Functional heterogeneity in senescence

Kirschner, Kristina; Rattanavirotkul, Nattaphong; Quince, Megan F.; Chandra, Tamir

doi:10.1042/bst20190109

Cited by 51 publications

(60 citation statements)

References 67 publications

(97 reference statements)

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“…As our knowledge of senescence advances at a staggering speed, so does our awareness of the complexity and heterogeneity of the senescent programme itself. It is very likely that the term cellular senescence comprises different phenotypes and cellular states, owing to the evidence that the programme implemented significantly depends on the stressor or insult, the cell type and the physiological context [26]. This complexity is exacerbated by the fact that the biomarkers used to detect cellular senescence are generally nonspecific and sometimes unreliable, and a real consensus on how to best detect and describe cellular senescence still remains to be determined.…”

Section: Introductionmentioning

confidence: 99%

A guide to assessing cellular senescence in vitro and in vivo

et al. 2020

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Cellular senescence is a physiological mechanism whereby a proliferating cell undergoes a stable cell cycle arrest upon damage or stress and elicits a secretory phenotype. This highly dynamic and regulated cellular state plays beneficial roles in physiology, such as during embryonic development and wound healing, but it can also result in antagonistic effects in age-related pathologies, degenerative disorders, ageing and cancer. In an effort to better identify this complex state, and given that a universal marker has yet to be identified, a general set of hallmarks describing senescence has been established. However, as the senescent programme becomes more defined, further complexities, including phenotype heterogeneity, have emerged. This significantly complicates the recognition and evaluation of cellular senescence, especially within complex tissues and living organisms. To address these challenges, substantial efforts are currently being made towards the discovery of novel and more specific biomarkers, optimized combinatorial strategies and the development of emerging detection techniques. Here, we compile such advances and present a multifactorial guide to identify and assess cellular senescence in cell cultures, tissues and living organisms. The reliable assessment and identification of senescence is not only crucial for better understanding its underlying biology, but also imperative for the development of diagnostic and therapeutic strategies aimed at targeting senescence in the clinic.

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Section: Introductionmentioning

confidence: 99%

A guide to assessing cellular senescence in vitro and in vivo

et al. 2020

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“…Among the key questions that need to be addressed are whether all cells respond similarly to the same oncogenic activation and whether the same oncogenic insult always results in a heterogenous OIS population. We have summarised current evidence for a functional heterogeneity in the senescence response in a recent review [69]. Studies of OIS cells and their transcriptomes in vitro and in vivo have unmasked a complex regulation of their dynamic and heterogeneous nature.…”

Section: Discussionmentioning

confidence: 99%

Induction and transmission of oncogene-induced senescence

Rattanavirotkul

Kirschner

Chandra

2020

Cell. Mol. Life Sci.

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Senescence is a cellular stress response triggered by diverse stressors, including oncogene activation, where it serves as a bona-fide tumour suppressor mechanism. Senescence can be transmitted to neighbouring cells, known as paracrine secondary senescence. Secondary senescence was initially described as a paracrine mechanism, but recent evidence suggests a more complex scenario involving juxtacrine communication between cells. In addition, single-cell studies described differences between primary and secondary senescent end-points, which have thus far not been considered functionally distinct. Here we discuss emerging concepts in senescence transmission and heterogeneity in primary and secondary senescence on a cellular and organ level.

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“…Neutralization of these SASP components with antibodies can attenuate the pro-osteoclastogenic effects of senescent cells and restrict the generation of osteoclasts [ 76 ]. In addition, SASP is released by osteocytes in an autocrine and paracrine manner and induces secondary senescence in adjacent cells exposed to it, thereby exacerbating and amplifying the senescence and inflammatory states [ 89 ]. In the context of age-related changes in bone, senescent osteocytes exhibit dramatic degeneration of cellular processes and diminished osteocyte density, resulting in vacancies in the overall cellular connection network, which could further cause defective mechanotransduction, impaired nutrient acquisition and affected intercellular signal transduction, resulting in significant bone loss [ 90 , 91 ].…”

Section: Potential Effect Of Premature Osteocyte Senescence On Bone Rmentioning

confidence: 99%

“…In the context of age-related changes in bone, senescent osteocytes exhibit dramatic degeneration of cellular processes and diminished osteocyte density, resulting in vacancies in the overall cellular connection network, which could further cause defective mechanotransduction, impaired nutrient acquisition and affected intercellular signal transduction, resulting in significant bone loss [ 90 , 91 ]. In addition to expressing SASP, senescent osteocytes are also capable of inducing DNA damage and propagating senescence to bystander cells through gap junction-dependent intercellular connections; this propagated senescence is termed senescence-induced senescence, and it creates a toxic inflammatory microenvironment to accelerate and spread its effects [ 89 , 92 ] (Fig. 4 ).…”

Section: Potential Effect Of Premature Osteocyte Senescence On Bone Rmentioning

confidence: 99%

The roles of osteocytes in alveolar bone destruction in periodontitis

Huang

Xie

et al. 2020

J Transl Med

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Periodontitis, a bacterium-induced inflammatory disease that is characterized by alveolar bone loss, is highly prevalent worldwide. Elucidating the underlying mechanisms of alveolar bone loss in periodontitis is crucial for understanding its pathogenesis. Classically, bone cells, such as osteoclasts, osteoblasts and bone marrow stromal cells, are thought to dominate the development of bone destruction in periodontitis. Recently, osteocytes, the cells embedded in the mineral matrix, have gained attention. This review demonstrates the key contributing role of osteocytes in periodontitis, especially in alveolar bone loss. Osteocytes not only initiate physiological bone remodeling but also assist in inflammation-related changes in bone remodeling. The latest evidence suggests that osteocytes are involved in regulating bone anabolism and catabolism in the progression of periodontitis. The altered secretion of receptor activator of NF-κB ligand (RANKL), sclerostin and Dickkopf-related protein 1 (DKK1) by osteocytes affects the balance of bone resorption and formation and promotes bone loss. In addition, the accumulation of prematurely senescent and apoptotic osteocytes observed in alveolar bone may exacerbate local destruction. Based on their communication with the bloodstream, it is noteworthy that osteocytes may participate in the interaction between local periodontitis lesions and systemic diseases. Overall, further investigations of osteocytes may provide vital insights that improve our understanding of the pathophysiology of periodontitis.

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Functional heterogeneity in senescence

Cited by 51 publications

References 67 publications

A guide to assessing cellular senescence in vitro and in vivo

A guide to assessing cellular senescence in vitro and in vivo

Induction and transmission of oncogene-induced senescence

The roles of osteocytes in alveolar bone destruction in periodontitis

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