Lay Summary: An evolutionary mechanism of aging was hypothesized 60 years ago to be the genetic trade-off between early life fitness and late life mortality. Genetic evidence supporting this hypothesis was unavailable then, but has accumulated recently. These tradeoffs, known as antagonistic pleiotropy, are common, perhaps ubiquitous. George Williams' 1957 paper developed the antagonistic pleiotropy hypothesis of aging, which had previously been hinted at by Peter Medawar. Antagonistic pleiotropy, as it applies to aging, hypothesizes that animals possess genes that enhance fitness early in life but diminish it in later life and that such genes can be favored by natural selection because selection is stronger early in life even as they cause the aging phenotype to emerge. No genes of the sort hypothesized by Williams were known 60 years ago, but modern molecular biology has now discovered hundreds of genes that, when their activity is enhanced, suppressed, or turned off, lengthen life and enhance health under laboratory conditions. Does this provide strong support for Williams' hypothesis? What are the implications of Williams' hypothesis for the modern goal of medically intervening to enhance and prolong human health? Here we briefly review the current state of knowledge on antagonistic pleiotropy both under wild and laboratory conditions. Overall, whenever antagonistic pleiotropy effects have been seriously investigated, they have been found. However, not all trade-offs are directly between reproduction and longevity as is often assumed. The discovery that antagonistic pleiotropy is common if not ubiquitous implies that a number of molecular mechanisms of aging may be widely shared among organisms and that these mechanisms of aging can be potentially alleviated by targeted interventions.

中文翻译：

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拮抗多效性在衰老生物学中普遍存在吗？

简单总结：60 年前，人们假设衰老的进化机制是早期生命健康与晚年死亡率之间的遗传权衡。当时还没有支持这一假设的遗传证据，但最近已经积累起来。这些权衡被称为拮抗多效性，很常见，甚至可能无处不在。乔治·威廉姆斯 (George Williams) 1957 年的论文提出了衰老的拮抗多效性假说，彼得·梅达沃 (Peter Medawar) 此前曾暗示过这一假说。拮抗多效性，当它应用于衰老时，假设动物拥有在生命早期增强健康但在以后生命中减弱的基因，并且这些基因可以受到自然选择的青睐，因为选择在生命早期更强，即使它们导致衰老表型出现。60 年前，人们还不知道威廉姆斯假设的那种基因，但现代分子生物学现在已经发现了数百种基因，当它们的活性增强、抑制或关闭时，它们在实验室条件下可以延长寿命并增强健康。这是否为威廉姆斯的假设提供了强有力的支持？威廉姆斯的假设对于通过医学干预来增强和延长人类健康的现代目标有何影响？在这里，我们简要回顾一下野生和实验室条件下拮抗多效性的知识现状。总的来说，每当认真研究拮抗多效性效应时，就会发现它们。然而，并非所有的权衡都像人们通常假设的那样直接在繁殖和寿命之间进行。拮抗性多效性即使不是普遍存在，也是常见的这一发现意味着，许多衰老的分子机制可能在生物体之间广泛共享，并且这些衰老机制可以通过有针对性的干预措施来缓解。