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Aging: Oxidative Stress and Inflammation: New Target to Promote Healthy Longevity

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (30 October 2022) | Viewed by 25951

Special Issue Editor

Dr. Maria Grazia Bottone

E-Mail Website
Guest Editor
Laboratory of Cellular Biology and Neurobiology, Department of Biology and Biotecnology, University of Pavia, 9-27100 Pavia, Italy
Interests: cell death; brain tumors; cisplatin; new platinum compounds; microscopy; immunohistochemistry; cell cultures
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Aging refers to the progressive loss of the functionality of tissues and organs over time. It is a very complex phenomenon in which many physiological processes interact at multiple levels, playing an important role in the induction of cellular senescence. This process has received considerable attention in recent years because it could be considered as a potential target in the prevention and treatment of metabolic diseases such as diabetes and degenerative diseases such as Alzheimer's and cardiovascular diseases, and it has also been linked to age and prolonged health.

Older age is associated with a higher incidence of a variety of chronic disease states that share oxidative stress and inflammation, as well as the combination of genetic and lifestyle factors that can speed up or slow down the process.

As we age, our bodies' ability to function optimally decreases. There is a combination of genetic and lifestyle factors that can speed up or slow down the aging process. A number of chronic diseases are associated with older age: these include cardiovascular disease (CVD), diabetes, metabolic syndrome, and Alzheimer's disease. These diseases result in an exponential increase in the burden of disease on modern society compared to a few decades ago due to the longer life expectancy. The World Health Organization states that from 2015 to 2050, the percentage of the world population over 60 will increase from 12% to 22% [1]. Considering that prevailing research in the field of age-associated diseases considers the sixth decade of life a risk factor for the rapid progression and onset of age-associated diseases, the disease burden will almost double over the next 35 years. It is therefore crucial not only to clarify the causes and progression of these chronic conditions but also to actively research and study potential preventive therapies that can slow down the processes that contribute to physiological aging.

Understanding the cellular mechanisms of oxidative stress and neuroinflammation and the genetics underlying aging can become a powerful tool for delaying or preventing the development of many diseases or even rejuvenating tissues and organisms.

Dr. Maria Grazia Bottone
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • brain diseases
  • aging
  • oxidative stress
  • inflammaging
  • metabolic syndromes
  • antioxidants
  • age-related diseases
  • prevention of age-related diseases

Published Papers (7 papers)

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Research

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17 pages, 3931 KiB  
Article
Voghera Sweet Pepper: A Potential Ally against Oxidative Stress and Aging
by Federica Gola, Ludovica Gaiaschi, Elisa Roda, Fabrizio De Luca, Federica Ferulli, Riccardo Vicini, Paola Rossi and Maria Grazia Bottone
Int. J. Mol. Sci. 2023, 24(4), 3782; https://doi.org/10.3390/ijms24043782 - 14 Feb 2023
Viewed by 1571
Abstract
In the present study, the potential functional properties of the extracts from the edible part of Capsicum annuum L. var. Peperone di Voghera (VP) were studied. The phytochemical analysis revealed a high amount of ascorbic acid, paralleled by a low carotenoid content. Normal [...] Read more.
In the present study, the potential functional properties of the extracts from the edible part of Capsicum annuum L. var. Peperone di Voghera (VP) were studied. The phytochemical analysis revealed a high amount of ascorbic acid, paralleled by a low carotenoid content. Normal human diploid fibroblasts (NHDF) were chosen as the in vitro model models to investigate the effects of the VP extract on oxidative stress and aging pathways. The extract of Carmagnola pepper (CP), another important Italian variety, was used as the reference vegetable. The cytotoxicity evaluation was performed firstly, using a 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay, while the VP potential antioxidant and antiaging activity was investigated by immunofluorescence staining focusing on specifically selected proteins. The MTT data revealed the highest cell viability at a concentration of up to 1 mg/mL. The immunocytochemical analyses highlighted an increased expression of transcription factors and enzymes involved in redox homeostasis (Nrf2, SOD2, catalase), improved mitochondrial functionality, and the up-regulation of the longevity gene SIRT1. The present results supported the functional role of the VP pepper ecotype, suggesting a feasible use of its derived products as valuable food supplements. Full article
(This article belongs to the Special Issue Aging: Oxidative Stress and Inflammation: New Target to Promote Healthy Longevity)
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16 pages, 1200 KiB  
Article
Immunosenescence in Aging-Related Vascular Dysfunction
by Anna Tylutka, Barbara Morawin, Edyta Wawrzyniak-Gramacka, Eryk Wacka, Wiktoria Nowicka, Jaroslaw Hiczkiewicz and Agnieszka Zembron-Lacny
Int. J. Mol. Sci. 2022, 23(21), 13269; https://doi.org/10.3390/ijms232113269 - 31 Oct 2022
Cited by 3 | Viewed by 1602
Abstract
The immunosenescence-related disproportion in T lymphocytes may have important consequences for endothelial dysfunction, which is a key event in vascular aging. The study was designed to assess the prognostic values of the inflammatory-immune profile to better predict and prevent vascular diseases associated with [...] Read more.
The immunosenescence-related disproportion in T lymphocytes may have important consequences for endothelial dysfunction, which is a key event in vascular aging. The study was designed to assess the prognostic values of the inflammatory-immune profile to better predict and prevent vascular diseases associated with old age. Eighty individuals aged 70.9 ± 5.3 years were allocated to a low- (LGI) or high-grade inflammation (HGI) group based on CRP (<3 or ≥3 mg/L) as a conventional risk marker of cardiovascular diseases. Significant changes in inflammatory and endothelium-specific variables IL-1β, IL-6, TNFα, oxLDL, H2O2, NO, 3-nitrotyrosine, and endothelial progenitor cells (OR 7.61, 95% CI 2.56–29.05, p < 0.0001), confirmed their interplay in vascular inflammation. The flow-cytometry analysis demonstrated a high disproportion in T lymphocytes CD4+ and CD8+ between LGI and HGI groups. CRP was <3 mg/mL for the CD4/CD8 ratio within the reference values ≥ 1 or ≤2.5, unlike for the CD4/CD8 ratio < 1 and >2.5. The odds ratios for the distribution of CD4+ (OR 5.98, 95% CI 0.001–0.008, p < 0.001), CD8+ (OR 0.23, 95% CI 0.08–0.59, p < 0.01), and CD8CD45RO+ T naïve cells (OR 0.27, 95% CI 0.097–0.695, p < 0.01) and CD4/CD8 (OR 5.69, 95% CI 2.07–17.32, p < 0.001) indicated a potential diagnostic value of T lymphocytes for clinical prognosis in aging-related vascular dysfunction. Full article
(This article belongs to the Special Issue Aging: Oxidative Stress and Inflammation: New Target to Promote Healthy Longevity)
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17 pages, 3108 KiB  
Article
Expression of Polyamine Oxidase in Fibroblasts Induces MMP-1 and Decreases the Integrity of Extracellular Matrix
by Hae Dong Jeong, Jin Hyung Kim, Go Eun Kwon and Seung-Taek Lee
Int. J. Mol. Sci. 2022, 23(18), 10487; https://doi.org/10.3390/ijms231810487 - 10 Sep 2022
Cited by 4 | Viewed by 1805
Abstract
Polyamine oxidase (PAOX) (N1-acetylpolyamine oxidase) is a major enzyme in the polyamine catabolism pathway that generates hydrogen peroxide. Hydrogen peroxide plays a crucial role in skin aging via extracellular matrix (ECM) degradation by increasing the matrix metalloproteinase-1 (MMP-1) levels. We [...] Read more.
Polyamine oxidase (PAOX) (N1-acetylpolyamine oxidase) is a major enzyme in the polyamine catabolism pathway that generates hydrogen peroxide. Hydrogen peroxide plays a crucial role in skin aging via extracellular matrix (ECM) degradation by increasing the matrix metalloproteinase-1 (MMP-1) levels. We analyzed the integrity of the ECM in foreskin fibroblasts using PAOX expression. PAOX increased the MMP-1 secretion and type Ι collagen degradation in 2D and 3D cultures of fibroblasts, respectively. Similarly, PAOX overexpression increased the messenger ribonucleic acid (mRNA) level of MMP-1. PAOX expression induced polyamine catabolism, decreased the spermine levels, and increased the putrescine levels. However, the exogenous polyamine treatment did not change the MMP-1 and type I collagen levels as much as PAOX expression. PAOX expression increased the reactive oxygen species (ROS) production in fibroblasts, and exogenous hydrogen peroxide increased both the ROS production and MMP-1 secretion. Furthermore, N-acetylcysteine, an antioxidant, reversed the PAOX-induced ROS production and MMP-1 secretion. PAOX induced the signaling pathways that activate activator protein-1 (AP-1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), which are important transcription factors for MMP-1 transactivation. We concluded that PAOX increased the ROS levels in fibroblasts, leading to an increase in MMP-1 expression. Therefore, we propose that PAOX is a potential target molecule in protecting the ECM integrity. Full article
(This article belongs to the Special Issue Aging: Oxidative Stress and Inflammation: New Target to Promote Healthy Longevity)
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Review

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22 pages, 1972 KiB  
Review
MicroRNAs as the Sentinels of Redox and Hypertrophic Signalling
by Filip Kolodziej, Brian McDonagh, Nicole Burns and Katarzyna Goljanek-Whysall
Int. J. Mol. Sci. 2022, 23(23), 14716; https://doi.org/10.3390/ijms232314716 - 25 Nov 2022
Cited by 2 | Viewed by 2096
Abstract
Oxidative stress and inflammation are associated with skeletal muscle function decline with ageing or disease or inadequate exercise and/or poor diet. Paradoxically, reactive oxygen species and inflammatory cytokines are key for mounting the muscular and systemic adaptive responses to endurance and resistance exercise. [...] Read more.
Oxidative stress and inflammation are associated with skeletal muscle function decline with ageing or disease or inadequate exercise and/or poor diet. Paradoxically, reactive oxygen species and inflammatory cytokines are key for mounting the muscular and systemic adaptive responses to endurance and resistance exercise. Both ageing and lifestyle-related metabolic dysfunction are strongly linked to exercise redox and hypertrophic insensitivity. The adaptive inability and consequent exercise intolerance may discourage people from physical training resulting in a vicious cycle of under-exercising, energy surplus, chronic mitochondrial stress, accelerated functional decline and increased susceptibility to serious diseases. Skeletal muscles are malleable and dynamic organs, rewiring their metabolism depending on the metabolic or mechanical stress resulting in a specific phenotype. Endogenous RNA silencing molecules, microRNAs, are regulators of these metabolic/phenotypic shifts in skeletal muscles. Skeletal muscle microRNA profiles at baseline and in response to exercise have been observed to differ between adult and older people, as well as trained vs. sedentary individuals. Likewise, the circulating microRNA blueprint varies based on age and training status. Therefore, microRNAs emerge as key regulators of metabolic health/capacity and hormetic adaptability. In this narrative review, we summarise the literature exploring the links between microRNAs and skeletal muscle, as well as systemic adaptation to exercise. We expand a mathematical model of microRNA burst during adaptation to exercise through supporting data from the literature. We describe a potential link between the microRNA-dependent regulation of redox-signalling sensitivity and the ability to mount a hypertrophic response to exercise or nutritional cues. We propose a hypothetical model of endurance exercise-induced microRNA “memory cloud” responsible for establishing a landscape conducive to aerobic as well as anabolic adaptation. We suggest that regular aerobic exercise, complimented by a healthy diet, in addition to promoting mitochondrial health and hypertrophic/insulin sensitivity, may also suppress the glycolytic phenotype and mTOR signalling through miRNAs which in turn promote systemic metabolic health. Full article
(This article belongs to the Special Issue Aging: Oxidative Stress and Inflammation: New Target to Promote Healthy Longevity)
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36 pages, 1702 KiB  
Review
Effect of Physical Activity/Exercise on Oxidative Stress and Inflammation in Muscle and Vascular Aging
by Mariam El Assar, Alejandro Álvarez-Bustos, Patricia Sosa, Javier Angulo and Leocadio Rodríguez-Mañas
Int. J. Mol. Sci. 2022, 23(15), 8713; https://doi.org/10.3390/ijms23158713 - 05 Aug 2022
Cited by 53 | Viewed by 10967
Abstract
Functional status is considered the main determinant of healthy aging. Impairment in skeletal muscle and the cardiovascular system, two interrelated systems, results in compromised functional status in aging. Increased oxidative stress and inflammation in older subjects constitute the background for skeletal muscle and [...] Read more.
Functional status is considered the main determinant of healthy aging. Impairment in skeletal muscle and the cardiovascular system, two interrelated systems, results in compromised functional status in aging. Increased oxidative stress and inflammation in older subjects constitute the background for skeletal muscle and cardiovascular system alterations. Aged skeletal muscle mass and strength impairment is related to anabolic resistance, mitochondrial dysfunction, increased oxidative stress and inflammation as well as a reduced antioxidant response and myokine profile. Arterial stiffness and endothelial function stand out as the main cardiovascular alterations related to aging, where increased systemic and vascular oxidative stress and inflammation play a key role. Physical activity and exercise training arise as modifiable determinants of functional outcomes in older persons. Exercise enhances antioxidant response, decreases age-related oxidative stress and pro-inflammatory signals, and promotes the activation of anabolic and mitochondrial biogenesis pathways in skeletal muscle. Additionally, exercise improves endothelial function and arterial stiffness by reducing inflammatory and oxidative damage signaling in vascular tissue together with an increase in antioxidant enzymes and nitric oxide availability, globally promoting functional performance and healthy aging. This review focuses on the role of oxidative stress and inflammation in aged musculoskeletal and vascular systems and how physical activity/exercise influences functional status in the elderly. Full article
(This article belongs to the Special Issue Aging: Oxidative Stress and Inflammation: New Target to Promote Healthy Longevity)
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19 pages, 965 KiB  
Review
Hypoxia in Aging and Aging-Related Diseases: Mechanism and Therapeutic Strategies
by Yaqin Wei, Sergio Giunta and Shijin Xia
Int. J. Mol. Sci. 2022, 23(15), 8165; https://doi.org/10.3390/ijms23158165 - 25 Jul 2022
Cited by 16 | Viewed by 4438
Abstract
As the global aging process continues to lengthen, aging-related diseases (e.g., chronic obstructive pulmonary disease (COPD), heart failure) continue to plague the elderly population. Aging is a complex biological process involving multiple tissues and organs and is involved in the development and progression [...] Read more.
As the global aging process continues to lengthen, aging-related diseases (e.g., chronic obstructive pulmonary disease (COPD), heart failure) continue to plague the elderly population. Aging is a complex biological process involving multiple tissues and organs and is involved in the development and progression of multiple aging-related diseases. At the same time, some of these aging-related diseases are often accompanied by hypoxia, chronic inflammation, oxidative stress, and the increased secretion of the senescence-associated secretory phenotype (SASP). Hypoxia seems to play an important role in the process of inflammation and aging, but is often neglected in advanced clinical research studies. Therefore, we have attempted to elucidate the role played by different degrees and types of hypoxia in aging and aging-related diseases and their possible pathways, and propose rational treatment options based on such mechanisms for reference. Full article
(This article belongs to the Special Issue Aging: Oxidative Stress and Inflammation: New Target to Promote Healthy Longevity)
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13 pages, 870 KiB  
Review
Mitochondrial Implications in Cardiovascular Aging and Diseases: The Specific Role of Mitochondrial Dynamics and Shifts
by Anastasia V. Poznyak, Tatiana V. Kirichenko, Evgeny E. Borisov, Nikolay K. Shakhpazyan, Andrey G. Kartuesov and Alexander N. Orekhov
Int. J. Mol. Sci. 2022, 23(6), 2951; https://doi.org/10.3390/ijms23062951 - 09 Mar 2022
Cited by 5 | Viewed by 2423
Abstract
Cardiovascular disease has been, and remains, one of the leading causes of death in the modern world. The elderly are a particularly vulnerable group. The aging of the body is inevitably accompanied by the aging of all its systems, and the cardiovascular system [...] Read more.
Cardiovascular disease has been, and remains, one of the leading causes of death in the modern world. The elderly are a particularly vulnerable group. The aging of the body is inevitably accompanied by the aging of all its systems, and the cardiovascular system is no exception. The aging of the cardiovascular system is a significant risk factor for the development of various diseases and pathologies, from atherosclerosis to ischemic stroke. Mitochondria, being the main supplier of energy necessary for the normal functioning of cells, play an important role in the proper functioning of the cardiovascular system. The functioning of each individual cell and the organism as a whole depends on their number, structure, and performance, as well as the correct operation of the system in removing non-functional mitochondria. In this review, we examine the role of mitochondria in the aging of the cardiovascular system, as well as in diseases (for example, atherosclerosis and ischemic stroke). We pay special attention to changes in mitochondrial dynamics since the shift in the balance between fission and fusion is one of the main factors associated with various cardiovascular pathologies. Full article
(This article belongs to the Special Issue Aging: Oxidative Stress and Inflammation: New Target to Promote Healthy Longevity)
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