The Biological Process of Aging and the Impact of Ionizing Radiation

Al‐Jumayli, Mohammed; Brown, Stephen L.; Chetty, Indrin J.; Extermann, Martine; Movsas, Benjamin

doi:10.1016/j.semradonc.2021.11.011

Cited by 9 publications

(6 citation statements)

References 75 publications

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“…It has been widely suggested that radiation therapy may accelerate cellular senescence, leading to premature aging and age-associated diseases. Intracellular changes caused by anticancer treatments, such as radiotherapy, can lead to premature aging by altering DNA structure, gene expression, mutations mediated by transcription regulator cascades, protein expression, and increasing damage from ROS [ 2 , 173 , 174 ]. Thus, individuals undergoing radiation therapy develop age-related diseases and phenotypes earlier than members of the general population, which is probably due to tissue damage that initiates disruption of DNA structural integrity, thereby activating the DDR system [ 4 ] and accelerating aging processes [ 175 ].…”

Section: Radiation-induced Cellular Senescencementioning

confidence: 99%

“…Regardless of the inducing stimulus, senescent cells share common mechanisms for activation and maintenance of senescence, which are associated with p53, p21, p16, and pRB proteins [ 2 ]. Li et al [ 184 ] observed increased expression of p-p38, p38, and p16 INK4a proteins in the spleen of irradiated mice.…”

Section: Radiation-induced Cellular Senescencementioning

confidence: 99%

“…Every day, cell integrity is threatened not only by endogenous agents, but also by exogenous factors, among which radiation exposure occupies a key position. Recently, radiation has become widely associated with a spectrum of age-related diseases, noting that ionizing radiation (IR) itself may be a cause of premature aging [ 2 ]. Exposure to IR causes several physiological changes that can lead to DNA double-strand breaks (DSBs), thereby initiating genomic instability and metabolic system dysfunction [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

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The Molecular Mechanisms in Senescent Cells Induced by Natural Aging and Ionizing Radiation

Ibragimova,

Kussainova,

Aripova

et al. 2024

Cells

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This review discusses the relationship between cellular senescence and radiation exposure. Given the wide range of ionizing radiation sources encountered by people in professional and medical spheres, as well as the influence of natural background radiation, the question of the effect of radiation on biological processes, particularly on aging processes, remains highly relevant. The parallel relationship between natural and radiation-induced cellular senescence reveals the common aspects underlying these processes. Based on recent scientific data, the key points of the effects of ionizing radiation on cellular processes associated with aging, such as genome instability, mitochondrial dysfunction, altered expression of miRNAs, epigenetic profile, and manifestation of the senescence-associated secretory phenotype (SASP), are discussed. Unraveling the molecular mechanisms of cellular senescence can make a valuable contribution to the understanding of the molecular genetic basis of age-associated diseases in the context of environmental exposure.

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Section: Radiation-induced Cellular Senescencementioning

confidence: 99%

Section: Radiation-induced Cellular Senescencementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Molecular Mechanisms in Senescent Cells Induced by Natural Aging and Ionizing Radiation

Ibragimova,

Kussainova,

Aripova

et al. 2024

Cells

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“…Additionally, CD4 + CTLs have been detected in the circulation of supercentenarians with clonal expansion, and a study has found that CD4 + CTLs can kill senescent cells, implying their protective effects on aging‐associated diseases. 28 , 29 Since there are close relationships between radiation and aging, and radiation is utilized to induce a model of accelerated aging, 30 it is plausible that CD4 + CTLs may be generated in RIBI, and relevant investigation is of clinical significance.…”

Section: Introductionmentioning

confidence: 99%

Terminally differentiated cytotoxic CD4⁺ T cells were clonally expanded in the brain lesion of radiation‐induced brain injury

Ma,

Zuo,

et al. 2024

CNS Neurosci Ther

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BackgroundAccumulating evidence supports the involvement of adaptive immunity in the development of radiation‐induced brain injury (RIBI). Our previous work has emphasized the cytotoxic function of CD8+ T cells in RIBI. In this study, we aimed to investigate the presence and potential roles of cytotoxic CD4+ T cells (CD4+ CTLs) in RIBI to gain a more comprehensive understanding of adaptive immunity in this context.Main TextUtilizing single‐cell RNA sequencing (scRNA‐seq), we analyzed 3934 CD4+ T cells from the brain lesions of four RIBI patients and identified six subclusters within this population. A notable subset, the cytotoxic CD4+ T cells (CD4+ CTLs), was marked with high expression of cytotoxicity‐related genes (NKG7, GZMH, GNLY, FGFBP2, and GZMB) and several chemokine and chemokine receptors (CCL5, CX3CR1, and CCL4L2). Through in‐depth pseudotime analysis, which simulates the development of CD4+ T cells, we observed that the CD4+ CTLs exhibited signatures of terminal differentiation. Their functions were enriched in protein serine/threonine kinase activity, GTPase regulator activity, phosphoprotein phosphatase activity, and cysteine‐type endopeptidase activity involved in the apoptotic signaling pathway. Correspondingly, mice subjected to gamma knife irradiation on the brain showed a time‐dependent infiltration of CD4+ T cells, an increase of MHCII+ cells, and the existence of CD4+ CTLs in lesions, along with an elevation of apoptotic‐related proteins. Finally, and most crucially, single‐cell T‐cell receptor sequencing (scTCR‐seq) analysis at the patient level determined a large clonal expansion of CD4+ CTLs in lesion tissues of RIBI. Transcriptional factor‐encoding genes TBX21, RORB, and EOMES showed positive correlations with the cytotoxic functions of CD4+ T cells, suggesting their potential to distinguish RIBI‐related CD4+ CTLs from other subsets.ConclusionThe present study enriches the understanding of the transcriptional landscape of adaptive immune cells in RIBI patients. It provides the first description of a clonally expanded CD4+ CTL subset in RIBI lesions, which may illuminate new mechanisms in the development of RIBI and offer potential biomarkers or therapeutic targets for the disease.

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“…Survivors of thoracic malignancies who receive radiotherapy may present with cardiac disease with or without deterioration of myocardial contractility after decades [ 19 , 20 ]. Ionizing radiation- (IR-) induced DNA damage, senescence-associated inflammatory factors, and ROS are also hallmarks of cardiomyocyte senescence [ 21 ]. Senescence and the DNA damage-associated >BRCA1 and p53/p21 signaling axis regulated by IR can cause cardiovascular injury, which eventually leads to RIHD [ 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Acetylation of Atp5f1c Mediates Cardiomyocyte Senescence via Metabolic Dysfunction in Radiation-Induced Heart Damage

Zeng

et al. 2022

Oxidative Medicine and Cellular Longevity

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Objective Ionizing radiation (IR) causes cardiac senescence, which eventually manifests as radiation-induced heart damage (RIHD). This study is aimed at exploring the mechanisms underlying IR-induced senescence using acetylation proteomics. Methods Irradiated mouse hearts and H9C2 cells were harvested for senescence detection. Acetylation proteomics was used to investigate alterations in lysine acetylation. Atp5f1c acetylation after IR was verified using coimmunoprecipitation (Co-IP). Atp5f1c lysine 55 site acetylation (Atp5f1c K55-Ac) point mutation plasmids were used to evaluate the influence of Atp5f1c K55-Ac on energy metabolism and cellular senescence. Deacetylation inhibitors, plasmids, and siRNA transfection were used to determine the mechanism of Atp5f1c K55-Ac regulation. Results The mice showed cardiomyocyte and cardiac aging phenotypes after IR. We identified 90 lysine acetylation sites from 70 protein alterations in the heart in response to IR. Hyperacetylated proteins are primarily involved in energy metabolism. Among them, Atp5f1c was hyperacetylated, as confirmed by Co-IP. Atp5f1c K55-Ac decreased ATP enzyme activity and synthesis. Atp5f1c K55 acetylation induced cardiomyocyte senescence, and Sirt4 and Sirt5 regulated Atp5f1c K55 deacetylation. Conclusion Our findings reveal a mechanism of RIHD through which Atp5f1c K55-Ac leads to cardiac aging and Sirt4 or Sirt5 modulates Atp5f1c acetylation. Therefore, the regulation of Atp5f1c K55-Ac might be a potential target for the treatment of RIHD.

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The Biological Process of Aging and the Impact of Ionizing Radiation

Cited by 9 publications

References 75 publications

The Molecular Mechanisms in Senescent Cells Induced by Natural Aging and Ionizing Radiation

The Molecular Mechanisms in Senescent Cells Induced by Natural Aging and Ionizing Radiation

Terminally differentiated cytotoxic CD4⁺ T cells were clonally expanded in the brain lesion of radiation‐induced brain injury

Acetylation of Atp5f1c Mediates Cardiomyocyte Senescence via Metabolic Dysfunction in Radiation-Induced Heart Damage

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The Biological Process of Aging and the Impact of Ionizing Radiation

Cited by 9 publications

References 75 publications

The Molecular Mechanisms in Senescent Cells Induced by Natural Aging and Ionizing Radiation

The Molecular Mechanisms in Senescent Cells Induced by Natural Aging and Ionizing Radiation

Terminally differentiated cytotoxic CD4+ T cells were clonally expanded in the brain lesion of radiation‐induced brain injury

Acetylation of Atp5f1c Mediates Cardiomyocyte Senescence via Metabolic Dysfunction in Radiation-Induced Heart Damage

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Terminally differentiated cytotoxic CD4⁺ T cells were clonally expanded in the brain lesion of radiation‐induced brain injury