Since its discovery more than 50 years ago and until recently, cellular senescence has been primarily associated with permanent withdrawal from the cell cycle, which was suggested to contribute to organismal ageing in a cell-autonomous manner, whereby senescent cells accumulate during ageing and prevent tissue self-renewal. Concomitantly, this stable cell cycle arrest was viewed as a barrier to aberrant cell proliferation during tumour initiation, raising the question of how the accumulation of senescent cells during ageing and the increased susceptibility to cancer with age could be reconciled.
In the past 10 years our understanding of the impact of cellular senescence on cancer development and ageing has largely evolved owing to the discovery of paracrine effects associated with senescence, known as the senescence-associated secretory phenotype (SASP). Numerous proteins covering a wide range of biological activities, such as inflammation, immunity, fibrosis, wound healing and reprogramming, have been shown to be secreted by senescent cells (Coppé et al., 2008). Recently, these senescent-associated secreted factors (SASFs) have been extended to lipids (Loo et al., 2017).
SASP secretome can be flexibly regulated
Even though the details of the SASF profiles of different cell types remain unknown, it is now apparent that SASP does not comprise a single response but rather that SASF expression and thus the SASP secretome can be flexibly regulated, resulting in different types of SASP (Herranz et al., 2015; Laberge et al., 2015; Hoare et al., 2016). Accordingly, depending on SASF composition and signal duration, local tissue environment and the type of the signal-receiving cell, senescent cells might communicate largely different, even opposing, instructions; for instance, tissue fibrosis versus wound healing or paracrine senescence and degeneration versus cell proliferation and reprogramming.
In summary, the discovery that senescent cells communicate with their environment to control different behaviours largely modifies the previous dogma of cell senescence as a dormant state and advocates for its multifunctionality, which now needs to be explored in more detail.
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The author declares no competing interests.
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Bernard, D. Instructive power of senescence. Nat Rev Mol Cell Biol 19, 618 (2018). https://doi.org/10.1038/s41580-018-0042-x