Robust, universal biomarker assay to detect senescent cells in biological specimens

Evangelou, Konstantinos; Lougiakis, Nikolaos; Rizou, Sophia V.; Kotsinas, Athanassios; Kletsas, Dimitris; Muñoz‐Espín, Daniel; Kastrinakis, Nikolaos G.; Pouli, Nicole; Marakos, Panagiotis; Townsend, Paul A.; Serrano, Manuel; Bártek, Jiří; Gorgoulis, Vassilis G.

doi:10.1111/acel.12545

Cited by 188 publications

(151 citation statements)

References 20 publications

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“…Shortly thereafter, p19 ARF -mediated stabilization of the transcription factor p53 was identified as a feature of SNCs, providing another valuable in vivo marker of SNCs 9,33,34 . These SNC detection tools as well as additional markers, such as intracellular lipofuscin accumulation 35 , were instrumental in establishing that senescence is a consequential in vivo programme and not merely a cell culture phenomenon. For example, SA-β-Gal activity and CDKi levels were found to be elevated in both human atherosclerotic plaques 36 and in numerous aged rodent and aged primate tissues 37 (FIG.…”

Section: Discovery and Detection Of Sncsmentioning

confidence: 99%

“…The most reliable approach currently available involves the use of a combination of semi-selective markers, including SA-β-Gal, lipofuscin, loss of nuclear (HMGB1) or lamin B1, increased levels of cell cycle inhibitors — such as p16 INK4A , p14 ARF or 19 ARF as well as p21 — or commonly observed SASP factors 35,41,42,91,92 . Causality (that is, that SNCs are necessary for a particular disease) can be demonstrated by blocking the establishment of cellular senescence (through inactivation of key components of the senescence programme, such as p16 INK4A ) or more conclusively by selectively eliminating SNCs from diseased tissues and observing the impact on a disease process 7,11 .…”

Section: Senescence and Age-related Diseasesmentioning

confidence: 99%

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Senescent cells: an emerging target for diseases of ageing

Childs

Gluscevic

Baker

et al. 2017

Nat Rev Drug Discov

827

723

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Chronological age represents the single greatest risk factor for human disease. One plausible explanation for this correlation is that mechanisms that drive ageing might also promote age-related diseases. Cellular senescence, which is a permanent state of cell cycle arrest induced by cellular stress, has recently emerged as a fundamental ageing mechanism that also contributes to diseases of late life, including cancer, atherosclerosis and osteoarthritis. Therapeutic strategies that safely interfere with the detrimental effects of cellular senescence, such as the selective elimination of senescent cells (SNCs) or the disruption of the SNC secretome, are gaining significant attention, with several programmes now nearing human clinical studies.

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Section: Discovery and Detection Of Sncsmentioning

confidence: 99%

Section: Senescence and Age-related Diseasesmentioning

confidence: 99%

Senescent cells: an emerging target for diseases of ageing

Childs

Gluscevic

Baker

et al. 2017

Nat Rev Drug Discov

827

723

View full text Add to dashboard Cite

show abstract

“…New methods are being developed, some of which are focused on detecting the DNA damage response (a typical marker of critical telomere shortening) may yield better results (Choi, Kim, Kim, Kemp, & Sancar, 2015;Hewitt et al, 2012;Rossiello et al, 2017). Senescence has been studied successfully in T lymphocytes, skin, and intramuscular fat, and high-throughput methods will be available soon (Evangelou et al, 2016;Lozano-Torres et al, 2017). In addition, specific patterns of circulating proteins may exist that indirectly estimate the burden of senescence (Angelini et al, 2017;Hoffman, Lyu, Pletcher, & Promislow, 2017;Kadota et al, 2018;Menni et al, 2014;Tanaka et al, 2018;Yousefzadeh et al, 2017).…”

Section: Connec Ting the B I Ology Of Ag Ing With Ag E-a Sso Ciatedmentioning

confidence: 99%

Measuring biological aging in humans: A quest

et al. 2019

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The global population of individuals over the age of 65 is growing at an unprecedented rate and is expected to reach 1.6 billion by 2050. Most older individuals are affected by multiple chronic diseases, leading to complex drug treatments and increased risk of physical and cognitive disability. Improving or preserving the health and quality of life of these individuals is challenging due to a lack of well‐established clinical guidelines. Physicians are often forced to engage in cycles of “trial and error” that are centered on palliative treatment of symptoms rather than the root cause, often resulting in dubious outcomes. Recently, geroscience challenged this view, proposing that the underlying biological mechanisms of aging are central to the global increase in susceptibility to disease and disability that occurs with aging. In fact, strong correlations have recently been revealed between health dimensions and phenotypes that are typical of aging, especially with autophagy, mitochondrial function, cellular senescence, and DNA methylation. Current research focuses on measuring the pace of aging to identify individuals who are “aging faster” to test and develop interventions that could prevent or delay the progression of multimorbidity and disability with aging. Understanding how the underlying biological mechanisms of aging connect to and impact longitudinal changes in health trajectories offers a unique opportunity to identify resilience mechanisms, their dynamic changes, and their impact on stress responses. Harnessing how to evoke and control resilience mechanisms in individuals with successful aging could lead to writing a new chapter in human medicine.

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“…Very recently, a revolutionary hybrid histo/immuno-chemical method of a biotin-linked Sudan Black-B analog has been established to assess the senescent status in in vitro and in vivo biological settings (Evangelou et al, 2016). This method may constitute an invaluable research tool for the study of the interplay between the molecular pathways implicated in autophagy and DNA damage-induced senescence.…”

Section: Functional Outcomes Of the Ddr – Autophagy Axismentioning

confidence: 99%

DNA Damage Response and Autophagy: A Meaningful Partnership

2016

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Autophagy and the DNA damage response (DDR) are biological processes essential for cellular and organismal homeostasis. Herein, we summarize and discuss emerging evidence linking DDR to autophagy. We highlight published data suggesting that autophagy is activated by DNA damage and is required for several functional outcomes of DDR signaling, including repair of DNA lesions, senescence, cell death, and cytokine secretion. Uncovering the mechanisms by which autophagy and DDR are intertwined provides novel insight into the pathobiology of conditions associated with accumulation of DNA damage, including cancer and aging, and novel concepts for the development of improved therapeutic strategies against these pathologies.

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Robust, universal biomarker assay to detect senescent cells in biological specimens

Cited by 188 publications

References 20 publications

Senescent cells: an emerging target for diseases of ageing

Senescent cells: an emerging target for diseases of ageing

Measuring biological aging in humans: A quest

DNA Damage Response and Autophagy: A Meaningful Partnership

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