and function. This review explores the mechanisms that maintain telomere structure and function, their influence on circadian rhythms and their impact on health and age-related disease. The pervasive role of magnesium in telomere homeostasis is also highlighted.

Many of the >2 million animal species that inhabit Earth have developed survival mechanisms that aid in the prevention of obesity, kidney disease, starvation, dehydration and vascular ageing; however, some animals remain susceptible to these complications. Domestic and captive wild felids, for example, show susceptibility to chronic kidney disease (CKD), potentially linked to the high protein intake of these animals. By contrast, naked mole rats are a model of longevity and are protected from extreme environmental conditions through mechanisms that provide resistance to oxidative stress. Biomimetic studies suggest that the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) offers protection in extreme environmental conditions and promotes longevity in the animal kingdom. Similarly, during months of fasting, immobilization and anuria, hibernating bears are protected from muscle wasting, azotaemia, thrombotic complications, organ damage and osteoporosis -- features that are often associated with CKD. Improved understanding of the susceptibility and protective mechanisms of these animals and others could provide insights into novel strategies to prevent and treat several human diseases, such as CKD and ageing-associated complications. An integrated collaboration between nephrologists and experts from other fields, such as veterinarians, zoologists, biologists, anthropologists and ecologists, could introduce a novel approach for improving human health and help nephrologists to find novel treatment strategies for CKD.

A prematurely aged phenotype is a common characteristic of chronic kidney disease (CKD) and other chronic organ diseases, including heart failure and rheumatoid arthritis. In this opinion article, the authors suggest four major pathophysiological mechanisms that may underlie premature ageing in CKD. Chronic kidney disease (CKD) shares many phenotypic similarities with other chronic diseases, including heart failure, chronic obstructive pulmonary disease, HIV infection and rheumatoid arthritis. The most apparent similarity is premature ageing, involving accelerated vascular disease and muscle wasting. We propose that in addition to a sedentary lifestyle and psychosocial and socioeconomic determinants, four major disease-induced mechanisms underlie premature ageing in CKD: an increase in allostatic load, activation of the 'stress resistance response', activation of age-promoting mechanisms and impairment of anti-ageing pathways. The most effective current interventions to modulate premature ageing—treatment of the underlying disease, optimal nutrition, correction of the internal environment and exercise training—reduce systemic inflammation and oxidative stress and induce muscle anabolism. Deeper mechanistic insight into the phenomena of premature ageing as well as early diagnosis of CKD might improve the application and efficacy of these interventions and provide novel leads to combat muscle wasting and vascular impairment in chronic diseases.

There is evidence that child maltreatment is associated with shorter telomere length in early life. This study aims to examine if child maltreatment is associated with telomere length in middle- and older-age adults. This was a retrospective cohort study of 141 748 UK Biobank participants aged 37-73 years at recruitment. Leukocyte telomere length was measured with quantitative polymerase chain reaction, and log-transformed and scaled to have unit standard deviation. Child maltreatment was recalled by participants. Linear regression was used to analyse the association. After adjusting for sociodemographic characteristics, participants with three or more types of maltreatment presented with the shortest telomere lengths ( = -0.05, 95% CI -0.07 to -0.03; < 0.0001), followed by those with two types of maltreatment ( = -0.02, 95% CI -0.04 to 0.00; = 0.02), referent to those who had none. When adjusted for depression and post-traumatic stress disorder, the telomere lengths of participants with three or more types of maltreatment were still shorter ( = -0.04, 95% CI -0.07 to -0.02; = 0.0008). The telomere lengths of those with one type of maltreatment were not significantly different from those who had none. When mutually adjusted, physical abuse ( = -0.05, 95% CI -0.07 to -0.03; < 0.0001) and sexual abuse ( = -0.02, 95% CI -0.04 to 0.00; = 0.02) were independently associated with shorter telomere length. Our findings showed that child maltreatment is associated with shorter telomere length in middle- and older-aged adults, independent of sociodemographic and mental health factors.

Key Points The incidence of deaths owing to renal dysfunction is increasing globally in parallel with the ageing population The epigenetic landscape of ageing is mediated by dynamic changes in the methylome and in chromatin structure, along with coordinated regulation of a complex range of molecular processes by noncoding RNAs in response to environmental changes A mechanistic link is emerging between the epigenetic landscape of ageing and renal dysfunction based on regulation of ageing processes that are common across taxa Epigenetic regulation of biological ageing in the kidney is influenced directly by nutrition, inflammation, the gut microbiome, psychosocial factors and lifestyle factors Models of progeria provide important hypothesis-generating insights for future therapies designed to modify the epigenetic landscape in ageing and disease Epigenetic interventions could potentially improve renal health, but caution is warranted given the potential for intergenerational and transgenerational effects Epigenetic factors control gene expression and activity in response to environmental perturbation and regulate ageing processes throughout the life course. Here, the authors discuss the epigenetic regulation of signalling pathways that modulate ageing and their impact on the kidney. An ability to separate natural ageing processes from processes specific to morbidities is required to understand the heterogeneity of age-related organ dysfunction. Mechanistic insight into how epigenetic factors regulate ageing throughout the life course, linked to a decline in renal function with ageing, is already proving to be of value in the analyses of clinical and epidemiological cohorts. Noncoding RNAs provide epigenetic regulatory circuits within the kidney, which reciprocally interact with DNA methylation processes, histone modification and chromatin. These interactions have been demonstrated to reflect the biological age and function of renal allografts. Epigenetic factors control gene expression and activity in response to environmental perturbations. They also have roles in highly conserved signalling pathways that modulate ageing, including the mTOR and insulin/insulin-like growth factor signalling pathways, and regulation of sirtuin activity. Nutrition, the gut microbiota, inflammation and environmental factors, including psychosocial and lifestyle stresses, provide potential mechanistic links between the epigenetic landscape of ageing and renal dysfunction. Approaches to modify the renal epigenome via nutritional intervention, targeting the methylome or targeting chromatin seem eminently feasible, although caution is merited owing to the potential for intergenerational and transgenerational effects.

The sirtuin gene family has been linked with tumourigenesis, in both a tumour promoter and suppressor capacity. Information regarding the function of sirtuins in pancreatic cancer is sparse and equivocal. We undertook a novel study investigating SIRT1-7 protein expression in a cohort of pancreatic tumours. The aim of this study was to establish a protein expression profile for SIRT1-7 in pancreatic ductal adenocarcinomas (PDAC) and to determine if there were associations between SIRT1-7 expression, clinico-pathological parameters and patient outcome. Immunohistochemical analysis of SIRT1-7 protein levels was undertaken in a tissue micro-array comprising 77 resected PDACs. Statistical analyses determined if SIRT1-7 protein expression was associated with clinical parameters or outcome. Two sirtuin family members demonstrated significant associations with clinico-pathological parameters and patient outcome. Low level SIRT3 expression in the tumour cytoplasm correlated with more aggressive tumours, and a shorter time to relapse and death, in the absence of chemotherapeutic intervention. Low levels of nuclear SIRT7 expression were also associated with an aggressive tumour phenotype and poorer outcome, as measured by disease-free and disease-specific survival time, 12 months post-diagnosis. Our data suggests that SIRT3 and SIRT7 possess tumour suppressor properties in the context of pancreatic cancer. SIRT3 may also represent a novel predictive biomarker to determine which patients may or may not respond to chemotherapy. This study opens up an interesting avenue of investigation to potentially identify predictive biomarkers and novel therapeutic targets for pancreatic cancer, a disease that has seen no significant improvement in survival over the past 40 years.