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1.
Inflammation, a Double-Edge Sword for Cancer and Other Age-Related Diseases.
Gupta, SC, Kunnumakkara, AB, Aggarwal, S, Aggarwal, BB
Frontiers in immunology. 2018;:2160
Abstract
Increasing evidence from diverse sources during the past several years has indicated that long-term, low level, chronic inflammation mediates several chronic diseases including cancer, arthritis, obesity, diabetes, cardiovascular diseases, and neurological diseases. The inflammatory molecules and transcription factors, adhesion molecules, AP-1, chemokines, C-reactive protein (CRP), cyclooxygenase (COX)-2, interleukins (ILs), 5-lipooxygenase (5-LOX), matrix metalloproteinases (MMPs), nuclear factor (NF)-kB, signal transducer and activator of transcription 3 (STAT3), tumor necrosis factor (TNF), and vascular endothelial growth factor (VEGF) are molecular links between inflammation and chronic diseases. Thus, suppression of inflammatory molecules could be potential strategy for the prevention and therapy of chronic diseases. The currently available drugs against chronic diseases are highly expensive, minimally effective and produce several side effects when taken for long period of time. The focus of this review is to discuss the potential of nutraceuticals derived from "Mother Nature" such as apigenin, catechins, curcumin, ellagic acid, emodin, epigallocatechin gallate, escin, fisetin, flavopiridol, genistein, isoliquiritigenin, kaempferol, mangostin, morin, myricetin, naringenin, resveratrol, silymarin, vitexin, and xanthohumol in suppression of these inflammatory pathways. Thus, these nutraceuticals offer potential in preventing or delaying the onset of chronic diseases. We provide evidence for the potential of these nutraceuticals from pre-clinical and clinical studies.
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2.
The ageing pancreas: a systematic review of the evidence and analysis of the consequences.
Löhr, JM, Panic, N, Vujasinovic, M, Verbeke, CS
Journal of internal medicine. 2018;(5):446-460
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Abstract
Senior people constitute the fastest growing segment of the population. The elderly are at risk for malnutrition, thought to be caused by reduced food intake or involution of the physiological capacity of the GI tract. Age-related changes are well known in other secretory organs such as liver, kidney and intestine. The pancreas, representing a metabolically active organ with uptake and breakdown of essential nutritional components, changes its morphology and function with age. During childhood, the volume of the pancreas increases, reaching a plateau between 20 and 60 years, and declines thereafter. This decline involves the pancreatic parenchyma and is associated with decreased perfusion, fibrosis and atrophy. As a consequence of these changes, pancreatic exocrine function is impaired in healthy older individuals without any gastrointestinal disease. Five per cent of people older than 70 years and ten per cent older than 80 years have pancreatic exocrine insufficiency (PEI) with a faecal elastase-1 below 200 μg g-1 stool, and 5% have severe PEI with faecal elastase-1 below 100 μg g-1 stool. This may lead to maldigestion and malnutrition. Patients may have few symptoms, for example steatorrhoea, diarrhoea, abdominal pain and weight loss. Malnutrition consists of deficits of fat-soluble vitamins and is affecting both patients with PEI and the elderly. Secondary consequences may include decreased bone mineral density and results from impaired absorption of fat-soluble vitamin D due to impaired pancreatic exocrine function. The unanswered question is whether this age-related decrease in pancreatic function warrants therapy. Therapeutic intervention, which may consist of supplementation of pancreatic enzymes and/or vitamins in aged individuals with proven exocrine pancreas insufficiency, could contribute to healthy ageing.
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3.
Iron status in the elderly: A review of recent evidence.
Wawer, AA, Jennings, A, Fairweather-Tait, SJ
Mechanisms of ageing and development. 2018;:55-73
Abstract
A comprehensive literature review of iron status in the elderly was undertaken in order to update a previous review (Fairweather-Tait et al, 2014); 138 summarised papers describe research on the magnitude of the problem, aetiology and age-related physiological changes that may affect iron status, novel strategies for assessing iron status with concurrent health conditions, hepcidin, lifestyle factors, iron supplements, iron status and health outcomes (bone mineral density, frailty, inflammatory bowel disease, kidney failure, cancer, cardiovascular, and neurodegenerative diseases). Each section of this review concludes with key points from the relevant papers. The overall findings were that disturbed iron metabolism plays a major role in a large number of conditions associated with old age. Correction of iron deficiency/overload may improve disease prognosis, but diagnosis of iron deficiency requires appropriate cut-offs for biomarkers of iron status in elderly men and women to be agreed. Iron deficiency (with or without anemia), anemia of inflammation, and anemia of chronic disease are all widespread in the elderly and, once identified, should be investigated further as they are often indicative of underlying disease. Management options should be reviewed and updated, and novel therapies, which show potential for treating anemia of inflammation or chronic disease, should be considered.
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4.
Diet, nutrition and the ageing brain: current evidence and new directions.
Moore, K, Hughes, CF, Ward, M, Hoey, L, McNulty, H
The Proceedings of the Nutrition Society. 2018;(2):152-163
Abstract
Globally populations are ageing. By 2050, it is estimated that there will be two billion people aged 60 years or over, of which 131 million are projected to be affected by dementia, while depression is predicted to be the second leading cause of disability worldwide by 2020. Preventing or delaying the onset of these disorders should therefore be a public health priority. There is some evidence linking certain dietary patterns, particularly the Mediterranean diet, with a reduced risk of dementia and depression. Specific dietary components have also been investigated in relation to brain health, with emerging evidence supporting protective roles for n-3 PUFA, polyphenols, vitamin D and B-vitamins. At this time, the totality of evidence is strongest in support of a role for folate and the metabolically related B-vitamins (vitamin B12, vitamin B6 and riboflavin) in slowing the progression of cognitive decline and possibly reducing the risk of depression in ageing. Future studies incorporating new technologies, such as MRI and magnetoencephalography, offer much promise in identifying effective nutrition interventions that could reduce the risk of cognitive and mental disorders. This review will explore the ageing brain and the emerging evidence linking diet and specific nutrients with cognitive function and depression in ageing, with the potential to develop strategies that could improve quality of life in our ageing population.
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5.
Is evolutionary loss our gain? The role of ACTN3 p.Arg577Ter (R577X) genotype in athletic performance, ageing, and disease.
Houweling, PJ, Papadimitriou, ID, Seto, JT, Pérez, LM, Coso, JD, North, KN, Lucia, A, Eynon, N
Human mutation. 2018;(12):1774-1787
Abstract
A common null polymorphism in the ACTN3 gene (rs1815739:C>T) results in replacement of an arginine (R) with a premature stop codon (X) at amino acid 577 in the fast muscle protein α-actinin-3. The ACTN3 p.Arg577Ter allele (aka p.R577* or R577X) has undergone positive selection, with an increase in the X allele frequency as modern humans migrated out of Africa into the colder, less species-rich Eurasian climates suggesting that the absence of α-actinin-3 may be beneficial in these conditions. Approximately 1.5 billion people worldwide are completely deficient in α-actinin-3. While the absence of α-actinin-3 influences skeletal muscle function and metabolism this does not result in overt muscle disease. α-Actinin-3 deficiency (ACTN3 XX genotype) is constantly underrepresented in sprint/power performance athletes. However, recent findings from our group and others suggest that the ACTN3 R577X genotype plays a role beyond athletic performance with effects observed in ageing, bone health, and inherited muscle disorders such as McArdle disease and Duchenne muscle dystrophy. In this review, we provide an update on the current knowledge regarding the influence of ACTN3 R577X on skeletal muscle function and its potential biological and clinical implications. We also outline future research directions to explore the role of α-actinin-3 in healthy and diseased populations.
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The Molecular Mechanisms and Prevention Principles of Muscle Atrophy in Aging.
Zhang, Y, Pan, X, Sun, Y, Geng, YJ, Yu, XY, Li, Y
Advances in experimental medicine and biology. 2018;:347-368
Abstract
Muscle atrophy in aging is characterized by progressive loss of muscle mass and function. Muscle mass is determined by the balance of synthesis and degradation of protein, which are regulated by several signaling pathways such as ubiquitin-proteasome system, autophagy-lysosome systems, oxidative stress, proinflammatory cytokines, hormones, and so on. Sufficient nutrition can enhance protein synthesis, while exercise can improve the quality of life in the elderly. This chapter will discuss the epidemiology, pathogenesis, as well as the current treatment for aging-induced muscular atrophy.
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7.
A network-based meta-analysis for characterizing the genetic landscape of human aging.
Blankenburg, H, Pramstaller, PP, Domingues, FS
Biogerontology. 2018;(1):81-94
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Abstract
Great amounts of omics data are generated in aging research, but their diverse and partly complementary nature requires integrative analysis approaches for investigating aging processes and connections to age-related diseases. To establish a broader picture of the genetic and epigenetic landscape of human aging we performed a large-scale meta-analysis of 6600 human genes by combining 35 datasets that cover aging hallmarks, longevity, changes in DNA methylation and gene expression, and different age-related diseases. To identify biological relationships between aging-associated genes we incorporated them into a protein interaction network and characterized their network neighborhoods. In particular, we computed a comprehensive landscape of more than 1000 human aging clusters, network regions where genes are highly connected and where gene products commonly participate in similar processes. In addition to clusters that capture known aging processes such as nutrient-sensing and mTOR signaling, we present a number of clusters with a putative functional role in linking different aging processes as promising candidates for follow-up studies. To enable their detailed exploration, all datasets and aging clusters are made freely available via an interactive website ( https://gemex.eurac.edu/bioinf/age/ ).
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Constipation in the elderly from Northern Sardinia is positively associated with depression, malnutrition and female gender.
Dore, MP, Pes, GM, Bibbò, S, Tedde, P, Bassotti, G
Scandinavian journal of gastroenterology. 2018;(7):797-802
Abstract
OBJECTIVES Constipation is a common complaint in older adults. The rise in life expectancy may amplify the problem and increase social expenditure. We investigated the major risk factors associated with constipation in a large sample of elderly. METHODS Outpatients from Northern Sardinia attending a Geriatric Unit between 2001 and 2014 were enrolled. Demographic and anthropometric data, income, education and self-reported bowel function were collected. The presence of constipation was adjusted for cognitive status, assessed by the Mini-Mental State Examination (MMSE) test; single and cumulative illness rating scale (CIRS); current or past symptomatic depression and anxiety measured by the Geriatric Depression Scale (GDS); nutritional status, evaluated using the Mini-Nutritional Assessment (MNA); type and number of different medications used. RESULTS 1328 elderly patients (mean age 77.7 ± 7.2 years) were enrolled. Constipation was present in 32.1%, more commonly in women (35.4% vs 28.3%) and increased with age. The multivariate analysis showed a significantly greater risk of constipation in patients with a risk of malnutrition (OR = 1.745, 95% CI: 1.043-2.022; p = .034), female gender (OR = 1.735, 95% CI: 1.068-2.820; p = .026) and depression (OR = 1.079, 95% CI: 1.022-1.140; p = .006). Other potential predisposing factors assessed such as MMSE, CIRS, body mass index, marital status, smoking habit, education, income and number of taken drugs did not show a statistically significant association. Aging was a risk for constipation also in patients free of medications. CONCLUSIONS Knowledge of risk factors associated with bowel alterations in elderly individuals may provide important clues for caregivers to prevent or reduce constipation.
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Understanding Age-Induced Cortical Porosity in Women: The Accumulation and Coalescence of Eroded Cavities Upon Existing Intracortical Canals Is the Main Contributor.
Andreasen, CM, Delaisse, JM, van der Eerden, BC, van Leeuwen, JP, Ding, M, Andersen, TL
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2018;(4):606-620
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Abstract
Intracortical bone remodeling normally ensures maintenance of the cortical bone matrix and strength, but during aging, this remodeling generates excessive porosity. The mechanism behind the age-induced cortical porosity is poorly understood and addressed in the present study. This study consists of a histomorphometric analysis of sections of iliac bone specimens from 35 women (age 16-78 years). First, the study shows that the age-induced cortical porosity reflects an increased pore size rather than an increased pore density. Second, it establishes a novel histomorphometric classification of the pores, which is based on the characteristics of the remodeling sites to which each pore is associated. It takes into consideration (i) the stage of the remodeling event at the level where the pore is sectioned, (ii) whether the event corresponds with the generation of a new pore through penetrative tunneling (type 1 pores) or with remodeling of an existing pore (type 2 pores), and (iii) in the latter case, whether or not the new remodeling event leads to the coalescence of pores. Of note, the advantage of this classification is to relate porosity with its generation mechanism. Third, it demonstrates that aging and porosity are correlated with: a shift from type 1 to type 2 pores, reflecting that the remodeling of existing pores is higher; an accumulation of eroded type 2 pores, reflecting an extended resorption-reversal phase; and a coalescence of these eroded type 2 pores into enlarged coalescing type 2 cavities. Collectively, this study supports the notion, that age-related increase in cortical porosity is the result of intracortical remodeling sites upon existing pores, with an extended reversal-resorption phase (eroded type 2 pores) that may likely result in a delayed or absent initiation of the subsequent bone formation. © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.
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Individual testosterone decline and future mortality risk in men.
Holmboe, SA, Skakkebæk, NE, Juul, A, Scheike, T, Jensen, TK, Linneberg, A, Thuesen, BH, Andersson, AM
European journal of endocrinology. 2018;(1):123-130
Abstract
OBJECTIVE Male aging is characterized by a decline in testosterone (TS) levels with a substantial variability between subjects. However, it is unclear whether differences in age-related changes in TS are associated with general health. We investigated associations between mortality and intra-individual changes in serum levels of total TS, SHBG, free TS and LH during a ten-year period with up to 18 years of registry follow-up. DESIGN 1167 men aged 30-60 years participating in the Danish Monitoring Trends and Determinants of Cardiovascular Disease (MONICA1) study and who had a follow-up examination ten years later (MONICA10) were included. From MONICA10, the men were followed up to 18 years (mean: 15.2 years) based on the information from national mortality registries via their unique personal ID numbers. METHODS Cox proportional hazard models were used to investigate the association between intra-individual hormone changes and all-cause, CVD and cancer mortalities. RESULTS A total of 421 men (36.1%) died during the follow-up period. Men with most pronounced decline in total TS (<10th percentile) had a higher all-cause mortality risk compared to men within the 10th to 90th percentile (hazard ratio (HR): 1.60; 95% confidence interval (CI): 1.08-2.36). No consistent associations were seen in cause-specific mortality analyses. CONCLUSION Our study showed that higher mortality rates were seen among the men who had the most pronounced age-related decline in TS, independent of their baseline TS levels.