Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
Autophagy. 2012 Aug;8(8):1273-4. doi: 10.4161/auto.20917. Epub 2012 Jun 1.
Fibroblasts from long-lived pituitary dwarf mutants, including Snell dwarf, Ames dwarf and the growth hormone receptor knockout (GHRKO) mice, are resistant in culture to multiple forms of lethal stress. We found that fibroblasts from Snell dwarf and GHRKO mice are more susceptible than control cells to autophagy induced by amino acid withdrawal or by oxidative stress. We also found evidence for lower MTOR function in dwarf cells under conditions that induce autophagy, consistent with the evidence that increased autophagy requires lower TOR activity. Our results provide new hints about the connections between autophagy and aging in long-lived mutants with alterations in GH-IGF1 levels, and suggest a role for hyperactive autophagy in the resistance of cells from these mice to lethal stresses.
长寿型垂体侏儒突变体（包括 Snell 侏儒、Ames 侏儒和生长激素受体敲除（GHRKO）小鼠）的成纤维细胞在培养中对多种形式的致死性应激具有抗性。我们发现，Snell 侏儒和 GHRKO 小鼠的成纤维细胞比对照细胞更容易受到氨基酸缺失或氧化应激诱导的自噬。我们还发现，在诱导自噬的条件下，矮鼠细胞中的 MTOR 功能较低，这与增加自噬需要较低的 TOR 活性的证据一致。我们的结果为 GH-IGF1 水平改变的长寿突变体中自噬与衰老之间的联系提供了新的线索，并表明过度活跃的自噬在这些小鼠细胞对致死性应激的抗性中起作用。
