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Received Feb 15, 2018; Accepted Feb 15, 2018
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The term cellular senescence was used in 1961 for the first time by Hayflick and Moorhead [1], to define the mechanism determining the irreversible loss of the proliferative activity of human somatic cells [1]. In this respect, cellular senescence has been usually viewed as one of the regulatory mechanisms able to stop the eventual uncontrolled proliferation of old and injured cells, mediating an activity likely similar to a tumour suppressor gatekeeper [2]. Accordingly, oncogene overexpression (i.e., H-ras) in primary cells is sufficient to trigger cellular senescence, a phenomenon defined oncogene-induced senescence [2]. Indeed, negation or bypass of oncogene-induced senescence is considered an obligatory step to develop a tumour. Later, other groups discovered that cellular senescence also occurs in differentiated cells exposed to several stressors, mainly DNA-damaging agents such as prooxidant molecules, radiation, and chemotherapeutics [3–5]. Increasing evidence has highlighted various physiological roles of cellular senescence, consequently providing a putative evolutionary explanation for this biological phenomenon. For instance, in 2013, Muñoz-Espín et al. and Storer et al. groups underlined a crucial role for cellular senescence in mammalian embryonic development by studying mouse, chick, and human embryos [6, 7]. In this context, senescence promotes tissue remodeling and it seems to represent the “father evolutional mechanism” of damage-induced senescence. In 2014, Demaria et al.’s group [8] showed that senescent fibroblasts and endothelial cells appear very early in response to a cutaneous wound, where they accelerate wound closure by inducing myofibroblast differentiation through the secretion of platelet-derived growth factor AA (PDGF-AA). In addition, it has been also demonstrated that forced cellular reprogramming induces senescence, and senescent cells (SCs) create a permissive environment for reprogramming itself [9]. This evidence leads to an interesting hypothesis based on the concept that SCs act as a trigger of tissue remodeling, following a precise regulated succession of events, characterized by the arrest of their proliferative activity and release of mediators to recruit innate immune cells, consequently promoting tissue regeneration and their elimination. These steps may result uncompleted in old tissues or...