Translation of Cellular Senescence to Novel Therapeutics: Insights From Alternative Tools and Models

Abstract

Increasing chronological age is the greatest risk factor for human diseases. Cellular senescence (CS), which is characterized by permanent cell-cycle arrest, has recently emerged as a fundamental mechanism in developing aging-related pathologies. During the aging process, senescent cell accumulation results in senescence-associated secretory phenotype (SASP) which plays an essential role in tissue dysfunction. Although discovered very recently, senotherapeutic drugs have been already involved in clinical studies. This review gives a summary of the molecular mechanisms of CS and its role particularly in the development of cardiovascular diseases (CVD) as the leading cause of death. In addition, it addresses alternative research tools including the nonhuman and human models as well as computational techniques for the discovery of novel therapies. Finally, senotherapeutic approaches that are mainly classified as senolytics and senomorphics are discussed.

Anti‐Migratory and Cytotoxic Activities of [Ga(8‐hydroxyquinolinato)3]: Roles of Endogenous Cu(II) and Drug‐Induced Phenotypic Changes

“…The transformed cells were metabolically active, as shown by reductase activity (WST‐8) assay, [20] but they did not re‐attach after trypsinization, consistent with cells undergoing terminal differentiation [21a,b] . A related process, cell senescence, [21c] was previously reported for other human cancer cell lines (MCF‐7, H1299 and PC3) treated with [GaQ 3 ], but it was not accompanied with obvious morphological changes [21] . MDA‐MB‐231 cells were isolated from a metastatic breast cancer site [17] and are predominantly of mesenchymal (invasive) phenotype, which causes their high migration rates in wound healing assays [18] in the absence of added growth factors [23] .…”