Yousefzadeh Matthew J, Melos Kendra I, Angelini Luise, Burd Christin E, Robbins Paul D, Niedernhofer Laura J
Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, USA.
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
Methods Mol Biol. 2019;1896:203-230. doi: 10.1007/978-1-4939-8931-7_17.
Senescent cells accumulate in multiple tissues as virtually all vertebrate organisms age. Senescence is a highly conserved response to many forms of cellular stress intended to block the propagation of damaged cells. Senescent cells have been demonstrated to play a causal role in aging via their senescence-associated secretory phenotype and by impeding tissue regeneration. Depletion of senescent cells either through genetic or pharmacologic methods has been demonstrated to extend murine lifespan and delay the onset of age-related diseases. Measuring the burden and location of senescent cells in vivo remains challenging, as there is no marker unique to senescent cells. Here, we describe multiple methods to detect the presence and extent of cellular senescence in preclinical models, with a special emphasis on murine models of accelerated aging that exhibit a more rapid onset of cellular senescence.
随着几乎所有脊椎动物机体的衰老,衰老细胞会在多种组织中积累。衰老是对多种形式的细胞应激的一种高度保守的反应,旨在阻止受损细胞的增殖。衰老细胞已被证明通过其衰老相关分泌表型和阻碍组织再生在衰老过程中发挥因果作用。通过遗传或药理学方法清除衰老细胞已被证明可延长小鼠寿命并延缓与年龄相关疾病的发生。在体内测量衰老细胞的负担和位置仍然具有挑战性,因为没有衰老细胞特有的标记物。在这里,我们描述了多种在临床前模型中检测细胞衰老的存在和程度的方法,特别强调了表现出更快细胞衰老发作的加速衰老小鼠模型。