Considering Cellular Senescence in Aging

A mini-review on the topic of cellular senescence, one of the contributing causes of degenerative aging:

Replicative cellular senescence was first described in cell culture as an irreversible growth arrest triggered by the accumulation of cell divisions in human fibroblasts. It has since been demonstrated in virtually all vertebrate species and cell types that have been examined. Telomere shortening due to replicative exhaustion was the first cause of senescence to be well understood. In the last decade, however, it has become evident that cellular senescence can be triggered by many intrinsic and extrinsic stimuli, including the activation of oncogenes, ionizing and ultraviolet irradiation, reactive oxygen species, pharmacological agents that modify DNA or chromatin, and even nutrient imbalances and ill-described cell culture stresses.

Recent data have implicated cellular senescence as an important in vivo tumor suppression mechanism. However, solid connections between cellular senescence and organismal aging have been slower to emerge. An important impediment has been the lack of reliable assays to distinguish senescent cells from the majority of healthy but quiescent cells found in normal tissues. While a few years ago it was questioned whether senescent cells existed in vivo in appreciable numbers, today it is increasingly evident that they accumulate with age as well as at sites of age-associated pathologies.

Implication of cellular senescence in stem cell aging has added renewed credence for its importance in species with considerable renewable tissues. Studies in mouse models lacking p16Ink4a-positive senescent cells, as a result of p16Ink4a gene inactivation or drug-induced cell clearance, have implied a causal link between senescence and age-related functional decline of tissues and organs. This together with the discovery that some of the major aging-related diseases are characterized by accumulation of senescent cells has raised the possibility that therapeutic removal of senescent cells may improve healthy lifespan.



The editorial for the paper says that "recent data have implicated cellular senescence as an important in vivo tumor suppression mechanism." I looked at the source article, and it says that presence of senescent cells in pre-malignant tumors inhibits the growth of those tumors (though it's more complicated than that), and as far as I can tell not just because some cells are becoming post-mitotic (but maybe I'm misunderstanding). That's sort of strange, since if I remember right there was a different Mayo clinic paper saying that the cellular environment created by the accumulation of senescent cells facilitates the formation of cancers. So are they providing contrary evidence to this claim, and saying that accumulation of senescent cells in some tissue prevents the occurrence of cancer? Might this be a reason to be a bit worried about side-effects from future senescent-cell clearing therapies? Or is this only a worry if you already have a pre-malignant tumor?

Posted by: gheme at February 3rd, 2014 2:51 PM

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