It is believed that postponing ageing is more effective and less expensive than the treatment of particular age-related diseases. Compounds which could delay symptoms of ageing, especially natural products present in a daily diet, are intensively studied. One of them is curcumin. It causes the elongation of the lifespan of model organisms, alleviates ageing symptoms and postpones the progression of age-related diseases in which cellular senescence is directly involved. It has been demonstrated that the elimination of senescent cells significantly improves the quality of life of mice. There is a continuous search for compounds, named senolytic drugs, that selectively eliminate senescent cells from organisms. In this paper, we endeavor to review the current knowledge about the anti-ageing role of curcumin and discuss its senolytic potential.

Senescence of cancer cells is an important outcome of treatment of many cancer types. Cell senescence is a permanent cell cycle arrest induced by stress conditions, including DNA damage. DNA damage activates DNA damage response (DDR), which involves members of the phosphatidylinositol 3-kinase-related kinase (PIKK) superfamily: protein kinases ATM, ATR, and DNA-PKcs. The so-far collected data indicate that ATM, with its downstream targets CHK2, p53, and p21, is the key protein involved in DDR-dependent senescence. It was also documented that the so-called senescence-associated secretory phenotype-SASP relies on ATM/CHK2, and not on p53 signaling. Moreover, genotoxic agents used in cancer treatment can activate NF-κB, which also induces transcription of SASP genes. In this paper, we have studied the involvement of three PIKK family members in colon cancer cell senescence and connection between DNA-damage-induced senescence and NF-κB-regulated SASP in p53-proficient and p53-deficient colon cancer cells treated with doxorubicin. We showed that doxorubicin induced cell senescence in both p53+/+ and p53−/− HCT116 cells, proving that this process is p53-independent. Senescence was successfully abrogated by a PIKK inhibitor, caffeine, or by simultaneous silencing of three PIKKs by specific siRNAs. By silencing individual members of PIKK family and analyzing common markers of senescence, the level of p21 and SA-β-Gal activity, we came to the conclusion that ATR kinase is crucial for the onset of senescence as, in contrast to ATM and DNA-PKsc, it could not be fully substituted by other PIKKs. Moreover, we showed that in case of silencing the three PIKKs, there was no SASP reduction accompanying the decrease in the level of p21 and SA-β-Gal (Senescence-Associated-β-Galactosidase) activity; whereas knocking down the NF-κB component, p65, abrogated SASP, but did not affect other markers of senescence, proving that DNA damage regulated senescence independently and NF-κB evoked SASP.