Length doesn't matter—telomere damage triggers cellular senescence in the ageing heart

Brand, Thomas

doi:10.15252/embj.2019101571

Cited by 7 publications

(6 citation statements)

References 12 publications

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“…Different from proliferative cells, post-mitotic cardiomyocytes develop senescent-like phenotypes through a mechanism independent of cell division and telomere length. As characterized by persistent telomeric DNA damage, post-mitotic cardiomyocyte senescence can be mediated by mitochondrial dysfunction, which activates p21 CIP and p16 INK4a , resulting in a non-canonical Senescence-associated secretory phenotype (SASP) [ 70 , 71 ] . Studies revealed the critical role of cardiomyocyte mitochondria in cardiac function [ 72 ] .…”

Section: Telomere Shortening and Dysfunction In Cancer Survivorsmentioning

confidence: 99%

Cancer treatment-induced NAD+ depletion in premature senescence and late cardiovascular complications

Banerjee¹,

Olmsted-Davis²,

Deswal³

et al. 2022

J Cardiovasc Aging

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Numerous studies have revealed the critical role of premature senescence induced by various cancer treatment modalities in the pathogenesis of aging-related diseases. Senescence-associated secretory phenotype (SASP) can be induced by telomere dysfunction. Telomeric DNA damage response induced by some cancer treatments can persist for months, possibly accounting for long-term sequelae of cancer treatments. Telomeric DNA damage-induced mitochondrial dysfunction and increased reactive oxygen species production are hallmarks of premature senescence. Recently, we reported that the nucleus-mitochondria positive feedback loop formed by p90 ribosomal S6 kinase (p90RSK) and phosphorylation of S496 on ERK5 (a unique member of the mitogen-activated protein kinase family that is not only a kinase but also a transcriptional co-activator) were vital signaling events that played crucial roles in linking mitochondrial dysfunction, nuclear telomere dysfunction, persistent SASP induction, and atherosclerosis. In this review, we will discuss the role of NAD+ depletion in instigating SASP and its downstream signaling and regulatory mechanisms that lead to the premature onset of atherosclerotic cardiovascular diseases in cancer survivors.

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Section: Telomere Shortening and Dysfunction In Cancer Survivorsmentioning

confidence: 99%

Cancer treatment-induced NAD+ depletion in premature senescence and late cardiovascular complications

Banerjee¹,

Olmsted-Davis²,

Deswal³

et al. 2022

J Cardiovasc Aging

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“…One of the mechanisms of cellular aging is the shortening of telomeres (regions on the ends of chromosomes) [ 196 ]. It happens because of the fact that the region of the chromosome, where the DNA polymerase is located before replication, is not replicated by it.…”

Section: Cellular Types Of Stressmentioning

confidence: 99%

“…After a certain number of divisions, a significant shortening of telomeres occurs and the cell stops dividing. Telomere shortening can contribute not only to the aging of the cell and the whole organism, but also to various diseases [ 196 , 197 , 198 , 199 ]. In particular, Stein, J.Y., et al found that traumatic stress which occurs in soldiers after being captured contributes to the appearing of shorter telomeres [ 197 ].…”

Section: Cellular Types Of Stressmentioning

confidence: 99%

Some Molecular and Cellular Stress Mechanisms Associated with Neurodegenerative Diseases and Atherosclerosis

Sinyov

Рыжкова

Sazonova

et al. 2021

IJMS

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Chronic stress is a combination of nonspecific adaptive reactions of the body to the influence of various adverse stress factors which disrupt its homeostasis, and it is also a corresponding state of the organism’s nervous system (or the body in general). We hypothesized that chronic stress may be one of the causes occurence of several molecular and cellular types of stress. We analyzed literary sources and considered most of these types of stress in our review article. We examined genes and mutations of nuclear and mitochondrial genomes and also molecular variants which lead to various types of stress. The end result of chronic stress can be metabolic disturbance in humans and animals, leading to accumulation of reactive oxygen species (ROS), oxidative stress, energy deficiency in cells (due to a decrease in ATP synthesis) and mitochondrial dysfunction. These changes can last for the lifetime and lead to severe pathologies, including neurodegenerative diseases and atherosclerosis. The analysis of literature allowed us to conclude that under the influence of chronic stress, metabolism in the human body can be disrupted, mutations of the mitochondrial and nuclear genome and dysfunction of cells and their compartments can occur. As a result of these processes, oxidative, genotoxic, and cellular stress can occur. Therefore, chronic stress can be one of the causes forthe occurrence and development of neurodegenerative diseases and atherosclerosis. In particular, chronic stress can play a large role in the occurrence and development of oxidative, genotoxic, and cellular types of stress.

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“…To bridge this gap, we recently proposed a model ( Figure 1 ) outlining specific anato-physiological mechanisms relating psychological stress regulation to cellular senescence, and subsequently, age-related pathology ( Ask et al, 2018 ). The model is largely based on the prefrontal component of the central-autonomic network, the immuno reflex (or cholinergic anti-inflammatory pathway; Tracey, 2002 ), and the molecular cell biology related to generation of reactive oxygen species (e.g., Schreck and Baeuerle, 1994 ) and oxidative telomere damage ( Brand, 2019 ; Coluzzi et al, 2019 ; Wang et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…Both shorter telomeres and increased peripheral levels of inflammation are associated with increased risk for Alzheimer’s disease ( King et al, 2018 ; Wood, 2018 ; Hackenhaar et al, 2021 ). Whether shorter telomeres are a risk for cancer development might depend on cancer type ( Zhu et al, 2016 ), although damage-induced telomere dysfunction can occur irrespective of telomere length ( Victorelli and Passos, 2017 ; Brand, 2019 ). A series of studies associating vagal tone with cancer survival provided some of the first evidence suggesting that vagal modulation of the immune system could be a manner of life and death in clinical conditions ( Mouton et al, 2010 , 2012 ; Chiang et al, 2013 ; De Couck et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Prefrontally modulated vagal neuroimmunomodulation is associated with telomere length

Ask

Sütterlin

2022

Front. Neurosci.

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BackgroundAccumulated senescent cells are proposed to be one of the main drivers of age-related pathology such as dementia and cancer through disruption of tissue structure and function. We recently proposed the Neuro-Immuno-Senescence Integrative Model (NISIM), which relates prefrontally modulated vagal tone and subsequent balance between vagal and sympathetic input to the spleen to inflammatory responses leading to generation of reactive oxygen species and oxidative telomere damage.AimIn this study, we assess inflammation as a mediator in the relationship between prefrontally modulated vagal tone and leukocyte telomere length (LTL). We also assess the relationship between a recently proposed index of vagal neuroimmunomodulation (vagal tone/inflammation ratio; NIM index) and telomere length.MethodsThis study uses participant data from a large nationally representative longitudinal study since 1974 with a total of 45,000 Norwegian residents so far. A sub-sample of 131 participants from which ultrashort recordings (30 s) of vagal tone, c reactive protein, and LTL could be obtained were included in the study. Relationships were analyzed with Pearson’s correlations and hierarchical multiple linear regression using either vagal tone and CRP or the NIM index to predict telomere length.ResultsVagal tone was a significant positive predictor of telomere length but this was not mediated by c reactive protein, even after controlling for confounders. The NIM index was a significant positive predictor of telomere length, also when controlling for confounders. In a follow-up analysis simultaneously comparing telomere length between groups with high and low values of vagal tone, and between groups with high and low NIM index values, telomere length was only significantly different between NIM index groups.ConclusionThis is the first study suggesting that prefrontally modulated vagal neuroimmunomodulation is associated with telomere length thus supporting the NISIM. Results indicate that the NIM index is a more sensitive indicator of vagal neuroimmunomodulation than vagal tone and CRP in isolation.

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Length doesn't matter—telomere damage triggers cellular senescence in the ageing heart

Cited by 7 publications

References 12 publications

Cancer treatment-induced NAD+ depletion in premature senescence and late cardiovascular complications

Cancer treatment-induced NAD+ depletion in premature senescence and late cardiovascular complications

Some Molecular and Cellular Stress Mechanisms Associated with Neurodegenerative Diseases and Atherosclerosis

Prefrontally modulated vagal neuroimmunomodulation is associated with telomere length

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