Lessons in Senescence

nouement: suicide or cancer.

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© 2005 Elsevier Science

Exogenous expression of the ras oncogene triggers senescence in human fibroblasts. Staining with DAPI reveals the gradual appearance of senescence-associated heterochromatin foci, transcriptionally silent regions of DNA. Four days after cells are infected with a ras-containing retrovirus, nuclei also show a marked colocalization between heterochromatin protein 1β and promyelocytic leukemia protein; ten days after infection, colocalization decreases. (From R. Zhang et al., Dev Cell, 8:19–30, 2005.)

When aging and damaged cells undergo apoptosis or malignant transformation, their lives reach a dramatic dénouement: suicide or cancer. But when they undergo senescence, their destiny seems drab in comparison. They irreversibly exit the cell cycle, linger indefinitely, and die of undetermined causes. Senescent fibroblasts, in particular, "get big and flat, and they look ugly," resembling fried eggs, notes Scott W. Lowe, a professor at Cold Spring Harbor Laboratory on Long Island.

For decades, senescent human cells were found only ...

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