Buck Institute for Age Research, 8001 Redwood Blvd., Novato, California 94945, USA.
Adv Exp Med Biol. 2010;694:30-7. doi: 10.1007/978-1-4419-7002-2_3.
Growth and somatic maintenance are thought to be antagonistic piciotropic traits, but the molecular basis for this tradeoff is poorly understood. Here it is proposed that changes in protein synthesis mediate the tradeoffs that take place upon genetic and environmental manipulation in various model systems including yeast, worms, flies and mice. This hypothesis is supported by evidence that inhibition of the TOR (target of rapamycin) pathway and various translation factors that inhibit protein synthesis lead to slowing of growth and development but extend lifespan. Furthermore, dietary restriction (DR) that leads to antagonistic changes in growth and lifespan, also mediates this change by inhibiting protein synthesis. Direct screens to identify genes that extend lifespan from a subset of genes that are essential for growth and development have also uncovered a number of genes involved in protein synthesis. Given the conserved mechanisms of protein synthesis across species, I discuss potential mechanisms that mediate the lifespan extension by inhibition of protein synthesis that are likely to be important for aging and age-related disorders in humans.
生长和躯体维持被认为是拮抗的营养性状，但这种权衡的分子基础还知之甚少。本文提出，在包括酵母、蠕虫、苍蝇和老鼠在内的各种模型系统中，蛋白质合成的变化介导了遗传和环境操作所产生的权衡。这一假说得到了以下证据的支持：抑制 TOR（雷帕霉素靶蛋白）途径和各种抑制蛋白质合成的翻译因子会导致生长和发育减缓，但延长寿命。此外，导致生长和寿命产生拮抗变化的饮食限制（DR）也通过抑制蛋白质合成来介导这种变化。直接筛选以鉴定从生长和发育所必需的基因子集中延长寿命的基因，也发现了许多参与蛋白质合成的基因。鉴于蛋白质合成在物种间的保守机制，我讨论了通过抑制蛋白质合成来延长寿命的潜在机制，这些机制可能对人类的衰老和与年龄相关的疾病很重要。
