Long Noncoding Competing Endogenous RNA Networks in Age-Associated Cardiovascular Diseases

Cardiovascular diseases (CVDs) are the most serious health problem in the world, displaying high rates of morbidity and mortality. One of the main risk factors for CVDs is age. Indeed, several mechanisms are at play during aging, determining the functional decline of the cardiovascular system. Aging cells and tissues are characterized by diminished autophagy, causing the accumulation of damaged proteins and mitochondria, as well as by increased levels of oxidative stress, apoptosis, senescence and inflammation. These processes can induce a rapid deterioration of cellular quality-control systems. However, the molecular mechanisms of age-associated CVDs are only partially known, hampering the development of novel therapeutic strategies. Evidence has emerged indicating that noncoding RNAs (ncRNAs), such as long ncRNAs (lncRNAs) and micro RNAs (miRNAs), are implicated in most patho-physiological mechanisms. Specifically, lncRNAs can bind miRNAs and act as competing endogenous-RNAs (ceRNAs), therefore modulating the levels of the mRNAs targeted by the sponged miRNA. These complex lncRNA/miRNA/mRNA networks, by regulating autophagy, apoptosis, necrosis, senescence and inflammation, play a crucial role in the development of age-dependent CVDs. In this review, the emerging knowledge on lncRNA/miRNA/mRNA networks will be summarized and the way in which they influence age-related CVDs development will be discussed.

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The Senescence-Associated Secretory Phenotype (SASP) in the Challenging Future of Cancer Therapy and Age-Related Diseases

Biology ◽

10.3390/biology9120485 ◽

2020 ◽

Vol 9 (12) ◽

pp. 485

Author(s):

Lorenzo Cuollo ◽

Fabrizio Antonangeli ◽

Angela Santoni ◽

Alessandra Soriani

Keyword(s):

Cancer Therapy ◽

Molecular Mechanisms ◽

Therapeutic Strategies ◽

Senescent Cell ◽

Pharmacological Intervention ◽

Tissue Microenvironment ◽

Age Related ◽

Secretory Phenotype ◽

Novel Therapeutic Strategies ◽

Novel Therapeutic

Cellular senescence represents a robust tumor-protecting mechanism that halts the proliferation of stressed or premalignant cells. However, this state of stable proliferative arrest is accompanied by the Senescence-Associated Secretory Phenotype (SASP), which entails the copious secretion of proinflammatory signals in the tissue microenvironment and contributes to age-related conditions, including, paradoxically, cancer. Novel therapeutic strategies aim at eliminating senescent cells with the use of senolytics or abolishing the SASP without killing the senescent cell with the use of the so-called “senomorphics”. In addition, recent works demonstrate the possibility of modifying the composition of the secretome by genetic or pharmacological intervention. The purpose is not to renounce the potent immunostimulatory nature of SASP, but rather learning to modulate it for combating cancer and other age-related diseases. This review describes the main molecular mechanisms regulating the SASP and reports the evidence of the feasibility of abrogating or modulating the SASP, discussing the possible implications of both strategies.

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Comprehensive transcriptional profiling of aging porcine liver

PeerJ ◽

10.7717/peerj.6949 ◽

2019 ◽

Vol 7 ◽

pp. e6949 ◽

Cited By ~ 1

Author(s):

Jianning Chen ◽

Qin Zou ◽

Daojun Lv ◽

Muhammad Ali Raza ◽

Xue Wang ◽

...

Keyword(s):

Human Liver ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Genomic Structure ◽

Circular Rnas ◽

Transcriptional Level ◽

Porcine Liver ◽

Age Related ◽

Micro Rnas ◽

Model Animal

Background Aging is a major risk factor for the development of many diseases, and the liver, as the most important metabolic organ, is significantly affected by aging. It has been shown that the liver weight tends to increase in rodents and decrease in humans with age. Pigs have a genomic structure, with physiological as well as biochemical features that are similar to those of humans, and have therefore been used as a valuable model for studying human diseases. The molecular mechanisms of the liver aging of large mammals on a comprehensive transcriptional level remain poorly understood. The pig is an ideal model animal to clearly and fully understand the molecular mechanism underlying human liver aging. Methods In this study, four healthy female Yana pigs (an indigenous Chinese breed) were investigated: two young sows (180-days-old) and two old sows (8-years-old). High throughput RNA sequencing was performed to evaluate the expression profiles of messenger RNA, long non-coding RNAs, micro RNAs, and circular RNAs during the porcine liver aging process. Gene Ontology (GO) analysis was performed to investigate the biological functions of age-related genes. Results A number of age-related genes were identified in the porcine liver. GO annotation showed that up-regulated genes were mainly related to immune response, while the down-regulated genes were mainly related to metabolism. Moreover, several lncRNAs and their target genes were also found to be differentially expressed during liver aging. In addition, the multi-group cooperative control relationships and constructed circRNA-miRNA co-expression networks were assessed during liver aging. Conclusions Numerous age-related genes were identified and circRNA-miRNA co-expression networks that are active during porcine liver aging were constructed. These findings contribute to the understanding of the transcriptional foundations of liver aging and also provide further references that clarify human liver aging at the molecular level.

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Molecular mechanisms of life- and health-span extension: role of calorie restriction and exercise intervention

Applied Physiology Nutrition and Metabolism ◽

10.1139/h07-085 ◽

2007 ◽

Vol 32 (5) ◽

pp. 954-966 ◽

Cited By ~ 49

Author(s):

Christy S. Carter ◽

Tim Hofer ◽

Arnold Y. Seo ◽

Christian Leeuwenburgh

Keyword(s):

Life Span ◽

Calorie Restriction ◽

Aging Process ◽

Molecular Mechanisms ◽

Geriatric Medicine ◽

Functional Decline ◽

Intervention Strategies ◽

Health Span ◽

Structural Deterioration ◽

Age Related

The aging process results in a gradual and progressive structural deterioration of biomolecular and cellular compartments and is associated with many pathological conditions, including cardiovascular disease, stroke, Alzheimer’s disease, osteoporosis, sarcopenia, and liver dysfunction. Concomitantly, each of these conditions is associated with progressive functional decline, loss of independence, and ultimately disability. Because disabled individuals require care in outpatient or home care settings, and in light of the social, emotional, and fiscal burden associated with caring for an ever-increasing elderly population, research in geriatric medicine has recently focused on the biological mechanisms that are involved in the progression towards functional decline and disability to better design treatment and intervention strategies. Although not completely understood, the mechanisms underlying the aging process may partly involve inflammatory processes, oxidative damage, mitochondrial dysfunction, and apoptotic tissue degeneration. These hypotheses are based on epidemiological evidence and data from animal models of aging, as well as interventional studies. Findings from these studies have identified possible strategies to decrease the incidence of age-related diseases and delay the aging process. For example, lifelong exercise is known to extend mean life-span, whereas calorie restriction (CR) increases both mean and maximum life-span in a variety of species. Optimal application of these intervention strategies in the elderly may positively affect health-related outcomes and possibly longevity. Therefore, the scope of this article is to (i) provide an interpretation of various theories of aging from a “health-span” perspective; (ii) describe interventional testing in animals (CR and exercise); and (iii) provide a translational interpretation of these data.

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Thrombospondin-1 in maladaptive aging responses: a concept whose time has come

AJP Cell Physiology ◽

10.1152/ajpcell.00089.2020 ◽

2020 ◽

Vol 319 (1) ◽

pp. C45-C63

Author(s):

Jeffrey S. Isenberg ◽

David D. Roberts

Keyword(s):

Molecular Mechanisms ◽

Synapse Formation ◽

Genotoxic Stress ◽

Cell Types ◽

Cellular Tissue ◽

Therapeutic Agents ◽

Age Related ◽

Organ Systems ◽

Age Dependent ◽

Thrombospondin 1

Numerous age-dependent alterations at the molecular, cellular, tissue and organ systems levels underlie the pathophysiology of aging. Herein, the focus is upon the secreted protein thrombospondin-1 (TSP1) as a promoter of aging and age-related diseases. TSP1 has several physiological functions in youth, including promoting neural synapse formation, mediating responses to ischemic and genotoxic stress, minimizing hemorrhage, limiting angiogenesis, and supporting wound healing. These acute functions of TSP1 generally require only transient expression of the protein. However, accumulating basic and clinical data reinforce the view that chronic diseases of aging are associated with accumulation of TSP1 in the extracellular matrix, which is a significant maladaptive contributor to the aging process. Identification of the relevant cell types that chronically produce and respond to TSP1 and the molecular mechanisms that mediate the resulting maladaptive responses could direct the development of therapeutic agents to delay or revert age-associated maladies.

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The GH/IGF1 axis and signaling pathways in the muscle and bone: mechanisms underlying age-related skeletal muscle wasting and osteoporosis

Journal of Endocrinology ◽

10.1677/joe-09-0431 ◽

2010 ◽

Vol 205 (3) ◽

pp. 201-210 ◽

Cited By ~ 188

Author(s):

Sebastio Perrini ◽

Luigi Laviola ◽

Marcos C Carreira ◽

Angelo Cignarelli ◽

Annalisa Natalicchio ◽

...

Keyword(s):

Skeletal Muscle ◽

Molecular Mechanisms ◽

Signs And Symptoms ◽

Well Being ◽

Serum Levels ◽

Normal Range ◽

Gh Secretion ◽

Skeletal Muscle Wasting ◽

Age Related ◽

Age Dependent

The widespread increase in life expectancy is accompanied by an increased prevalence of features of physical frailty. Signs and symptoms may include sarcopenia and osteopenia, reduced exercise capacity, and diminished sense of well-being. The pathogenesis of age-associated sarcopenia and osteopenia is multifactorial, and hormonal decline may be a contributing factor. Aging is associated with a progressive decrease in GH secretion, and more than 30% of elderly people have circulating IGF1 levels below the normal range found in the young. GH acts directly on target tissues, including skeletal muscle and bone among many others, but many effects are mediated indirectly by circulating (liver-derived) or locally produced IGF1. Aging is also associated with reduced insulin sensitivity which, in turn, may contribute to the impairment of IGF1 action. Recent experimental evidence suggests that besides the age-dependent decline in GH and IGF1 serum levels, the dysregulation of GH and IGF1 actions due to impairment of the post-receptor signaling machinery may contribute to the loss of muscle mass and osteopenia. This article will focus on the molecular mechanisms of impaired GH and IGF1 signaling and action in aging, and their role in the pathogenesis of sarcopenia and osteoporosis.

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The Role of Oxidative Stress in Cardiovascular Aging and Cardiovascular Diseases

Life ◽

10.3390/life11010060 ◽

2021 ◽

Vol 11 (1) ◽

pp. 60

Author(s):

Carmine Izzo ◽

Paolo Vitillo ◽

Paola Di Pietro ◽

Valeria Visco ◽

Andrea Strianese ◽

...

Keyword(s):

Oxidative Stress ◽

Cardiovascular Diseases ◽

Molecular Mechanisms ◽

Stress Theory ◽

Age Related ◽

Theory Of Aging ◽

Cardiovascular Aging ◽

Primary Risk Factor ◽

Structure And Functions

Aging can be seen as process characterized by accumulation of oxidative stress induced damage. Oxidative stress derives from different endogenous and exogenous processes, all of which ultimately lead to progressive loss in tissue and organ structure and functions. The oxidative stress theory of aging expresses itself in age-related diseases. Aging is in fact a primary risk factor for many diseases and in particular for cardiovascular diseases and its derived morbidity and mortality. Here we highlight the role of oxidative stress in age-related cardiovascular aging and diseases. We take into consideration the molecular mechanisms, the structural and functional alterations, and the diseases accompanied to the cardiovascular aging process.

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MECHANISMS OF BRAIN REJUVENATION

Innovation in Aging ◽

10.1093/geroni/igz038.2177 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S587-S587

Author(s):

Saul Villeda

Keyword(s):

Molecular Mechanisms ◽

Aging Brain ◽

Aging Effects ◽

Effective Strategies ◽

Mechanistic Insight ◽

Age Related ◽

Age Dependent ◽

Cognitive Faculties ◽

Insight Into ◽

Aging Factors

Abstract A growing body of work has shown that systemic manipulations, such as heterochronic parabiosis and young blood administration, can partially reverse age-related cellular impairments and loss of cognitive faculties in the aged brain. These studies have revealed an age-dependent bi-directionality in the influence of the systemic environment indicating anti-aging factors in young blood elicit rejuvenation while pro-aging factors in old blood drive aging. It has been proposed that introducing anti-aging factors or mitigating the effect of pro-aging factors may provide effective strategies to rejuvenate aging phenotypes. Despite this potential, much is unknown as to the systemic and molecular mechanisms regulating anti-aging and pro-aging effects of blood-borne factors. I will discuss work from my research group that begins to provide mechanistic insight into the systemic and molecular drivers promoting rejuvenation in the aging brain.

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Exosomes and Micro-RNAs in Aging Process

Biomedicines ◽

10.3390/biomedicines9080968 ◽

2021 ◽

Vol 9 (8) ◽

pp. 968

Author(s):

Yousra Hamdan ◽

Loubna Mazini ◽

Gabriel Malka

Keyword(s):

Messenger Rna ◽

Molecular Mechanisms ◽

Therapeutic Potential ◽

Biological Fluids ◽

Cell Types ◽

Exosome Biogenesis ◽

Age Related ◽

Micro Rnas ◽

Underlying Mechanisms ◽

Almost All

Exosomes are the main actors of intercellular communications and have gained great interest in the new cell-free regenerative medicine. These nanoparticles are secreted by almost all cell types and contain lipids, cytokines, growth factors, messenger RNA, and different non-coding RNA, especially micro-RNAs (mi-RNAs). Exosomes’ cargo is released in the neighboring microenvironment but is also expected to act on distant tissues or organs. Different biological processes such as cell development, growth and repair, senescence, migration, immunomodulation, and aging, among others, are mediated by exosomes and principally exosome-derived mi-RNAs. Moreover, their therapeutic potential has been proved and reinforced by their use as biomarkers for disease diagnostics and progression. Evidence has increasingly shown that exosome-derived mi-RNAs are key regulators of age-related diseases, and their involvement in longevity is becoming a promising issue. For instance, mi-RNAs such as mi-RNA-21, mi-RNA-29, and mi-RNA-34 modulate tissue functionality and regeneration by targeting different tissues and involving different pathways but might also interfere with long life expectancy. Human mi-RNAs profiling is effectively related to the biological fluids that are reported differently between young and old individuals. However, their underlying mechanisms modulating cell senescence and aging are still not fully understood, and little was reported on the involvement of mi-RNAs in cell or tissue longevity. In this review, we summarize exosome biogenesis and mi-RNA synthesis and loading mechanism into exosomes’ cargo. Additionally, we highlight the molecular mechanisms of exosomes and exosome-derived mi-RNA regulation in the different aging processes.

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Chondrocyte Aging: The Molecular Determinants and Therapeutic Opportunities

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.625497 ◽

2021 ◽

Vol 9 ◽

Author(s):

Thamil Selvee Ramasamy ◽

Yong Mei Yee ◽

Ilyas M. Khan

Keyword(s):

Molecular Mechanisms ◽

Articular Chondrocytes ◽

Functional Decline ◽

Cellular Aging ◽

Joint Degeneration ◽

Complex Interplay ◽

Regenerative Capacity ◽

Progressive Decline ◽

Age Related ◽

Molecular Determinants

Osteoarthritis (OA) is a joint degenerative disease that is an exceedingly common problem associated with aging. Aging is the principal risk factor for OA, but damage-related physiopathology of articular chondrocytes probably drives the mechanisms of joint degeneration by a progressive decline in the homeostatic and regenerative capacity of cells. Cellular aging is the manifestation of a complex interplay of cellular and molecular pathways underpinned by transcriptional, translational, and epigenetic mechanisms and niche factors, and unraveling this complexity will improve our understanding of underlying molecular changes that affect the ability of the articular cartilage to maintain or regenerate itself. This insight is imperative for developing new cell and drug therapies for OA disease that will target the specific causes of age-related functional decline. This review explores the key age-related changes within articular chondrocytes and discusses the molecular mechanisms that are commonly perturbed as cartilage ages and degenerates. Current efforts and emerging potential therapies in treating OA that are being employed to halt or decelerate the aging processes are also discussed.

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Age-associated (cardio)metabolic diseases and cross-talk between adipose tissue and skeleton: endocrine aspects

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2014-0030 ◽

2014 ◽

Vol 20 (1) ◽

Cited By ~ 4

Author(s):

Silvia Migliaccio ◽

Emanuela A. Greco ◽

Antonio Aversa ◽

Andrea Lenzi

Keyword(s):

Cardiovascular Diseases ◽

Muscle Mass ◽

Fat Mass ◽

Successful Aging ◽

Molecular Mechanisms ◽

Metabolic Diseases ◽

The Elderly ◽

Mortality And Morbidity ◽

Age Related ◽

Age Related Changes

AbstractAged individuals continue to increase in number, and it is important to understand the pathophysiological mechanisms of age-related changes in order to develop interventions that could contribute to “successful aging”. Metabolic and hormonal factors, age-related changes in body composition, and a decline in physical activity are all involved in the tendency to lose muscle mass, to gain fat mass, and, also, to experience bone loss. Obesity, sarcopenia, and osteoporosis are important widespread health problems that lead to high prevalence of both mortality and morbidity. Indeed, during the last decades, obesity and osteoporosis have become a major health threat around the world. Aging increases the risk of developing obesity, sarcopenia, osteoporosis, and, also, cardiovascular diseases. A reduction of both bone and muscle mass with a corresponding increase of fat mass and inflammation and hormonal imbalance in the elderly lead to and may synergistically increase cardiovascular diseases. This review will focus on the relationship among these different medical situations, trying to clarify the cellular and molecular mechanisms.

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