Fabrizio Paola, Longo Valter D
Andrus Gerontology Center, Division of Biogerontology, University of Southern California, Los Angeles, CA 90089-0191, USA.
Biochim Biophys Acta. 2008 Jul;1783(7):1280-5. doi: 10.1016/j.bbamcr.2008.03.017. Epub 2008 Apr 10.
Saccharomyces cerevisiae is the simplest among the major eukaryotic model organisms for aging and diseases. Longevity in the chronological life span paradigm is measured as the mean and maximum survival period of populations of non-dividing yeast. This paradigm has been used successfully to identify several life-regulatory genes and three evolutionary conserved pro-aging pathways. More recently, Schizosaccharomyces pombe has been shown to age chronologically in a manner that resembles that of S. cerevisiae and that depends on the activity of the homologues of two pro-aging proteins previously identified in the budding yeast. Both yeast show features of apoptotic death during chronological aging. Here, we review some fundamental aspects of the genetics of chronological aging and the overlap between yeast aging and apoptotic processes with particular emphasis on the identification of an aging/death program that favors the dedifferentiation and regrowth of a few better adapted mutants generated within populations of aging S. cerevisiae. We also describe the use of a genome-wide screening technique to gain further insights into the mechanisms of programmed death in populations of chronologically aging S. cerevisiae.
酿酒酵母是用于衰老和疾病研究的主要真核模式生物中最简单的一种。在时序寿命范式中,长寿是以非分裂酵母群体的平均和最大存活期来衡量的。该范式已成功用于鉴定多个寿命调控基因和三条进化保守的促衰老途径。最近,裂殖酵母已被证明能以类似于酿酒酵母的方式进行时序衰老,且这种衰老依赖于先前在芽殖酵母中鉴定出的两种促衰老蛋白的同源物的活性。在时序衰老过程中,两种酵母都表现出凋亡死亡的特征。在此,我们综述时序衰老遗传学的一些基本方面以及酵母衰老与凋亡过程之间的重叠,特别强调鉴定一种衰老/死亡程序,该程序有利于衰老的酿酒酵母群体中产生的一些适应性更强的突变体的去分化和再生长。我们还描述了使用全基因组筛选技术来进一步深入了解时序衰老的酿酒酵母群体中程序性死亡的机制。