含有〈衰老〉标签的文章(1)

衰老和死亡的进化机制

小手问道:“死亡算完全由基因控制的吗?算不算phenotype?”

全年无休认为:“绝大部分的死亡都并不是整个机体的走到终点那样的死亡,而是某个器官由于外界影响导致功能丧失后的死亡。”

DNA解释道:

死亡是由于“错误”和“损伤”积累造成的。因为细胞在复制过程中,其机制只能勉强保持一个正确率,使得生命体凑活着能活着。但是细胞每分裂一次,就积累一些“错误”和“损伤”,由此导致衰老。这些“错误”和“损伤”积累到一定程度,不再能维持生命体,就是死亡。事实上,基因控制了许多“防止死亡”的程序,只可惜基因的“控制力”不够,无力避免最终的消亡。紫外线、自由基、致癌物质都是加速“错误”和“(more...)

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小手问道:“死亡算完全由基因控制的吗?算不算phenotype?”

全年无休认为:“绝大部分的死亡都并不是整个机体的走到终点那样的死亡,而是某个器官由于外界影响导致功能丧失后的死亡。”

DNA解释道:

死亡是由于“错误”和“损伤”积累造成的。因为细胞在复制过程中,其机制只能勉强保持一个正确率,使得生命体凑活着能活着。但是细胞每分裂一次,就积累一些“错误”和“损伤”,由此导致衰老。这些“错误”和“损伤”积累到一定程度,不再能维持生命体,就是死亡。事实上,基因控制了许多“防止死亡”的程序,只可惜基因的“控制力”不够,无力避免最终的消亡。紫外线、自由基、致癌物质都是加速“错误”和“损伤”积累的东西。

DNA的解释是对的,但可能只解释了衰老机制的一小部分,如果只考虑这一点,我们的衰老过程会大不一样,最近读到Steven Pinker引述了George Williams的一种解释,非常精彩,简单的说:基因组在维护人体健康的投资策略上,严重偏向于早期阶段,而不惜以牺牲后期健康为代价。

首先,即使我们不考虑衰老,只考虑被雷劈死被老虎吃掉这种风险,人活到40岁的概率,和活到60岁的概率,仍是大不相同的。

如DNA所说,因为细胞分裂等环节的积累错误,人体需要不断维护才能继续生存,然而维护是有成本的;这样,当面临选择:两种维护措施分别可将40岁人和60岁人的死亡风险分别降低20%,而成本相同,那么,理性的选择便是前一种,因为对60岁人的健康投入,只有在能活到60岁的条件下才可能获得回报,而对40岁人的健康投入,则对所有活到40岁的人都可获得回报,因而回报率是显著不同的。

同理,当一种维护措施以提高60岁人死亡风险20%为代价,而降低40岁人死亡风险20%为收益时,这笔投资是合算的,反之,牺牲40岁人健康而换取60岁人健康的投资,必须达到高得多的收益比,才是合算的。结果就是:基因组倾向于以牺牲老年健康为代价换取青年健康。

这一机制的关键在于(这一点Williams好像没指出,但我认为是极端重要的),其中包含了正反馈:投资预期回报的最初差异,导致投资偏向青年,而这种偏向又扩大了回报差异,于是导致更严重的投资偏向,结果我们看到,在越过一个临界点后,衰老过程十分迅速。

以下文字摘自Steven Pinker: The Language Instinct, p295:

Even if there is some utility to our learning a second language as adults, the critical period for language acquisition may have evolved as part of a larger fact of life: the increasing feebleness and vulnerability with advancing age that biologists call "senescence." Common sense says that the body, like all machines, must wear out with use, but this is another misleading implication of the appliance metaphor.

Organisms are self-replenishing, self-repairing systems, and there is no physical reason why we should not be biologically immortal, as in fact lineages of cancer cells used in laboratory research are. That would not mean that we would actually be immortal. Every day there is a certain probability that we will fall off a cliff, catch a virulent disease, be struck by lightning, or be murdered by a rival, and sooner or later one of those lightning bolts or bullets will have our name on it. The question is, is every day a lottery in which the odds of drawing a fatal ticket are the same, or do the odds get worse and worse the longer we play? Senescence is the bad news that the odds do change; elderly people are killed by falls and flus that their grandchildren easily survive. A major question in modern evolutionary biology is why this should be true, given that selection operates at every point of an organism's life history. Why aren't we built to be equally hale and hearty every day of our lives, so that we can pump out copies of ourselves indefinitely?

The solution, from George Williams and P. B. Medawar, is ingenious. As natural selection designed organisms, it must have been faced with countless choices among features that involved different tradeoffs of costs and benefits at different ages. Some materials might be strong and light but wear out quickly, whereas others might be heavier but more durable. Some biochemical processes might deliver excellent products but leave a legacy of accumulating pollution within the body. There might be a metabolically expensive cellular repair mechanism that comes in most useful late in life when wear and tear have accumulated. What does natural selection do when faced with these tradeoffs?
In general, it will favor an option with benefits to the young organism and costs to the old one over an option with the same average benefit spread out evenly over the life span. This asymmetry is rooted in the inherent asymmetry of death. If a lightning bolt kills a forty-year-old, there will be no fifty-year-old or sixty-year-old to worry about, but there will have been a twenty-year-old and a thirty-year-old. Any bodily feature designed for the benefit of the potential over-forty incarnations, at the expense of the under-forty incarnations, will have gone to waste. And the logic is the same for unforeseeable death at any age: the brute mathematical fact is that all things being equal, there is a better chance of being a young person than being an old person. So genes that strengthen young organisms at the expense of old organisms have the odds in their favor and will tend to accumulate over evolutionary timespans, whatever the bodily system, and the result is overall senescence.