Lessons from Sicilian Centenarians for Anti-Ageing Medicine. The Oxi-Inflammatory Status
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PROVIDER: S-EPMC9673988 | biostudies-literature | 2022 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundAge-related physiological changes in the gastrointestinal tract, as well as modifications in lifestyle, nutritional behaviour, and functionality of the host immune system, inevitably affect the gut microbiota, resulting in a greater susceptibility to infections.Methodology/principal findingsBy using the Human Intestinal Tract Chip (HITChip) and quantitative PCR of 16S rRNA genes of Bacteria and Archaea, we explored the age-related differences in the gut microbiota composition among young adults, elderly, and centenarians, i.e subjects who reached the extreme limits of the human lifespan, living for over 100 years. We observed that the microbial composition and diversity of the gut ecosystem of young adults and seventy-years old people is highly similar but differs significantly from that of the centenarians. After 100 years of symbiotic association with the human host, the microbiota is characterized by a rearrangement in the Firmicutes population and an enrichment in facultative anaerobes, notably pathobionts. The presence of such a compromised microbiota in the centenarians is associated with an increased inflammatory status, also known as inflammageing, as determined by a range of peripheral blood inflammatory markers. This may be explained by a remodelling of the centenarians' microbiota, with a marked decrease in Faecalibacterium prauznitzii and relatives, symbiotic species with reported anti-inflammatory properties. As signature bacteria of the long life we identified specifically Eubacterium limosum and relatives that were more than ten-fold increased in the centenarians.Conclusions/significanceWe provide evidence for the fact that the ageing process deeply affects the structure of the human gut microbiota, as well as its homeostasis with the host's immune system. Because of its crucial role in the host physiology and health status, age-related differences in the gut microbiota composition may be related to the progression of diseases and frailty in the elderly population.
| S-EPMC2871786 | biostudies-literature
Project description:The demographic and social changes of the past decades have determined improvements in public health and longevity. So, the number of centenarians is increasing as a worldwide phenomenon. Scientists have focused their attention on centenarians as optimal model to address the biological mechanisms of "successful and unsuccessful ageing". They are equipped to reach the extreme limits of human life span and, most importantly, to show relatively good health, being able to perform their routine daily life and to escape fatal age-related diseases, such as cardiovascular diseases and cancer. Thus, particular attention has been centered on their genetic background and immune system. In this review, we report our data gathered for over 10 years in Sicilian centenarians. Based on results obtained, we suggest longevity as the result of an optimal performance of immune system and an over-expression of anti-inflammatory sequence variants of immune/inflammatory genes. However, as well known, genetic, epigenetic, stochastic and environmental factors seem to have a crucial role in ageing and longevity. Epigenetics is associated with ageing, as demonstrated in many studies. In particular, ageing is associated with a global loss of methylation state. Thus, the aim of future studies will be to analyze the weight of epigenetic changes in ageing and longevity.
| S-EPMC3402998 | biostudies-literature
Project description:Current literature agrees on the notion that efficient DNA repair favors longevity across evolution. The DNA damage response machinery activates inflammation and type I interferon signaling. Both pathways play an acknowledged role in the pathogenesis of a variety of age-related diseases and are expected to be detrimental for human longevity. Here, we report on the anti-inflammatory molecular make-up of centenarian's fibroblasts (low levels of IL-6, type 1 interferon beta, and pro-inflammatory microRNAs), which is coupled with low level of DNA damage (measured by comet assay and histone-2AX activation) and preserved telomere length. In the same cells, high levels of the RNAseH2C enzyme subunit and low amounts of RNAseH2 substrates, i.e. cytoplasmic RNA:DNA hybrids are present. Moreover, RNAseH2C locus is hypo-methylated and RNAseH2C knock-down up-regulates IL-6 and type 1 interferon beta in centenarian's fibroblasts. Interestingly, RNAseH2C locus is hyper-methylated in vitro senescent cells and in tissues from atherosclerotic plaques and breast tumors. Finally, extracellular vesicles from centenarian's cells up-regulate RNAseH2C expression and dampen the pro-inflammatory phenotype of fibroblasts, myeloid, and cancer cells. These data suggest that centenarians are endowed with restrained DNA damage-induced inflammatory response, that may facilitate their escape from the deleterious effects of age-related chronic inflammation.
| S-EPMC6748076 | biostudies-literature
Project description:People are living longer, but lifespan increase does not coincide with a boost in health-span. Thus, improving the quality of life of older people is a priority. Centenarians reach extreme longevity in a relatively good health status, escaping or delaying fatal or strongly invalidating diseases. Therefore, studying processes involved in longevity is important to explain the biological mechanisms of health and well-being, since knowledge born from this approach can provide valuable information on how to slow aging. We performed the present study in a well characterized very homogeneous sample of 173 people from Western Sicily, to update existing literature on some phenotypic aspects of aging and longevity and to propose a range of values for older people. We classified 5 age groups, from young adults to centenarians, to understand the age and gender-related variations of the different parameters under study. We collected anamnestic data and performed anthropometric, bioimpedance, molecular, haematological, oxidative, and hematochemical tests, adopting a multidimensional analysis approach. An important evidence of the present study is that there are differences related to both age and gender in several biomarkers. Indeed, gender differences seem to be still poorly considered and inadequately investigated in aging as well as in other medical studies. Moreover, we often observed comparable parameters between young and centenarians rather than non-agenarians and centenarians, hypothesizing a sort of slowdown, almost followed by a reversal trend, in the decay of systemic deterioration. The study of centenarians provides important indications on how to slow aging, with benefits for those who are more vulnerable to disease and disability. The identification of the factors that predispose to a long and healthy life is of enormous interest for translational medicine in an aging world.
| S-EPMC8460304 | biostudies-literature
Project description:BackgroundIn recent years an increasing number of public investments and policy changes have been made to improve the availability, affordability and quality of medicines available to consumers in developing countries, including anti-malarials. It is important to monitor the extent to which these interventions are successful in achieving their aims using quantitative data on the supply side of the market. There are a number of challenges related to studying supply, including outlet sampling, gaining provider cooperation and collecting accurate data on medicines. This paper provides guidance on key steps to address these issues when conducting a medicine outlet survey in a developing country context. While the basic principles of good survey design and implementation are important for all surveys, there are a set of specific issues that should be considered when conducting a medicine outlet survey.MethodsThis paper draws on the authors' experience of designing and implementing outlet surveys, including the lessons learnt from ACTwatch outlet surveys on anti-malarial retail supply, and other key studies in the field. Key lessons and points of debate are distilled around the following areas: selecting a sample of outlets; techniques for collecting and analysing data on medicine availability, price and sales volumes; and methods for ensuring high quality data in general.Results and conclusionsThe authors first consider the inclusion criteria for outlets, contrasting comprehensive versus more focused approaches. Methods for developing a reliable sampling frame of outlets are then presented, including use of existing lists, key informants and an outlet census. Specific issues in the collection of data on medicine prices and sales volumes are discussed; and approaches for generating comparable price and sales volume data across products using the adult equivalent treatment dose (AETD) are explored. The paper concludes with advice on practical considerations, including questionnaire design, field worker training, and data collection. Survey materials developed by ACTwatch for investigating anti-malarial markets in sub-Saharan Africa and Asia provide a helpful resource for future studies in this area.
| S-EPMC3599752 | biostudies-literature
Project description:BackgroundThere is a growing interest in the role of inflammageing for chronic disease development. Cytokines are potent soluble immune mediators that can be used as target biomarkers of inflammageing; however, their measurement in human samples has been challenging. This study aimed to assess the reliability of a pro- and anti-inflammatory cytokine panel in a sample of healthy people measured with a novel electrochemiluminescent multiplex immunoassay platform (Meso Scale Discovery, MSD), and to characterize their associations with metabolic and inflammatory phenotypes.ResultsOverall, the majority of cytokines were above the limit of detection (in at least 85.3% of the samples). Cytokines IL-6, IL-8, TNF-α, IL-10, IL-13, and IFN-γ showed overall good to fair reliability (ICC > 0.40), whereas IL-1β, IL-2, IL-4, and IL-12p70 showed poor reliability (ICC < 0.40). The reliability estimates were not substantially influenced by participants' age, sex, obesity and C-reactive protein (CRP) levels. As expected, cytokine concentrations were elevated with advanced age most pronouncedly for IL-6, IL-8, Il-2, IFN- γ, and TNF-α. No major associations with metabolic phenotypes were observed for most cytokines, with the exception of a positive association between IL-6 and TNF-α with body mass index and CRP (ρ: 0.36; ρ: 0.20; ρ: 0.53; ρ: 0.22, respectively), and IFN-γ and IL-10 with CRP (ρ: 0.23 and ρ: 0.19, respectively).ConclusionsSingle measurements of selected cytokines using MSD platform, including IL-6, IL-8, IL-10, IL-13, TNF-α, and IFN-γ have shown to be representative of an individual's average level over time and could be suitable for use in prospective epidemiological and clinical studies. Such studies are highly warranted to characterize associations of cytokines with phenotypes and diseases associated with ageing.
| S-EPMC6530020 | biostudies-literature
Project description:Background: The environment can alter the homeostasis of humans and human microbiota. Oral health is influenced by high altitude through symptoms of periodontitis, barodontalgia, dental barotrauma, and a decrease in salivary flow. Microbiota and inflammatory state are connected in the oral cavity. This study aimed to explore the effect of acute high-altitude exposure on the salivary microbiome and inflammatory indicators. Methods: Fifteen healthy expeditioners were subjected to oral examination, recording the plaque index (PII), gingival index (GI), the simplified oral hygiene index (OHI-S), and the number of teeth; unstimulated saliva samples were collected at an altitude of 1191 m (T1) and 4556 m (T2). TNF-α, sICAM1, ROS, and the oral bacterial species Porphyromonas gingivalis (Pg) and Fusobacterium nucleatum (Fn) were quantified. Results: At T2, slCAM, TNF, and ROS increased by 85.5% (IQR 74%), 84% (IQR 409.25%), and 53.5% (IQR 68%), respectively, while Pg decreased by 92.43% (IQR 102.5%). The decrease in Pg was greater in the presence of low OHI-S. The increase in slCAM1 correlated with the reduction in Fn. Individuals with high GI and OHI-S had a limited increase in TNF-α at T2. Conclusion: Short-term exposures can affect the concentration of pathogenic periodontal bacteria and promote local inflammation.
| S-EPMC11508378 | biostudies-literature
Project description:RationaleThe diabetes mellitus drug metformin is under investigation in cardiovascular disease, but the molecular mechanisms underlying possible benefits are poorly understood.ObjectiveHere, we have studied anti-inflammatory effects of the drug and their relationship to antihyperglycemic properties.Methods and resultsIn primary hepatocytes from healthy animals, metformin and the IKKβ (inhibitor of kappa B kinase) inhibitor BI605906 both inhibited tumor necrosis factor-α-dependent IκB degradation and expression of proinflammatory mediators interleukin-6, interleukin-1β, and CXCL1/2 (C-X-C motif ligand 1/2). Metformin suppressed IKKα/β activation, an effect that could be separated from some metabolic actions, in that BI605906 did not mimic effects of metformin on lipogenic gene expression, glucose production, and AMP-activated protein kinase activation. Equally AMP-activated protein kinase was not required either for mitochondrial suppression of IκB degradation. Consistent with discrete anti-inflammatory actions, in macrophages, metformin specifically blunted secretion of proinflammatory cytokines, without inhibiting M1/M2 differentiation or activation. In a large treatment naive diabetes mellitus population cohort, we observed differences in the systemic inflammation marker, neutrophil to lymphocyte ratio, after incident treatment with either metformin or sulfonylurea monotherapy. Compared with sulfonylurea exposure, metformin reduced the mean log-transformed neutrophil to lymphocyte ratio after 8 to 16 months by 0.09 U (95% confidence interval, 0.02-0.17; P=0.013) and increased the likelihood that neutrophil to lymphocyte ratio would be lower than baseline after 8 to 16 months (odds ratio, 1.83; 95% confidence interval, 1.22-2.75; P=0.00364). Following up these findings in a double-blind placebo controlled trial in nondiabetic heart failure (trial registration: NCT00473876), metformin suppressed plasma cytokines including the aging-associated cytokine CCL11 (C-C motif chemokine ligand 11).ConclusionWe conclude that anti-inflammatory properties of metformin are exerted irrespective of diabetes mellitus status. This may accelerate investigation of drug utility in nondiabetic cardiovascular disease groups.Clinical trial registrationName of the trial registry: TAYSIDE trial (Metformin in Insulin Resistant Left Ventricular [LV] Dysfunction). URL: https://www.clinicaltrials.gov. Unique identifier: NCT00473876.
| S-EPMC4990459 | biostudies-literature
Project description:Curcumin is a natural compound with great potential for disease treatment. A large number of studies have proved that curcumin has a variety of biological activities, among which anti-inflammatory effect is a significant feature of it. Inflammation is a complex and pervasive physiological and pathological process. The physiological and pathological mechanisms of inflammatory bowel disease, psoriasis, atherosclerosis, COVID-19 and other research focus diseases are not clear yet, and they are considered to be related to inflammation. The anti-inflammatory effect of curcumin can effectively improve the symptoms of these diseases and is expected to be a candidate drug for the treatment of related diseases. This paper mainly reviews the anti-inflammatory effect of curcumin, the inflammatory pathological mechanism of related diseases, the regulatory effect of curcumin on these, and the latest research results on the improvement of curcumin pharmacokinetics. It is beneficial to the further study of curcumin and provides new ideas and insights for the development of curcumin anti-inflammatory preparations.
| S-EPMC8572027 | biostudies-literature
Project description:Alzheimer's disease (AD) is a lethal neurodegenerative disorder primarily affecting the aged population. The etiopathogenesis of AD, especially that of the sporadic type, remains elusive. The triggering receptor expressed on myeloid cells 2 (TREM2), a member of TREM immunoglobulin superfamily, plays a critical role in microglial physiology. Missense mutations in human TREM2 are determined as genetic risk factors associated with the development of sporadic AD. However, the roles of TREM2 in the pathogenesis of AD are still to be established. In this review, we outlined the influence of Trem2 on balance of pro- and anti-inflammatory microglial activations from a perspective of AD mouse model transcriptomics. On this basis, we further speculated the roles of TREM2 in different stages of AD, which may shed light to the development of TREM2-targeted strategy for the prevention and treatment of this neurodegenerative disorder.
| S-EPMC7913972 | biostudies-literature