PDF(Pubmed)
Abstract：
Mice with genetic growth hormone (GH) deficiency or GH resistance live much longer than their normal siblings maintained under identical conditions with unlimited access to food. Extended longevity of these mutants is associated with extension of their healthspan (period of life free of disability and disease) and with delayed and/or slower aging. Importantly, GH and GH-related traits have been linked to the regulation of aging and longevity also in mice that have not been genetically altered and in other mammalian species including humans. Avai+lable evidence indicates that the impact of suppressed GH signaling on aging is mediated by multiple interacting mechanisms and involves trade-offs among growth, reproduction, and longevity. Life history traits of long-lived GH-related mutants include slow postnatal growth, delayed sexual maturation, and reduced fecundity (smaller litter size and increased intervals between the litters). These traits are consistent with a slower pace-of-life, a well-documented characteristic of species of wild animals that are long-lived in their natural environment. Apparently, slower pace-of-life (or at least some of its features) is associated with extended longevity both within and between species. This association is unexpected and may appear counterintuitive, because the relationships between adult body size (a GH-dependent trait) and longevity within and between species are opposite rather than similar. Studies of energy metabolism and nutrient-dependent signaling pathways at different stages of the life course will be needed to elucidate mechanisms of these relationships.
摘要：
具有遗传生长激素（GH）缺乏症或GH抗性的小鼠的寿命比在相同条件下保持的正常兄弟姐妹长得多，并且可以无限获取食物。这些突变体的延长寿命与它们的健康寿命(无残疾和疾病的寿命)的延长以及延迟和/或较慢的衰老相关。重要的是,GH和GH相关的性状与衰老和寿命的调节有关，在没有遗传改变的小鼠和包括人类在内的其他哺乳动物物种中也是如此。Avai+lable证据表明，抑制GH信号对衰老的影响是由多种相互作用机制介导的，并涉及生长之间的权衡，繁殖，和长寿。长寿GH相关突变体的生活史特征包括出生后生长缓慢，性成熟延迟,减少繁殖力（产仔数较小，产仔数间隔增加）。这些特征与较慢的生活节奏一致，在自然环境中长期生存的野生动物物种的一种有据可查的特征。显然,较慢的生活节奏（或至少其某些特征）与物种内部和物种之间的寿命延长有关。这种关联是出乎意料的，可能看起来违反直觉，因为物种内部和物种之间的成年体型（GH依赖性性状）与寿命之间的关系是相反的，而不是相似的。需要对生命历程不同阶段的能量代谢和营养依赖性信号通路进行研究，以阐明这些关系的机制。
