Cellular senescence in aging and age-related disease: from mechanisms to therapy

Nature Medicine, Journal Year: 2015, Volume and Issue: 21(12), P. 1424 - 1435

Published: Dec. 1, 2015

Language: Английский

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Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines

Frontiers in Immunology, Journal Year: 2018, Volume and Issue: 9

Published: April 9, 2018

Cytokine dysregulation is believed to play a key role in the remodeling of immune system at older age, with evidence pointing an inability fine-control systemic inflammation, which seems be marker unsuccessful aging. This reshaping cytokine expression pattern, progressive tendency toward pro-inflammatory phenotype has been called 'inflamm-aging'. Despite research there no clear understanding about causes 'inflamm-aging' that underpin most major age-related diseases including atherosclerosis, diabetes, Alzheimer's disease, rheumatoid arthritis, cancer and aging itself. While inflammation part normal repair response for healing, essential keeping us safe from bacterial viral infections noxious environmental agents, not all good. When becomes prolonged persists, it can become damaging destructive. Several common molecular pathways have identified are associated both low-grade inflammation. The change redox balance, increase senescent cells SASP decline effective autophagy trigger inflammasome, suggest may possible delay itself by suppressing mechanisms or improving timely resolution Conversely learning genetic long-lived cohorts who exemplify good quality Here we will discuss some current ideas highlight appear contribute imbalance dysregulation, 'inflammageing' parainflammation. Evidence these findings drawn cardiovascular disease two

Language: Английский

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The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4

Science, Journal Year: 2015, Volume and Issue: 349(6255)

Published: Sept. 24, 2015

Cellular senescence is a terminal stress-activated program controlled by the p53 and p16(INK4a) tumor suppressor proteins. A striking feature of senescence-associated secretory phenotype (SASP), pro-inflammatory response linked to promotion aging. We have identified transcription factor GATA4 as SASP regulator. stabilized in cells undergoing required for SASP. Normally, degraded p62-mediated selective autophagy, but this regulation suppressed during senescence, thereby stabilizing GATA4. turn activates NF-κB initiate facilitate senescence. activation depends on DNA damage regulators ATM ATR, not or p16(INK4a). accumulates multiple tissues, including aging brain, could contribute its associated inflammation.

Language: Английский

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Sarcopenic obesity or obese sarcopenia: A cross talk between age-associated adipose tissue and skeletal muscle inflammation as a main mechanism of the pathogenesis

Ageing Research Reviews, Journal Year: 2016, Volume and Issue: 35, P. 200 - 221

Published: Oct. 7, 2016

Language: Английский

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Mechanisms of Dysfunction in the Aging Vasculature and Role in Age-Related Disease

Circulation Research, Journal Year: 2018, Volume and Issue: 123(7), P. 825 - 848

Published: Sept. 13, 2018

Advancing age promotes cardiovascular disease (CVD), the leading cause of death in United States and many developed nations. Two major age-related arterial phenotypes, large elastic artery stiffening endothelial dysfunction, are independent predictors future CVD diagnosis likely responsible for development older adults. Not limited to traditional CVD, these changes vasculature also contribute other diseases that influence mammalian health span potential life span. This review explores mechanisms dysfunction at tissue level via inflammation oxidative stress cellular Klotho energy-sensing pathways (AMPK [AMP-activated protein kinase], SIRT [sirtuins], mTOR [mammalian target rapamycin]). We discuss how long-term calorie restriction—a span- span-extending intervention—can prevent vascular phenotypes through prevention deleterious alterations mechanisms. Lastly, we emerging novel aging, including senescence genomic instability within cells vasculature. As population adults steadily expands, elucidating molecular with is critical better direct appropriate measured strategies use pharmacological lifestyle interventions reduce risk this population.

Language: Английский

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Mitochondrial dysfunction and oxidative stress in aging and cancer

Oncotarget, Journal Year: 2016, Volume and Issue: 7(29), P. 44879 - 44905

Published: June 5, 2016

Aging and cancer are the most important issues to research. The population in world is growing older, incidence of increases with age. There no doubt about linkage between aging cancer. However, molecular mechanisms underlying this association still unknown. Several lines evidence suggest that oxidative stress as a cause and/or consequence mitochondrial dysfunction one main drivers these processes. Increasing ROS levels products stress, which occur age-related disorders, were also found This review focuses on similarities ageing-associated cancer-associated their common phenotype.

Language: Английский

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Identification of Senescent Cells in the Bone Microenvironment

Journal of Bone and Mineral Research, Journal Year: 2016, Volume and Issue: 31(11), P. 1920 - 1929

Published: June 24, 2016

ABSTRACT Cellular senescence is a fundamental mechanism by which cells remain metabolically active yet cease dividing and undergo distinct phenotypic alterations, including upregulation of p16Ink4a, profound secretome changes, telomere shortening, decondensation pericentromeric satellite DNA. Because senescent accumulate in multiple tissues with aging, these the dysfunctional factors they secrete, termed senescence-associated secretory phenotype (SASP), are increasingly recognized as promising therapeutic targets to prevent age-related degenerative pathologies, osteoporosis. However, cell type(s) within bone microenvironment that undergoes aging vivo has remained poorly understood, largely because previous studies have focused on cultured cells. Thus young (age 6 months) old 24 mice, we measured SASP markers highly enriched populations, all rapidly isolated from bone/marrow without vitro culture. In both females males, p16Ink4a expression real-time quantitative polymerase chain reaction (rt-qPCR) was significantly higher B cells, T myeloid osteoblast progenitors, osteoblasts, osteocytes. Further, quantification distension satellites (SADS), ie, large-scale unraveling DNA, revealed more osteocytes compared cortices (11% versus 2%, p < 0.001). addition, primary mice had sixfold (p 0.001) dysfunction-induced foci (TIFs) than mice. Corresponding age-associated accumulation several also showed dramatic These data show subset various lineages become senescent, although predominantly develop SASP. Given critical roles orchestrating remodeling, our findings suggest their may contribute loss. © 2016 American Society for Bone Mineral Research

Language: Английский

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Cellular and molecular biology of aging endothelial cells

Journal of Molecular and Cellular Cardiology, Journal Year: 2015, Volume and Issue: 89, P. 122 - 135

Published: Feb. 2, 2015

Language: Английский

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Redefining Chronic Inflammation in Aging and Age-Related Diseases: Proposal of the Senoinflammation Concept

Aging and Disease, Journal Year: 2018, Volume and Issue: 10(2), P. 367 - 367

Published: Dec. 13, 2018

Age-associated chronic inflammation is characterized by unresolved and uncontrolled with multivariable low-grade, systemic responses that exacerbate the aging process age-related diseases. Currently, there are two major hypotheses related to involvement of in process: molecular inflammaging. However, neither these satisfactorily addresses inflammation, considering recent advances have been made research. A more comprehensive view has a scope beyond conventional view, therefore required. In this review, we discuss newly emerging data on multi-phase inflammatory networks proinflammatory pathways as they relate aging. We describe upregulation nuclear factor (NF)-κB signaling, cytokines/chemokines, endoplasmic reticulum (ER) stress, inflammasome, lipid accumulation. The later sections review present our expanded senescent term "senoinflammation", propose here novel concept. As described discussion, senoinflammation provides schema highlighting important ever-increasing roles senescence-associated secretome, ER TLRs, microRNAs, which support It hoped new concept opens wider deeper avenues for basic research insights into anti-inflammatory therapeutic strategies targeting multiple mediators underlie pathophysiological process.

Language: Английский

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Inflammaging and Oxidative Stress in Human Diseases: From Molecular Mechanisms to Novel Treatments

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(18), P. 4472 - 4472

Published: Sept. 10, 2019

It has been proposed that a chronic state of inflammation correlated with aging known as inflammaging, is implicated in multiple disease states commonly observed the elderly population. Inflammaging associated over-abundance reactive oxygen species cell, which can lead to oxidation and damage cellular components, increased inflammation, activation cell death pathways. This review focuses on inflammaging its contribution various age-related diseases such cardiovascular disease, cancer, neurodegenerative diseases, obstructive pulmonary diabetes, rheumatoid arthritis. Recently published mechanistic details roles will also be discussed. Advancements potential treatments ameliorate oxidative stress, consequently, reduce morbidity explored.

Language: Английский

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