Abstract
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.
Highlights
The field of cellular senescence has witnessed a marked explosion in the last decades as a multitude of novel roles in both physiology and disease have been attributed to this intriguing phenomenon
Senescent cells are generally low in number within an organism, even in aged animals [67,90]. These factors, together with the heterogeneity of the senescent programme and the intrinsic complexity of a living organism, hinder the assessment of cellular senescence in vivo. It is for this reason that substantial efforts are currently being made in order to provide more robust and reliable strategies for the detection and assessment of senescence in fixed tissues and living animals
We present a detailed description of the biomarkers and techniques most commonly used for the assessment of cellular senescence in vitro and in vivo
Summary
The field of cellular senescence has witnessed a marked explosion in the last decades as a multitude of novel roles in both physiology and disease have been attributed to this intriguing phenomenon. This is highlighted in a recent meta-review, where the authors found a positive correlation between senescence and ageing in different tissues, but the findings varied substantially depending on the identification technique employed [27] These barriers have hampered our ability to detect senescent cells confidently and, as a consequence, a complete picture of the role that cellular senescence plays within tissues and living organism remains uncovered. We suggest the verification of at least three different traits, including (a) the halt of the cell cycle progression, (b) a relevant structural change (such as the increased lysosomal mass, multinucleation, senescence-associated heterochromatic foci (SAHFs), increased number of vacuoles, the loss of lamin B1 and a flattened and enlarged shape) and (c) an additional trait that is known to be specific for that subtype of senescence being tested (for instance, DNA damage-related markers, increased ROS levels, upregulation of specific SASP factors, etc.) (Fig. 2A). Increased lysosomal content and senescence-associated b-galactosidase (SA-b-Gal)
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