A genomic analysis of chronological longevity factors in budding yeast
A genomic analysis of chronological longevity factors in budding yeast
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DOI：
10.4161/cc.10.9.15464
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发表时间：
2011-05-01
期刊：
影响因子：
4.3
通讯作者：
Kaeberlein, Matt
中科院分区：
文献类型：
--
作者：
Burtner, Christopher R.;Murakami, Christopher J.;Kaeberlein, Matt
按时间顺序的寿命（CLS）已被研究作为一个老化范式酵母。已经确定了一些保守的衰老基因，它们调节酵母的时间和复制寿命，以及秀丽隐杆线虫的寿命；然而，在其他模型系统中，遗传控制时间顺序寿命和衰老之间的关系的综合分析尚未报道。为了解决这个问题，我们对550个单基因缺失菌株进行了功能基因组分析，这些菌株约占酵母ORF缺失收集的纯合子二倍体缺失菌株的12%。这项研究确定了33个以前未知的CLS决定因素。我们发现，在蠕虫老化基因的酵母同源缺失或复制寿命长的缺失菌株中，增强的CLS没有显著富集，尽管注意到重叠的趋势。相比之下，从培养基生长至固定阶段酸化程度降低的筛选中鉴定出的基因缺失子集因CLS增加而富集。这些结果表明，在最常用的分析条件下，CLS的遗传控制与秀丽隐杆线虫的寿命决定因素并不强烈重叠，现有的遗传途径仅限于少数遗传途径。这些数据还进一步支持了培养基酸化在合成培养基中按时间顺序老化期间的存活中起重要作用的模型，并表明使用替代培养基条件的按时间顺序老化研究可能对多细胞真核生物的衰老提供更多信息。
Chronological life span (CLS) has been studied as an aging paradigm in yeast. A few conserved aging genes have been identified that modulate both chronological and replicative longevity in yeast as well as longevity in the nematode Caenorhabditis elegans; however, a comprehensive analysis of the relationship between genetic control of chronological longevity and aging in other model systems has yet to be reported. To address this question, we performed a functional genomic analysis of chronological longevity for 550 single-gene deletion strains, which accounts for approximately 12% of the viable homozygous diploid deletion strains in the yeast ORF deletion collection. This study identified 33 previously unknown determinants of CLS. We found no significant enrichment for enhanced CLS among deletions corresponding to yeast orthologs of worm aging genes or among replicatively long-lived deletion strains, although a trend toward overlap was noted. In contrast, a subset of gene deletions identified from a screen for reduced acidification of culture media during growth to stationary phase was enriched for increased CLS. These results suggest that genetic control of CLS under the most commonly utilized assay conditions does not strongly overlap with longevity determinants in C. elegans, with the existing confined to a small number of genetic pathways. These data also further support the model that acidification of the culture medium plays an important role in survival during chronological aging in synthetic medium, and suggest that chronological aging studies using alternate medium conditions may be more informative with regard to aging of multicellular eukaryotes.