Review highlights the interconnected roles of apoptosis, cellular senescence in cancer and aging -
damage A common feature of cancer and aging is the reduced capacity cells to respond to stress-induced DNA or cellular structures. Specifically, changes occur in the protective process of apoptosis and cellular senescence, whose roles in cancer and aging are carefully examined by Cerella et al. in Current Drug Targets (Bentham Science Publishers). The authors describe the evidence that these processes are governed by separate ways but intertwined. Understanding the precise mechanisms, they conclude, could lead to combination therapies for cancer and aging able to exploit the advantages of both apoptosis and senescence, while limiting the disadvantages of both.
The review highlights the relevant anti-apoptotic mechanisms for cancer therapy (eg. The inhibition of Bcl-2 family members blocking cell death, or COX-2, whose aberrant expression is correlated with the chronic inflammation and the most aggressive forms of colorectal cancer). The authors also discuss the dual nature of apoptosis in aging, contrasting its withdrawal from cell protection "damaged" by attrition of telomeres - a characteristic of aging -. With respect to the reduction of the lifetime of recently observed in Drosophila having hyperactive apoptosis
Similarly, if the cellular senescence is indicated as being an alternative to apoptosis, blocking damaged cells proliferate, it is also capable of promoting tumorigenesis and aging. The review presents the current knowledge about cellular senescence avoidance, as well as clues to its reversibility.
Cerella et al. find consensus on the complex interactions between the programs of apoptosis and senescence: we can save the other, or they can play equally essential complementary roles. Importantly, the authors note that some cancer treatments triggering apoptosis effectively activate senescence, too. Sensitivity to epigenetic mechanisms thereof may provide a means for reactivating the senescence of cancer cells, thereby improving current therapies. However, for combined treatments, researchers need to decouple the beneficial effects (anti-cancer, anti-aging) of those unwanted (tumor growth and aging).
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