A Possible Biomarker for Senescent Cells

Posted: May 19, 2013 at 2:57 am

There are any number of techniques under development that allow individual cells to be destroyed provided that you can distinguish them from their neighbors: the challenge is in finding characteristic differences in the cells you want destroyed, such as cancer cells or senescent cells. Most of the efforts aimed at producing targeted cell destruction therapies are taking place in the cancer research community, but senescent cells accumulate with age and contribute to degenerative aging - they must also be destroyed. Unfortunately good ways to target senescent cells are somewhat lacking. Candidate mechanisms are emerging, however, and here is another of them:

Due to its role in aging and antitumor defense, cellular senescence has recently attracted increasing interest. However, [the] detection of senescent cells remains difficult due to the lack of specific biomarkers. ndeed, most determinants of cellular senescence, such as the upregulation of p53, p16Ink4a, p21WAF/CIP1 or SASP-associated cytokines, are not exclusively observed in senescence, but can also occur in other types of stress responses. In addition, alterations like SAHF or DNA-SCARS formation are frequently observed, but not necessarily a mandatory feature or exclusive to senescent cells.

The current gold standard for the detection of senescence is the so-called senescence-associated ?-galactosidase (SA-?-Gal) activity. Although SA-?-Gal has been first suggested as a distinct enzyme, its activity is derived from lysosomal ?-Gal encoded by the GLB1 gene. ?-Gal is an accepted marker of senescence, but its reliability and specificity have been questioned, as a positive ?-Gal reaction has also been detected in human cancer cells that were chemically induced to differentiate, or upon contact inhibition. Moreover, several cell types, such as epithelial cells and murine fibroblasts generally show a weak ?-Gal staining.

In the present study, we investigated several lysosomal hydrolases for their suitability as senescence markers and identified ?-fucosidase, a lysosomal glycosidase involved in the breakdown of glycoproteins, oligosaccharides and glycolipids, as a novel biomarker for senescence. We demonstrate that ?-fucosidase is upregulated [in] all canonical types of cellular senescence, including replicative, DNA damage- and oncogene-induced senescence. Our results suggest that detection of ?-fucosidase might be a highly valuable biomarker for senescence in general and in particular in those cases where SA-?-Gal activity fails to properly discriminate between senescent- and non-senescent cells.

Link: http://www.landesbioscience.com/journals/cc/article/24944/?show_full_text=true

Source:
http://www.fightaging.org/archives/2013/05/a-possible-biomarker-for-senescent-cells.php

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