Cellular senescence refers to the stable state of cell cycle arrest in which cells lose the ability of division and proliferation.Various intracellular and extracellular stimuli can induce cell senescence.Senescent cells exhibit multiple hallmarks,such as the upregulation of cell cycle inhibitor proteins p16INK4a and p21Cipl,DNA damage responses,and structural and metabolic alterations.Another major hallmark of senescent cells is that they express and secret a variety of factors,including cytokines,chemokines,growth factors,proteases,and other bioactive molecules,defined as the senescence-associated secretory phenotype(SASP).SASP factors exert multiple biological functions through the cell autonomous autocrine manner or cell non-autonomous paracrine fashion.In this review,we summarize the composition of SASP,and point out its high heterogeneity and dynamics.We then summarize the regulatory mechanisms of SASP at various levels including transcription,post-transcription,translation,post-translational modifications,and epigenetics.Afterwards,we summarize the various biological functions of SASP,including its beneficial effects in tumor suppression,tissue repair,and embryonic development,as well as its detrimental effects in inducing cell senescence,promoting tumor occurrence and development,age-related diseases,and organismal aging.We further discuss the potential applications of the SASP,which overview the senolytic therapy for selectively clearing senescent cells and senomorphic therapy for inhibiting SASP to intervene age and age-related diseases.Finally,we outline several challenges in identifying and detecting senescent cells and SASP factors in vivo,and provide some practical recommendations and new techniques to address these challenges.
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维普
