Biomarkers to identify and isolate senescent cells

Abstract

Highlights There is no single biomarker which can robustly identify senescent cells. Widely used senescent cell biomarkers should be used in combination for accuracy. Technologies like tangential flow filtration can be used to isolate senescent cells. Other methods, like senolytic viruses, could be used to remove senescent cells. AbstractAging is the main risk factor for many degenerative diseases and declining health. Senescent To better understand cell aging and to reap the benefits of senescent cell removal, it is necessary to have a reliable biomarker to identify these cells. Following an introduction to cellular senescence, we discuss several classes of biomarkers in the context of their utility in identifying and/or removing senescent cells from tissues. Although senescence can be induced by a variety of stimuli, senescent cells share some characteristics that enable their identification both in vitro and in vivo. Nevertheless, it may prove difficult to identify a single biomarker capable of distinguishing senescence in all cell types. Therefore, this will not be a comprehensive review of all senescence biomarkers but rather an outlook on technologies and markers that are most suitable to identify and isolate senescent cells.

Differential expression of cell cycle and WNT pathway-related genes accounts for differences in the growth and differentiation potential of Wharton’s jelly and bone marrow-derived mesenchymal stem cells

“…In contrast to the aforementioned observations, the number of SA-β-gal-positive cells was significantly higher in BM-MSC cultures compared to WJ-MSCs throughout passages. Nevertheless, SA-β-gal activity, although associated, is not completely specific for senescence [33, 34]. Instead, it can give false-positive results when used as the sole method to identify senescence and should therefore be interpreted in combination with other biomarkers [33, 34].…”

The impact of autophagy on the development of senescence in primary tubular epithelial cells

“…SAb-GAL is a frequently used biomarker but it is known for its low specificity and enhanced activity during quiescence and in response to various forms of stress. 32 In our experiments we used cell-culture associated stress as the baseline pro-senescent factor. The additional senescence triggers, i.e.…”

The Effect of a p38 Mitogen-Activated Protein Kinase Inhibitor on Cellular Senescence of Cultivated Human Corneal Endothelial Cells

“…33,34 In addition, cyclin dependent kinase inhibitors (CKIs), such as p16 and p21, have been used as biomarkers, because cell cycle arrest is recognized as a hallmark of cellular senescence. 30 Indeed, overexpression of p21 promotes cellular senescence, 35 and downregulation of FIGURE 2. Phase-contrast images of long-term culture of HCECs with or without SB203580.…”

“…[27][28][29] As cellular senescence is heterogeneous and cell-type dependent, no single biomarker can identify cellular senescence. 30 We used several biomarkers in the present study to show that the cell density drop in HCECs is a phenotypic feature of cellular senescence. We demonstrated that low cell density HCECs, which were cultured without a p38 MAPK inhibitor, showed high positive SA-b-gal staining, a low nuclear-cytoplasm ratio, and high expression of p16 and p21.…”

“…31,32 However, the sole use of SA-b-gal as marker often yields false-positive results, necessitating the use of a combination of several markers. 30 We evaluated cell size, because membrane lipid composition and membrane biophysical properties are altered by cellular senescence, resulting in an alteration of cell size. 33,34 In addition, cyclin dependent kinase inhibitors (CKIs), such as p16 and p21, have been used as biomarkers, because cell cycle arrest is recognized as a hallmark of cellular senescence.…”