Department of Biological Sciences, Brock University, St. Catharines, ON, Canada L2S 3A1.
Mech Ageing Dev. 2011 Jun-Jul;132(6-7):287-97. doi: 10.1016/j.mad.2011.06.002. Epub 2011 Jun 15.
Cellular stress resistance is generally associated with longevity, but the mechanisms underlying this phenotype are not clear. In invertebrate models there is a clear role for heat shock proteins (Hsps) and organelle-specific unfolded protein responses (UPR) in longevity. However, this has not been demonstrated in vertebrates. Some Hsp amino acid sequences are highly conserved amongst mammals and birds. We used antibodies recognizing conserved regions of Hsp60 (primarily mitochondrial), Hsp70 (primarily cytosolic), GRP78 (Bip) and GRP94 (endoplasmic reticulum) to measure constitutive levels of these proteins in brain, heart and liver of 13 mammalian and avian species ranging in maximum lifespan from 3 to 30 years. In all three tissues, the expression of these proteins was highly correlated with MLSP, indicating higher basal levels of Hsp expression are characteristic of longer-lived species. We also quantified the levels of Hsp60, Hsp70 and GRP78 in brain and heart tissue of young adult (6-7 month old) Snell dwarf mice and normal littermates. Snell dwarf mice are characterized by a single gene mutation that is associated with an ∼50% increase in lifespan. However, neither Hsp60, nor Hsp70, nor GRP78 levels were elevated in brain or heart tissue from Snell dwarf mice compared to normal littermates.
细胞应激抗性通常与长寿有关，但这种表型的机制尚不清楚。在无脊椎动物模型中，热休克蛋白（Hsps）和细胞器特异性未折叠蛋白反应（UPR）在长寿中起着明确的作用。然而，这在脊椎动物中尚未得到证明。一些 Hsp 氨基酸序列在哺乳动物和鸟类中高度保守。我们使用识别 Hsp60（主要是线粒体）、Hsp70（主要是细胞质）、GRP78（Bip）和 GRP94（内质网）保守区域的抗体，测量了 13 种哺乳动物和鸟类物种大脑、心脏和肝脏中这些蛋白质的组成型水平，这些物种的最大寿命范围从 3 年到 30 年不等。在所有三种组织中，这些蛋白质的表达与 MLSP 高度相关，这表明更高的基础 Hsp 表达水平是长寿物种的特征。我们还定量测定了年轻成年（6-7 个月大）Snell 矮小鼠和正常同窝仔鼠大脑和心脏组织中 Hsp60、Hsp70 和 GRP78 的水平。Snell 矮小鼠的特征是单个基因突变，与寿命延长约 50%有关。然而，与正常同窝仔鼠相比，Snell 矮小鼠大脑或心脏组织中的 Hsp60、Hsp70 或 GRP78 水平均未升高。
