Sir2 deletion prevents lifespan extension in 32 long-lived mutants.
Sir2 deletion prevents lifespan extension in 32 long-lived mutants.
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DOI：
10.1111/j.1474-9726.2011.00742.x
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发表时间：
2011-12
期刊：
影响因子：
7.8
通讯作者：
Kaeberlein M
中科院分区：
文献类型：
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作者：
Delaney JR;Sutphin GL;Dulken B;Sim S;Kim JR;Robison B;Schleit J;Murakami CJ;Carr D;An EH;Choi E;Chou A;Fletcher M;Jelic M;Liu B;Lockshon D;Moller RM;Pak DN;Peng Q;Peng ZJ;Pham KM;Sage M;Solanky A;Steffen KK;Tsuchiya M;Tsuchiyama S;Johnson S;Raabe C;Suh Y;Zhou Z;Liu X;Kennedy BK;Kaeberlein M
建议激活 Sir2-直系同源物以延长饮食限制 (DR) 下游的寿命。在这里，我们描述了 32 种不同的寿命延长突变和四种饮食限制方法对短命 Sir2Δ 酵母菌株复制寿命 (RLS) 的影响的检查。在每种情况下，删除 SIR2 都会阻止 RLS 延伸；然而，在某些情况下，当 SIR2 和 FOB1 都被删除时，RLS 扩展会恢复，这表明 RLS 扩展并不直接需要 SIR2。这些发现表明，抑制 Sir2Δ 寿命缺陷是长寿干预措施中罕见的表型，并表明 Sir2Δ 细胞通过与野生型细胞不同的机制快速衰老。他们还证明，在短暂的背景下（例如缺乏去乙酰化酶的细胞或动物）未能观察到寿命延长，应谨慎解释。
Activation of Sir2-orthologs is proposed to increase lifespan downstream of dietary restriction (DR). Here we describe an examination of the effect of 32 different lifespan-extending mutations and four methods of dietary restriction on replicative lifespan (RLS) in the short-lived sir2Δ yeast strain. In every case, deletion of SIR2 prevented RLS extension; however, RLS extension was restored when both SIR2 and FOB1 were deleted in several cases, demonstrating that SIR2 is not directly required for RLS extension. These findings indicate that suppression of the sir2Δ lifespan defect is a rare phenotype among longevity interventions and suggest that sir2Δ cells senesce rapidly by a mechanism distinct from that of wild-type cells. They also demonstrate that failure to observe life span extension in a short-lived background, such as cells or animals lacking sirtuins, should be interpreted with caution.