Ageing, Age-Related Cardiovascular Risk and the Beneficial Role of Natural Components Intake

Ageing, in a natural way, leads to the gradual worsening of the functional capacity of all systems and, eventually, to death. This process is strongly associated with higher metabolic and oxidative stress, low-grade inflammation, accumulation of DNA mutations and increased levels of related damage. Detrimental changes that accumulate in body cells and tissues with time raise the vulnerability to environmental challenges and enhance the risk of major chronic diseases and mortality. There are several theses concerning the mechanisms of ageing: genetic, free radical telomerase, mitochondrial decline, metabolic damage, cellular senescence, neuroendocrine theory, Hay-flick limit and membrane theories, cellular death as well as the accumulation of toxic and non-toxic garbage. Moreover, ageing is associated with structural changes within the myocardium, cardiac conduction system, the endocardium as well as the vasculature. With time, the cardiac structures lose elasticity, and fibrotic changes occur in the heart valves. Ageing is also associated with a higher risk of atherosclerosis. The results of studies suggest that some natural compounds may slow down this process and protect against age-related diseases. Animal studies imply that some of them may prolong the lifespan; however, this trend is not so obvious in humans.

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The Roles of the Gut Microbiota and Chronic Low-Grade Inflammation in Older Adults With Frailty

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.675414 ◽

2021 ◽

Vol 11 ◽

Author(s):

YuShuang Xu ◽

XiangJie Liu ◽

XiaoXia Liu ◽

Di Chen ◽

MengMeng Wang ◽

...

Keyword(s):

Older Adults ◽

Gut Microbiota ◽

Chronic Inflammation ◽

Healthy Aging ◽

Low Grade ◽

Age Related ◽

Composition Structure ◽

Low Grade Inflammation

Frailty is a major public issue that affects the physical health and quality of life of older adults, especially as the population ages. Chronic low-grade inflammation has been speculated to accelerate the aging process as well as the development of age-related diseases such as frailty. Intestinal homeostasis plays a crucial role in healthy aging. The interaction between the microbiome and the host regulates the inflammatory response. Emerging evidence indicates that in older adults with frailty, the diversity and composition structure of gut microbiota are altered. Age-associated changes in gut microbiota composition and in their metabolites contribute to increased gut permeability and imbalances in immune function. In this review, we aim to: identify gut microbiota changes in the aging and frail populations; summarize the role of chronic low-grade inflammation in the development of frailty; and outline how gut microbiota may be related to the pathogenesis of frailty, more specifically, in the regulation of gut-derived chronic inflammation. Although additional research is needed, the regulation of gut microbiota may represent a safe, easy, and inexpensive intervention to counteract the chronic inflammation leading to frailty.

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The Role of Oxidative Stress and Inflammation in Cardiovascular Aging

BioMed Research International ◽

10.1155/2014/615312 ◽

2014 ◽

Vol 2014 ◽

pp. 1-13 ◽

Cited By ~ 92

Author(s):

Junzhen Wu ◽

Shijin Xia ◽

Bill Kalionis ◽

Wenbin Wan ◽

Tao Sun

Keyword(s):

Oxidative Stress ◽

Cardiovascular Disease ◽

Ventricular Hypertrophy ◽

Left Ventricular ◽

Low Grade ◽

Oxygen Species ◽

Age Related ◽

Vascular Elasticity ◽

Low Grade Inflammation

Age is an independent risk factor of cardiovascular disease, even in the absence of other traditional factors. Emerging evidence in experimental animal and human models has emphasized a central role for two main mechanisms of age-related cardiovascular disease: oxidative stress and inflammation. Excess reactive oxygen species (ROS) and superoxide generated by oxidative stress and low-grade inflammation accompanying aging recapitulate age-related cardiovascular dysfunction, that is, left ventricular hypertrophy, fibrosis, and diastolic dysfunction in the heart as well as endothelial dysfunction, reduced vascular elasticity, and increased vascular stiffness. We describe the signaling involved in these two main mechanisms that include the factors NF-κB, JunD, p66Shc, and Nrf2. Potential therapeutic strategies to improve the cardiovascular function with aging are discussed, with a focus on calorie restriction, SIRT1, and resveratrol.

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Role of Metabolic Endotoxemia in Systemic Inflammation and Potential Interventions

Frontiers in Immunology ◽

10.3389/fimmu.2020.594150 ◽

2021 ◽

Vol 11 ◽

Author(s):

Shireen Mohammad ◽

Christoph Thiemermann

Keyword(s):

Systemic Inflammation ◽

Structural Changes ◽

Low Grade ◽

Dietary Interventions ◽

Toll Like Receptor 4 ◽

Alcoholic Fatty Liver ◽

Inflammatory Conditions ◽

Low Grade Inflammation ◽

Metabolic Endotoxemia

Diet-induced metabolic endotoxemia is an important factor in the development of many chronic diseases in animals and man. The gut epithelium is an efficient barrier that prevents the absorption of liposaccharide (LPS). Structural changes to the intestinal epithelium in response to dietary alterations allow LPS to enter the bloodstream, resulting in an increase in the plasma levels of LPS (termed metabolic endotoxemia). LPS activates Toll-like receptor-4 (TLR4) leading to the production of numerous pro-inflammatory cytokines and, hence, low-grade systemic inflammation. Thus, metabolic endotoxemia can lead to several chronic inflammatory conditions. Obesity, diabetes, and non-alcoholic fatty liver disease (NAFLD) can also cause an increase in gut permeability and potential pharmacological and dietary interventions could be used to reduce the chronic low-grade inflammation associated with endotoxemia.

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INVESTIGATING THE ROLE OF AHR IN MEDIATING SEX DIFFERENCES OF AGING MACROPHAGES

Innovation in Aging ◽

10.1093/geroni/igz038.3080 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S836-S836

Author(s):

Evelyn Navar ◽

Bérénice A Benayoun ◽

Nirmal Sampathkumar ◽

Jisoo Chae

Keyword(s):

Short Exposure ◽

Low Grade ◽

Rna Seq ◽

Phagocytosis Assay ◽

Short Exposure Time ◽

Aryl Hydrocarbon ◽

Age Related ◽

Low Grade Inflammation ◽

Phagocytosis Activity

Abstract “Inflamm-aging” describes a state of chronic low-grade inflammation which occurs with age in the absence of infection. This process is related to many chronic age-related diseases. Aryl hydrocarbon receptor (Ahr), is a transcription factor that is thought to decrease inflammation, and decrease of Ahr with aging only in females was previously observed in a macrophage RNA-seq with aging. Based on this, I hypothesized that 1) Ahr expression will decrease with age in female cells; and 2) phagocytic activity and Ahr expression in macrophages will increase when exposed to estrogens (E2). To test these hypotheses, Ahr signaling was quantified by RT-qPCR in aging male and female mice BMDMs, and in macrophages that were treated with E2. I also performed a phagocytosis assay on macrophages treated with E2. I found a significant downregulation of Ahr in old female BMDMs. Ahrr (Ahr Repressor) was significantly downregulated in both old female and males with aging. Arnt (Ahr Nuclear Translocator) did not significantly change with aging. The qPCR performed on the E2 treated cells showed no significant trend for Ahr regulation. Finally, the phagocytosis assay revealed an overall increase in phagocytosis activity in cells treated with estrogen. Our hypotheses were supported by data showing a decrease in Ahr expression with age and increase in phagocytosis activity in estrogen treated cells. The RT-qPCR results for the E2 treated cells did not support our hypothesis, but could stem from a relatively short exposure time for estrogen.

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Mitochondria, immunosenescence and inflammaging: a role for mitokines?

Seminars in Immunopathology ◽

10.1007/s00281-020-00813-0 ◽

2020 ◽

Vol 42 (5) ◽

pp. 607-617 ◽

Cited By ~ 4

Author(s):

Maria Conte ◽

Morena Martucci ◽

Antonio Chiariello ◽

Claudio Franceschi ◽

Stefano Salvioli

Keyword(s):

Immune Responses ◽

Acute Inflammation ◽

Current Knowledge ◽

Low Grade ◽

Mitochondrial Stress ◽

Age Related ◽

Metabolic Mechanism ◽

Anti Inflammatory ◽

Low Grade Inflammation

AbstractA global reshaping of the immune responses occurs with ageing, indicated as immunosenescence, where mitochondria and mitochondrial metabolism play an important role. However, much less is known about the role of mitochondrial stress response in this reshaping and in particular of the molecules induced by such response, collectively indicated as mitokines. In this review, we summarize the current knowledge on the role of mitokines in modulating immune response and inflammation focusing on GDF15, FGF21 and humanin and their possible involvement in the chronic age-related low-grade inflammation dubbed inflammaging. Although many aspects of their biology are still controversial, available data suggest that these mitokines have an anti-inflammatory role and increase with age. Therefore, we hypothesize that they can be considered part of an adaptive and integrated immune-metabolic mechanism activated by mitochondrial dysfunction that acts within the framework of a larger anti-inflammatory network aimed at controlling both acute inflammation and inflammaging.

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The Role of Diet, Micronutrients and the Gut Microbiota in Age-Related Macular Degeneration: New Perspectives from the Gut-Retina Axis

10.20944/preprints201810.0369.v1 ◽

2018 ◽

Author(s):

Emanuele Rinninella ◽

Maria Cristina Mele ◽

Nicolò Merendino ◽

Marco Cintoni ◽

Gaia Anselmi ◽

...

Keyword(s):

Gut Microbiota ◽

Macular Degeneration ◽

Potential Role ◽

Dietary Habits ◽

Age Related Macular Degeneration ◽

Low Grade ◽

Age Related ◽

The Impact ◽

Low Grade Inflammation

Age-related macular degeneration (AMD) is a complex multifactorial disease and the primary cause of legal and irreversible blindness among individuals aged >=65 years in developed countries. Globally, it affects 30-50 million individuals, with an estimated increase of approximately 200 million by 2020 and approximately 300 million by 2040. Currently, the neovascular form may be able to be treated with the use of anti-VEGF drugs, while no effective treatments are available for the dry form. Many observational studies, such as AREDS-1 and AREDS 2, have shown a potential role of micronutrient supplementation in lowering the risk of progression of the early stages of AMD. Recently, low-grade inflammation, sustained by dysbiosis and a leaky gut, has been shown to contribute to the development of AMD. Given the ascertained influence of the gut microbiota in systemic low-grade inflammation and its potential modulation by macro- and micro-nutrients, a potential role of diet in AMD has been proposed. This review discusses the role of the gut microbiota in the development of AMD. Using PubMed, Web of Science and Scopus, we searched for recent scientific evidence discussing the impact of dietary habits (high fat and high glucose or fructose diets), micronutrients (vitamins C, E, and D, zinc, beta-carotene, lutein and zeaxanthin) and omega-3 fatty acids on the modulation of the gut microbiota and their relationship with AMD risk and progression.

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The Role of Diet, Micronutrients and the Gut Microbiota in Age-Related Macular Degeneration: New Perspectives from the Gut–Retina Axis

Nutrients ◽

10.3390/nu10111677 ◽

2018 ◽

Vol 10 (11) ◽

pp. 1677 ◽

Cited By ~ 27

Author(s):

Emanuele Rinninella ◽

Maria Mele ◽

Nicolò Merendino ◽

Marco Cintoni ◽

Gaia Anselmi ◽

...

Keyword(s):

Gut Microbiota ◽

Macular Degeneration ◽

Potential Role ◽

Dietary Habits ◽

Age Related Macular Degeneration ◽

Low Grade ◽

Age Related ◽

The Impact ◽

Low Grade Inflammation

Age-related macular degeneration (AMD) is a complex multifactorial disease and the primary cause of legal and irreversible blindness among individuals aged ≥65 years in developed countries. Globally, it affects 30–50 million individuals, with an estimated increase of approximately 200 million by 2020 and approximately 300 million by 2040. Currently, the neovascular form may be able to be treated with the use of anti-VEGF drugs, while no effective treatments are available for the dry form. Many studies, such as the randomized controlled trials (RCTs) Age-Related Eye Disease Study (AREDS) and AREDS 2, have shown a potential role of micronutrient supplementation in lowering the risk of progression of the early stages of AMD. Recently, low-grade inflammation, sustained by dysbiosis and a leaky gut, has been shown to contribute to the development of AMD. Given the ascertained influence of the gut microbiota in systemic low-grade inflammation and its potential modulation by macro- and micro-nutrients, a potential role of diet in AMD has been proposed. This review discusses the role of the gut microbiota in the development of AMD. Using PubMed, Web of Science and Scopus, we searched for recent scientific evidence discussing the impact of dietary habits (high-fat and high-glucose or -fructose diets), micronutrients (vitamins C, E, and D, zinc, beta-carotene, lutein and zeaxanthin) and omega-3 fatty acids on the modulation of the gut microbiota and their relationship with AMD risk and progression.

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Mitochondrial (Dys) Function in Inflammaging: Do MitomiRs Influence the Energetic, Oxidative, and Inflammatory Status of Senescent Cells?

Mediators of Inflammation ◽

10.1155/2017/2309034 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11 ◽

Cited By ~ 16

Author(s):

Angelica Giuliani ◽

Francesco Prattichizzo ◽

Luigina Micolucci ◽

Antonio Ceriello ◽

Antonio Domenico Procopio ◽

...

Keyword(s):

Mitochondrial Gene ◽

Low Grade ◽

Master Regulators ◽

Inflammatory Status ◽

Age Related ◽

Secretory Phenotype ◽

And Function ◽

Low Grade Inflammation ◽

Proinflammatory Factors

A relevant feature of aging is chronic low-grade inflammation, termed inflammaging, a key process promoting the development of all major age-related diseases. Senescent cells can acquire the senescence-associated (SA) secretory phenotype (SASP), characterized by the secretion of proinflammatory factors fuelling inflammaging. Cellular senescence is also accompanied by a deep reshaping of microRNA expression and by the modulation of mitochondria activity, both master regulators of the SASP. Here, we synthesize novel findings regarding the role of mitochondria in the SASP and in the inflammaging process and propose a network linking nuclear-encoded SA-miRNAs to mitochondrial gene regulation and function in aging cells. In this conceptual structure, SA-miRNAs can translocate to mitochondria (SA-mitomiRs) and may affect the energetic, oxidative, and inflammatory status of senescent cells. We discuss the potential role of several of SA-mitomiRs (i.e., let-7b, miR-1, miR-130a-3p, miR-133a, miR-146a-5p, miR-181c-5p, and miR-378-5p), using miR-146a as a proof-of-principle model. Finally, we propose a comprehensive, metabolic, and epigenetic view of the senescence process, in order to amplify the range of possible approaches to target inflammaging, with the ultimate goal of decelerating the aging rate, postponing or blunting the development of age-related diseases.

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The Role of Epicardial Adipose Tissue Lymphocytes in Low-Grade Inflammation and Coronary Artery Disease

Diabetes ◽

10.2337/db18-469-p ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 469-P

Author(s):

MILOS MRAZ ◽

ANNA CINKAJZLOVA ◽

ZDENA LACINOVÁ ◽

JANA KLOUCKOVA ◽

HELENA KRATOCHVILOVA ◽

...

Keyword(s):

Coronary Artery Disease ◽

Adipose Tissue ◽

Coronary Artery ◽

Epicardial Adipose Tissue ◽

Low Grade ◽

Artery Disease ◽

Low Grade Inflammation

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Adipose tissue inflammation and metabolic dysfunction: a clinical perspective

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2013-0032 ◽

2013 ◽

Vol 15 (1) ◽

Cited By ~ 2

Author(s):

Charmaine S. Tam ◽

Leanne M. Redman

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Low Grade ◽

Metabolic Dysfunction ◽

Adipose Tissue Inflammation ◽

Tissue Inflammation ◽

Proinflammatory Mediators ◽

Low Grade Inflammation

AbstractObesity is characterized by a state of chronic low-grade inflammation due to increased immune cells, specifically infiltrated macrophages into adipose tissue, which in turn secrete a range of proinflammatory mediators. This nonselective low-grade inflammation of adipose tissue is systemic in nature and can impair insulin signaling pathways, thus, increasing the risk of developing insulin resistance and type 2 diabetes. The aim of this review is to provide an update on clinical studies examining the role of adipose tissue in the development of obesity-associated complications in humans. We will discuss adipose tissue inflammation during different scenarios of energy imbalance and metabolic dysfunction including obesity and overfeeding, weight loss by calorie restriction or bariatric surgery, and conditions of insulin resistance (diabetes, polycystic ovarian syndrome).

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