Could stress granules be involved in age-related diseases?

as a safeguard program that limits the proliferative capacity of cells when exposed to endogenous or exogenous stress signals [1, 2]. However, the senescence phenotype is also considered as a sign that the life span of a cell has reached its end. Indeed, in the early 1960s, Hayflick and Moorhead showed that despite the maintenance of optimal culturing conditions for a long period of time, normal cells do not proliferate forever [3-5]. For example, they observed that normal human diploid fibroblasts have a limited proliferation capacity and after a finite number of population doubling, they stop dividing and enter senescence. The occurrence of replicative senescence has been demonstrated for most cell types, with a few relevant exceptions including embryonic germ cells [6]. In human cells, the primary cause of cellular senescence appears to be the progressive shortening of telomeres, which are DNA structures at the end of eukaryotic chromosomes [7-9]. Senescence can also be induced by non-telomeric signals, termed " premature " or " accelerated " senescence [10]. Senescence-inducing signals, such as DNA-damage response (DDR) and oxidative stress (OS), usually engage either the p53 or the cyclin-dependent kinase inhibitor p16 pathway [11-14]. Active p53 establishes senescence, in part, by inducing the expression of the cyclin-dependent kinase inhibitor p21 cip , which suppresses the phosphorylation of the retinoblastoma protein pRB, leading to its inactivation [15]. The importance of the senescence phenotype is underscored by the fact that this condition could trigger two Commentary opposite outcomes. Due to its antiproliferative effect, senescence is activated to prevent further growth of transformed or sick cells that are subsequently eliminated by the immune system [10, 16]. This effect has mainly been observed in young organisms, and as such senescence is considered a natural tumor suppressor mechanism [16-19]. On the other hand, the situation seems to change in aged individuals. Indeed, several studies have suggested that as we age, many senescent cells escape the immune system and end up accumulating in different tissues for a long period of time, which correlates with age-related diseases such as cancer [1, 16, 20]. This functional dichotomy of the senescence phenotype raises questions such as how and why the same conditions could lead to opposite outcomes depending on age. While the answers to these questions are still elusive, it is possible that the switch of senescent cells from being a natural break of tumor growth to becoming promoters of malignancy …