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“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.

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388

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.



已有13条评论

  1. tcya @ 2012-04-05, 09:06

    最后拿正反馈不太确定是否读懂了。投资偏向青年使40岁比本该有的身体更强壮,这时候新的一份投资可以产生比在衰老身体上更多的收益,边际收益曲线是向上的,但最终还是会向下,只不过向上段还是很长的,所以会有明显的衰老,但又不是40岁直接死了

    [回复]

    辉格 回复:

    这里的正反馈的意思是:在投资策略起作用之前,生存几率在年龄轴上有个下降分布,正是这一下降特征导致了偏向牺牲老年健康换取青年健康的投资策略,而该策略的作用将使得生存几率的年龄分布曲线变得更陡峭下行,进而使投资策略更偏向于青年,如此循环……

    [回复]

    辉格 回复:

    当然,既有系统内的任何正反馈机制都会在越过某个临界点后逆转,否则系统是不可能存续的。

    [回复]

    辉格 回复:

    生存几率的年龄分布曲线是个简化模型,更精确的模型是用“期望遗传价值”代替生存几率,因为同样的生存,健康、活力等影响繁殖能力的质量不一样,歧视性投资策略既可牺牲生存率,也可牺牲生存质量。

    [回复]

    tcya 回复:

    这条年龄分布曲线一出来,整个问题瞬间清晰无比。。

    [回复]

    tcya 回复:

    想到说这是不是意味着我们年轻时的身体、大脑……各个方面都已经趋于完美,以至于再追加投资的边际收益已经和追加到60岁老头身上的收益相等了?

    [回复]

    辉格 回复:

    不能说“完美”,只能说是均衡,边际收益相等,在体能和智力上再多投入“不合算”了。这是个亲代投资问题,其实,人类亲代投资的重点早已转向后天因素了,营养、教育、职业/婚姻机会、地位、继承权,等等。

    [回复]

    tcya 回复:

    唔,原来只想到这是个个体发育的问题,所以觉得边际收益的均衡是在年轻和年老之间,但投资到糟老头身上的回报肯定极低,所以年轻时几乎接近完美。

    [回复]

    tcya 回复:

    觉得没理解这为什么是个亲代投资的问题,文中的意思不也是从个体自身的角度考虑投资分配吗。亲代的投资确实也是基于这条收益-年龄曲线来分配的。但个体的资源和亲代的资源分配是两个过程,这两个分配最终都是在各个年龄的边际收益相等,但二者想想觉得好像又有联系,二者在各个时间点上的边际收益也会相等?想不明白

    [回复]

    辉格 回复:

    哦,是我说错了,应该这么说:身体建造与维护所需投入分为两部分,一是由亲代负担的成本,二是自身负担的成本,前者属于亲代投资,而边际收益的均衡是这两种投资的联合均衡,即,投入于自身维护投资的边际收益等于投入于子代的边际收益。

    [回复]

    辉格 回复:

    比如大脑的尺寸,它带给母亲的生育风险和儿童期营养负担,属于亲代投资,成年独立后的营养负担就是自身的维护投资。

    [回复]

    Lambert 回复:

    抱歉辉格,我看了很多遍也没看明白这段:在投资策略起作用之前,生存几率在年龄轴上有个下降分布,正是这一下降特征导致了偏向牺牲老年健康换取青年健康的投资策略,而该策略的作用将使得生存几率的年龄分布曲线变得更陡峭下行,进而使投资策略更偏向于青年。
    我不明白的是为什么青年生存率高,老年生存率低(这是我理解的下降分布)可以导致青睐提升青年健康的投资策略,从而改变生存曲线引发正反馈?
    决定投资策略的难道不应该是投资哪个阶段的边际收益最高吗?边际收益由此年龄阶段对投资的敏感性以及提升的寿命对遗传收益的增值得出,但并不和生存率有关啊。
    换句话说,不管青年生存率有多高,只要投资老年遗传受益更高,进化策略就会偏向老年人。这也是你提到的均衡吧。

    [回复]

    辉格 回复:

    哦,可能是我的说法不够清楚,我说的“生存几率在年龄轴上有个下降分布”里的生存几率,是站在个体产生时刻往后看的预期生存几率,不是在到那一刻时的预期几率。

  2. dorian_gray_ll @ 2012-10-27, 15:07

    真是一篇好文章啊…发现生物都读到shi了去…惭愧啊

    [回复]

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