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衰老和CO2的保护作用

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http://raypeat.com/articles/articles/protective-co2-aging.shtml

The therapeutic effects of increasing carbon dioxide are being more widely recognized in recent years. Even Jane Brody, the NY Times writer on health topics, has favorably mentioned the use of the Buteyko method for asthma, and the idea of “permissive hypercapnia” during mechanical ventilation, to prevent lung damage from excess oxygen, has been discussed in medical journals. But still very few biologists recognize its role as a fundamental, universal protective factor. I think it will be helpful to consider some of the ways carbon dioxide might be controlling situations that otherwise are poorly understood. 近年来,增加二氧化碳的治疗效果得到了更广泛的认可。甚至《纽约时报》健康主题作家简·布罗迪 (Jane Brody) 也积极提到了使用 Buteyko 方法治疗哮喘,并且在医学期刊上讨论了机械通气期间“允许性高碳酸血症”以防止肺因氧气过多而受损的想法. 但是仍然很少有生物学家认识到它作为一个基本的、普遍的保护因素的作用。我认为考虑二氧化碳可能控制的情况的一些方式会有所帮助,否则人们对其知之甚少。

The brain has a high rate of oxidative metabolism, and so it forms a very large proportion of the carbon dioxide produced by an organism. It also governs, to a great extent, the metabolism of other tissues, including their consumption of oxygen and production of carbon dioxide or lactic acid. Within a particular species, the rate of oxygen consumption increases in proportion to brain size, rather than body weight. Between very different species, the role of the brain in metabolism is even more obvious, since the resting metabolic rate corresponds to the size of the brain. For example, a cat’s brain is about the size of a crocodile’s, and their oxygen consumption at rest is similar, despite their tremendous difference in body size. 大脑具有很高的氧化代谢率,因此它在生物体产生的二氧化碳中占很大比例。它还在很大程度上控制着其他组织的新陈代谢,包括它们对氧气的消耗和二氧化碳或乳酸的产生。在特定物种中,耗氧量的增加与大脑大小成正比,而不是与体重成正比。在非常不同的物种之间,大脑在新陈代谢中的作用更加明显,因为静息代谢率与大脑的大小相对应。例如,猫的大脑和鳄鱼的大脑差不多大,它们在休息时的耗氧量是相似的,尽管它们的体型差异很大。

Stress has to be understood as a process that develops in time, and the brain (especially the neocortex and the frontal lobes) organizes the adaptive and developmental processes in both the spatial and temporal dimensions. The meaning of a situation influences the way the organism responds. For example, the stress of being restrained for a long time can cause major gastrointestinal bleeding and ulcerization, but if the animal has the opportunity to bite something during the stress (signifying its ability to fight back, and the possibility of escape) it can avoid the stress ulcers. 压力必须被理解为一个随时间发展的过程,大脑(尤其是新皮质和额叶)在空间和时间维度上组织适应和发展过程。情境的意义会影响有机体的反应方式。例如,长时间被束缚的压力会导致胃肠道大出血和溃疡,但如果动物在压力期间有机会咬东西(表示它有反击的能力,以及逃跑的可能性),它可以避免应激性溃疡

The patterning of the nervous activity throughout the body governs the local ability to produce carbon dioxide. When the cortex of the brain is damaged or removed, an animal becomes rigid, so the cortex is considered to have a “tonic inhibitory action” on the body. But when the nerves are removed from a muscle (for example, by disease or accident), the muscle goes into a state of constant activity, and its ability to oxidize glucose and produce carbon dioxide is reduced, while its oxidation of fatty acids persists, increasing the production of toxic oxidative fragments of the fatty acids, which contributes to the muscle’s atrophy. 全身神经活动的模式控制着局部产生二氧化碳的能力。当大脑皮层受损或被切除时,动物会变得僵硬,因此皮层被认为对身体有“强直抑制作用”。但是当神经从肌肉中移除时(例如,由于疾病或意外),肌肉进入持续活动状态,其氧化葡萄糖和产生二氧化碳的能力降低,而脂肪酸的氧化持续存在,增加脂肪酸的有毒氧化片段的产生,这会导致肌肉萎缩

The organism’s intentions, expectations, or plans, are represented in the nervous system as a greater readiness for action, and in the organs and tissues controlled by the nerves, as an increase or decrease of oxidative efficiency, analogous to the differences between innervated and denervated muscles. This pattern in the nervous system has been called “the acceptor of action,” because it is continually being compared with the actual situation, and being refined as the situation is evaluated. The state of the organism, under the influence of a particular acceptor of action, is called a “functional system,” including all the components of the organism that participate most directly in realizing the intended adaptive action. 生物体的意图、期望或计划在神经系统中表现为对行动的更大准备,在神经控制的器官和组织中表现为氧化效率的增加或减少,类似于神经支配和去神经支配之间的差异肌肉。神经系统中的这种模式被称为“行动的接受者”,因为它不断地与实际情况进行比较,并随着情况的评估而不断完善。生物体在特定动作受体的影响下的状态称为“功能系统”,包括生物体中最直接参与实现预期适应性动作的所有组件。

The actions of nerves can be considered anabolic, because during a stressful situation in which the catabolic hormones of adaption, e.g., cortisol, increase, the tissues of the functional system are protected, and while idle tissues may undergo autophagy or other form of involution, the needs of the active tissues are supplied with nutrients from their breakdown, allowing them to change and, when necessary, grow in size or complexity. 神经的作用可以被认为是合成代谢的,因为在压力情况下,适应的分解代谢激素(例如皮质醇)增加,功能系统的组织受到保护,而闲置的组织可能会经历自噬或其他形式的退化,活动组织的需要从它们的分解中获得营养,使它们能够改变,并在必要时增加大小或复杂性。

The brain’s role in protecting against injury by stress, when it sees a course of action, has a parallel in the differences between concentric (positive, muscle shortening) and eccentric (negative, lengthening under tension) exercise, and also with the differences between innervated and denervated muscles. In eccentric exercise and denervation, less oxygen is used and less carbon dioxide is produced, while lactic acid increases, displacing carbon dioxide, and more fat is oxidized. Prolonged stress similarly decreases carbon dioxide and increases lactate, while increasing the use of fat. 当大脑看到一个动作过程时,它在防止压力伤害方面的作用与向心运动(积极,肌肉缩短)和离心运动(消极,在紧张状态下延长)之间的差异相似,也与受神经支配之间的差异相似。和去神经支配的肌肉。在离心运动和去神经支配中,使用更少的氧气,产生更少的二氧化碳,而乳酸增加,取代二氧化碳,更多的脂肪被氧化。长时间的压力同样会减少二氧化碳并增加乳酸,同时增加脂肪的使用

Darkness is stressful and catabolic. For example, in aging people, the morning urine contains nearly all of the calcium lost during the 24 hour period, and mitochondria are especially sensitive to the destructive effects of darkness. Sleep reduces the destructive catabolic effects of darkness. During the rapid-eye-movement (dreaming) phase of sleep, breathing is inhibited, and the level of carbon dioxide in the tissues accumulates. In restful sleep, the oxygen tension is frequently low enough, and the carbon dioxide tension high enough, to trigger the multiplication of stem cells and mitochondria. 黑暗是压力和分解代谢。例如,在老年人中,晨尿中几乎包含了 24 小时内丢失的所有钙,而线粒体对黑暗的破坏作用特别敏感。睡眠减少了黑暗的破坏性分解代谢作用。在睡眠的快速眼动(做梦)阶段,呼吸受到抑制,组织中的二氧化碳水平会积聚。在宁静的睡眠中,氧气张力通常足够低,二氧化碳张力足够高,以触发干细胞和线粒体的增殖。

Dreams represent the “acceptor of action” operating independently of the sensory information that it normally interacts with. During dreams, the brain (using a system called the Ascending Reticular Activating System) disconnects itself from the sensory systems. I think this is the nervous equivalent of concentric/positive muscle activity, in the sense that the brain is in control of its actions. The active, dreaming phase of sleep occurs more frequently in the later part of the night, as morning approaches. This is the more stressful part of the night, with cortisol and some other stress hormones reaching a peak at dawn, so it would be reasonable for the brain’s defensive processes to be most active at that time. The dreaming process in the brain is associated with deep muscle relaxation, which is probably associated with the trophic (restorative) actions of the nerves. 梦代表“行动的接受者”,独立于它通常与之交互的感官信息而运作。在做梦时,大脑(使用称为上升网状激活系统的系统)将自己与感觉系统断开。我认为这是同心/正肌肉活动的神经等价物,因为大脑控制着它的动作。随着早晨的临近,睡眠的活跃、做梦阶段更频繁地发生在深夜。这是夜晚压力更大的部分,皮质醇和其他一些压力荷尔蒙在黎明时达到峰值,因此大脑的防御过程在那个时候最活跃是合理的。大脑中的做梦过程与深度肌肉放松有关

In ancient China the Taoists were concerned with longevity, and according to Joseph Needham (Science and Civilization in China) their methods included the use of herbs, minerals, and steroids extracted from the urine of children. Some of those who claimed extreme longevity practiced controlled breathing and tai chi (involving imagery, movement, and breating), typically in the early morning hours, when stress reduction is most important. As far as I know, there are no studies of carbon dioxide levels in practitioners of tai chi, but the sensation of warmth they typically report suggests that it involves hypoventilation. 在古代中国,道家关注长寿,根据约瑟夫·尼达姆(中国科学与文明)的说法,他们的方法包括使用从儿童尿液中提取的草药、矿物质和类固醇。一些声称极长寿的人通常在清晨练习控制呼吸和太极拳(包括意象、运动和呼吸),此时减压最为重要。据我所知,没有关于太极拳练习者二氧化碳水平的研究,但他们通常报告的温暖感觉表明这与通气不足有关。

In the 1960s, a Russian researcher examined hospital records of measurements of newborn babies, and found that for several decades the size of their heads had been increasing. He suggested that it might be the result of increasing atmospheric carbon dioxide. 1960 年代,一位俄罗斯研究人员检查了医院新生儿测量记录,发现几十年来他们的头部尺寸一直在增加。他认为这可能是大气中二氧化碳增加的结果。

The experiences and nutrition of a pregnant animal are known to affect the expression of genes in the offspring, affecting such things as allergies, metabolic rate, brain size, and intelligence. Miles Storfer (1999) has reviewed the evidence for epigenetic environmental control of brain size and intelligence. The main mechanisms of epigenetic effects or “imprinting” are now known to involve methylation and acetylation of the chromosomes (DNA and histones). 众所周知,怀孕动物的经历和营养会影响后代基因的表达,影响过敏、代谢率、大脑大小和智力等因素。Miles Storfer (1999) 回顾了大脑大小和智力的表观遗传环境控制的证据。现在已知表观遗传效应或“印记”的主要机制涉及染色体(DNA 和组蛋白)的甲基化和乙酰化。

Certain kinds of behavior, as well as nutrition and other environmental factors, increase the production and retention of carbon dioxide. The normal intrauterine level of carbon dioxide is high, and it can be increased or decreased by changes in the mother’s physiology. The effects of carbon dioxide on many biological processes involving methylation and acetylation of the genetic material suggest that the concentration of carbon dioxide during gestation might regulate the degree to which parental imprinting will persist in the developing fetus. There is some evidence of increased demethylation associated with the low level of oxygen in the uterus (Wellman, et al., 2008). A high metabolic rate and production of carbon dioxide would increase the adaptability of the new organism, by decreasing the limiting genetic imprints. 某些行为以及营养和其他环境因素会增加二氧化碳的产生和滞留。正常宫内二氧化碳水平较高,可随母亲生理变化而升高或降低。二氧化碳对许多涉及遗传物质甲基化和乙酰化的生物过程的影响表明,妊娠期间二氧化碳的浓度可能会调节父母印记在发育中的胎儿中持续存在的程度。有一些证据表明,子宫内的低氧水平会导致去甲基化增加(Wellman 等,2008)。高代谢率和二氧化碳的产生将通过减少限制性遗传印记来提高新生物的适应性。

A quick reduction of carbon dioxide caused by hyperventilation can provoke an epileptic seizure, and can increase muscle spasms and vascular leakiness, and (by releasing serotonin and histamine) contribute to inflammation and clotting disorders. On a slightly longer time scale, a reduction of carbon dioxide can increase the production of lactic acid, which is a promoter of inflammation and fibrosis. A prolonged decrease in carbon dioxide can increase the susceptibility of proteins to glycation (the addition of aldehydes, from polyunsaturated fat peroxidation or methylglyoxal from lactate metabolism, to amino groups), and a similar process is likely to contribute to the methylation of histones, a process that increases with aging. Histones regulate genetic activity. 过度换气引起的二氧化碳快速减少会引发癫痫发作,并会增加肌肉痉挛和血管渗漏,并且(通过释放血清素和组胺)导致炎症和凝血障碍。在稍长的时间尺度上,二氧化碳的减少可以增加乳酸的产生,乳酸是炎症和纤维化的促进剂。二氧化碳的长期减少会增加蛋白质对糖化的敏感性(添加醛,来自多不饱和脂肪过氧化或来自乳酸代谢的甲基乙二醛,到氨基),类似的过程可能有助于组蛋白的甲基化,随着年龄增长而增加的过程。组蛋白调节遗传活动。

With aging, DNA methylation is increased (Bork, et al., 2009). I suggest that methylation stabilizes and protects cells when growth and regeneration aren’t possible (and that it’s likely to increase when CO2 isn’t available). Hibernation (Morin and Storey, 2009) and sporulation (Ruiz-Herrera, 1994; Clancy, et al., 2002) appear to use methylation protectively. Parental stress, prenatal stress, early life stress, and even stress in adulthood contribute to “imprinting of the genes,” partly through methylation of DNA and the histones. 随着衰老,DNA 甲基化增加(Bork 等,2009)。我认为甲基化可以在无法生长和再生的情况下稳定并保护细胞(如果没有二氧化碳,甲基化可能会增加)。冬眠(Morin 和 Storey,2009)和孢子形成(Ruiz-Herrera,1994;Clancy 等,2002)似乎保护性地使用甲基化。 父母压力、产前压力、早期生活压力,甚至成年期压力都会导致“基因印记”,部分原因是 DNA 和组蛋白的甲基化。

Methionine and choline are the main dietary sources of methyl donors. Restriction of methionine has many protective effects, including increased average (42%) and maximum (44%) longevity in rats (Richie, et al., 1994). Restriction of methyl donors causes demethylation of DNA (Epner, 2001). The age accelerating effect of methionine might be related to disturbing the methylation balance, inappropriately suppressing cellular activity. Besides its effect on the methyl pool, methionine inhibits thyroid function and damages mitochondria. 甲硫氨酸和胆碱是甲基供体的主要膳食来源。限制甲硫氨酸具有许多保护作用,包括增加大鼠的平均寿命 (42%) 和最大寿命 (44%) (Richie, et al., 1994)。甲基供体的限制导致 DNA 去甲基化 (Epner, 2001)。蛋氨酸的衰老加速作用可能与扰乱甲基化平衡、不当抑制细胞活性有关。除了对甲基池的影响外,蛋氨酸还会抑制甲状腺功能并破坏线粒体。

The local concentration of carbon dioxide in specific tissues and organs can be adjusted by nervous and hormonal activation or inhibition of the carbonic anhydrase enzymes, that accelerate the oonversion of CO2 to carbonic acid, H2CO3. The activity of carbonic anhydrase can determine the density and strength of the skeleton, the excitability of nerves, the accumulation of water, and can regulate the structure and function of the tissues and organs. Ordinarily, carbon dioxide and bicarbonate are thought of only in relation to the regulation of pH, and only in a very general way. Because of the importance of keeping the pH of the blood within a narrow range, carbon dioxide is commonly thought of as a toxin, because an excess can cause unconsciousness and acidosis. But increasing carbon dioxide doesn’t necessarily cause acidosis, and acidosis caused by carbon dioxide isn’t as harmful as lactic acidosis. 特定组织和器官中二氧化碳的局部浓度可以通过神经和激素的激活或碳酸酐酶的抑制来调节,从而加速 CO2 转化为碳酸 H2CO3。碳酸酐酶的活性可以决定骨骼的密度和强度,神经的兴奋性,水分的积累,可以调节组织器官的结构和功能。 通常,二氧化碳和碳酸氢盐被认为仅与 pH 值的调节有关,而且只是以非常普遍的方式。由于将血液的 pH 值保持在一个狭窄的范围内很重要,二氧化碳通常被认为是一种毒素,因为过量会导致失去知觉和酸中毒。但是增加二氧化碳并不一定会引起酸中毒,而且二氧化碳引起的酸中毒不像乳酸酸中毒那样有害。

Frogs and toads, being amphibians, are especially dependent on water, and in deserts or areas with a dry season they can survive a prolonged dry period by burrowing into mud or sand. Since they may be buried 10 or 11 inches below the surface, they are rarely found, and so haven’t been extensively studied. In species that live in the California desert, they have been known to survive 5 years of burial without rainfall, despite a moderately warm average temperature of their surroundings. One of their known adaptations is to produce a high level of urea, allowing them to osmotically absorb and retain water. (Very old people sometimes have extremely high urea and osmotic tension.) 青蛙和蟾蜍是两栖动物,特别依赖水,在沙漠或旱季地区,它们可以通过在泥土或沙子中挖洞来度过长时间的干旱期。由于它们可能被埋在地表以下 10 或 11 英寸处,因此很少被发现,因此没有被广泛研究。众所周知,生活在加利福尼亚沙漠中的物种可以在没有降雨的情况下埋葬 5 年,尽管周围环境的平均温度适中。它们已知的适应性之一是产生高水平的尿素,使它们能够渗透吸收和保留水分。(非常老的人有时会有极高的尿素和渗透压。)

Some laboratory studies show that as a toad burrows into mud, the amount of carbon dioxide in its tissues increases. Their skin normally functions like a lung, exchanging oxygen for carbon dioxide. If the toad’s nostrils are at the surface of the mud, as dormancy begins its breathing will gradually slow, increasing the carbon dioxide even more. Despite the increasing carbon dioxide, the pH is kept stable by an increase of bicarbonate (Boutilier, et al., 1979). A similar increase of bicarbonate has been observed in hibernating hamsters and doormice. Thinking about the long dormancy of frogs reminded me of a newspaper story I read in the 1950s. Workers breaking up an old concrete structure found a dormant toad enclosed in the concrete, and it revived soon after being released. The concrete had been poured decades earlier. 一些实验室研究表明,当蟾蜍钻入泥中时,其组织中的二氧化碳含量会增加。他们的皮肤通常像肺一样发挥作用,将氧气交换为二氧化碳。如果蟾蜍的鼻孔在泥的表面,随着休眠的开始,它的呼吸会逐渐减慢,从而增加更多的二氧化碳。尽管二氧化碳增加,但碳酸氢盐的增加使 pH 值保持稳定(Boutilier, et al., 1979)。在冬眠的仓鼠和门鼠中观察到碳酸氢盐的类似增加。 想到青蛙的长期休眠,我想起了 1950 年代读到的一篇报纸报道。拆除旧混凝土结构的工人在混凝土中发现了一只休眠的蟾蜍,它在被释放后很快就复活了。混凝土是几十年前浇筑的。

Although systematic study of frogs or toads during their natural buried estivation has been very limited, there have been many reports of accidental discoveries that suggest that the dormant state might be extended indefinitely if conditions are favorable. Carbon dioxide has antioxidant effects, and many other stabilizing actions, including protection against hypoxia and the excitatory effects of intracellular calcium and inflammation (Baev, et al., 1978, 1995; Bari, et al., 1996; Brzecka, 2007; Kogan, et al., 1994; Malyshev, et al., 1995). 尽管对青蛙或蟾蜍在自然埋藏期间的系统研究非常有限,但有许多意外发现的报告表明,如果条件有利,休眠状态可能会无限期延长。二氧化碳具有抗氧化作用和许多其他稳定作用,包括防止缺氧以及细胞内钙和炎症的兴奋作用(Baev 等人,1978 年、1995 年;Bari 等人,1996 年;Brzecka,2007 年;Kogan,等人,1994 年;Malyshev 等人,1995 年)。

When mitochondria are “uncoupled,” they produce more carbon dioxide than normal, and the mitochondria produce fewer free radicals. Animals with uncoupled mitochondria live longer than animals with the ordinary, more efficient mitochondria, that produce more reactive oxidative fragments. One effect of the high rate of oxidation of the uncoupled mitochondria is that they can eliminate polyunsatured fatty acids that might otherwise be integrated into tissue structures, or function as inappropriate regulatory signals. 当线粒体“解偶联”时,它们会产生比正常情况更多的二氧化碳,而线粒体产生的自由基更少。线粒体未偶联的动物比普通线粒体的动物寿命更长,更有效的线粒体产生更多的活性氧化片段。未偶联线粒体的高氧化率的一个影响是它们可以消除多不饱和脂肪酸,否则这些脂肪酸可能会被整合到组织结构中,或者作为不适当的调节信号起作用。

Birds have a higher metabolic rate than mammals of the same size, and live longer. Their tissues contain fewer of the highly unsaturated fatty acids. Queen bees, which live many times longer than worker bees, have mainly monounsaturated fats in their tissues, while the tissues of the short-lived worker bees, receiving a different diet, within a couple of weeks of hatching will contain highly unsaturated fats. 鸟类的新陈代谢率高于同等大小的哺乳动物,寿命也更长。他们的组织含有较少的高度不饱和脂肪酸。蜂王的寿命比工蜂长许多倍,它们的组织中主要含有单不饱和脂肪,而短命工蜂的组织在接受不同的饮食后,在孵化后的几周内将含有高度不饱和脂肪。

Bats have a very high metabolic rate, and an extremely long lifespan for an animal of their size. While most animals of their small size live only a few years, many bats live a few decades. Bat caves usually have slightly more carbon dioxide than the outside atmosphere, but they usually contain a large amount of ammonia, and bats maintain a high serum level of carbon dioxide, which protects them from the otherwise toxic effects of the ammonia. 蝙蝠具有非常高的代谢率,并且对于它们这种体型的动物来说寿命非常长。虽然大多数体型较小的动物只能活几年,但许多蝙蝠却能活几十年。蝙蝠洞穴中的二氧化碳通常比外部大气略多,但它们通常含有大量的氨,而且蝙蝠的血清二氧化碳水平很高,这可以保护它们免受氨的其他毒性影响。

The naked mole rat, another small animal with an extremely long lifespan (in captivity they have lived up to 30 years, 9 or 10 times longer than mice of the same size) has a low basal metabolic rate, but I think measurements made in laboratories might not represent their metabolic rate in their natural habitat. They live in burrows that are kept closed, so the percentage of oxygen is lower than in the outside air, and the percentage of carbon dioxide ranges from 0.2% to 5% (atmospheric CO2 is about 0.038). The temperature and humidity in their burrows can be extremely high, and to be very meaningful their metabolic rate would have to be measured when their body temperature is raised by the heat in the burrow. 裸鼹鼠,另一种寿命极长的小动物(圈养时它们的寿命长达 30 年,比同等大小的老鼠长 9 或 10 倍)的基础代谢率较低,但我认为在实验室进行的测量可能不代表它们在自然栖息地的代谢率。它们生活在封闭的洞穴中,因此氧气的百分比低于外部空气中的百分比,二氧化碳的百分比在 0.2% 到 5% 之间(大气 CO2 约为 0.038)。它们的洞穴中的温度和湿度可能非常高,要使它们的新陈代谢率变得非常有意义,就必须在它们的体温因洞穴中的热量而升高时进行测量。

When they have been studied in Europe and the US, there has been no investigation of the effect of altitude on their metabolism, and these animals are native to the high plains of Kenya and Ethiopia, where the low atmospheric pressure would be likely to increase the level of carbon dioxide in their tissues. Consequently, I doubt that the longevity seen in laboratory situations accurately reflects the longevity of the animals in their normal habitat. 在欧洲和美国研究它们时,没有调查海拔对其新陈代谢的影响,这些动物原产于肯尼亚和埃塞俄比亚的高平原,那里的低气压可能会增加他们组织中的二氧化碳水平。因此,我怀疑在实验室情况下看到的寿命是否准确地反映了动物在其正常栖息地中的寿命。

Besides living in a closed space with a high carbon dioxide content, mole rats have another similarity to bees. In each colony, there is only one female that reproduces, the queen, and, like a queen bee, she is the largest individual in the colony. In beehives, the workers carefully regulate the carbon dioxide concentration, which varies from about 0.2% to 6%, similar to that of the mole rat colony. A high carbon dioxide content activates the ovaries of a queen bee, increasing her fertility. 除了生活在二氧化碳含量高的封闭空间外,鼹鼠还有一个与蜜蜂相似的地方。在每个蜂群中,只有一个雌性会繁殖,即蜂王,并且像蜂王一样,她是蜂群中最大的个体。在蜂箱中,工人们小心地调节二氧化碳浓度,从大约 0.2% 到 6% 不等,类似于鼹鼠群体。高二氧化碳含量会激活蜂王的卵巢,提高她的生育能力。

Since queen bees and mole rats live in the dark, I think their high carbon dioxide compensates for the lack of light. (Both light and CO2 help to maintain oxidative metabolism and inhibit lactic acid formation.) Mole rats are believed to sleep very little. During the night, normal people tolerate more CO2, and so breathe less, especially near morning, with increased active dreaming sleep. 由于蜂王和鼹鼠生活在黑暗中,我认为它们的高二氧化碳补偿了光线的缺乏。(光和二氧化碳都有助于维持氧化代谢并抑制乳酸形成。)据信鼹鼠的睡眠时间很少。在夜间,正常人可以耐受更多的二氧化碳,因此呼吸会减少,尤其是在接近早晨时,会增加活跃的做梦睡眠。

A mole rat has never been known to develop cancer. Their serum C-reactive protein is extremely low, indicating that they are resistant to inflammation. In humans and other animals that are susceptible to cancer, one of the genes that is likely to be silenced by stress, aging, and methylation is p53, a tumor-suppressor gene. 从未有人知道鼹鼠会患上癌症。他们的血清C反应蛋白极低,表明他们对炎症有抵抗力。在人类和其他易患癌症的动物中,可能因压力、衰老和甲基化而沉默的基因之一是 p53,一种肿瘤抑制基因。

If the intrauterine experience, with low oxygen and high carbon dioxide, serves to “reprogram” cells to remove the accumulated effects of age and stress, and so to maximize the developmental potential of the new organism, a life that’s lived with nearly those levels of oxygen and carbon dioxide might be able to avoid the progressive silencing of genes and loss of function that cause aging and degenerative diseases. 如果低氧和高二氧化碳的宫内经历有助于“重新编程”细胞以消除年龄和压力的累积影响,从而最大限度地发挥新生物的发育潜力氧气和二氧化碳可能能够避免导致衰老和退行性疾病的基因逐渐沉默和功能丧失。

Several diseases and syndromes are now thought to involve abnormal methylation of genes. Prader-Willi sydrome, Angelman’s syndrome, and various “autistic spectrum disorders,” as well as post-traumatic stress disorder and several kinds of cancer seem to involve excess methylation. 现在认为几种疾病和综合征与基因的异常甲基化有关。Prader-Willi 综合征、Angelman 综合征和各种“自闭症谱系障碍”,以及创伤后应激障碍和几种癌症似乎都与过度甲基化有关。

Moderate methionine restriction (for example, using gelatin regularly in the diet) might be practical, but if increased carbon dioxide can activate the demethylase enzymes in a controlled way, it might be a useful treatment for the degenerative diseases and for aging itself. The low carbon dioxide production of hypothyroidism (e.g., Lee and Levine, 1999), and the respiratory alkalosis of estrogen excess, are often overlooked. An adequate supply of calcium, and sometimes supplementation of salt and baking soda, can increase the tissue content of CO2. 适度限制蛋氨酸(例如,在饮食中定期使用明胶)可能是实用的,但如果增加的二氧化碳可以以受控方式激活脱甲基酶,则它可能是治疗退行性疾病和衰老本身的有用方法。 甲状腺功能减退症的二氧化碳产量低(例如,Lee 和 Levine,1999)以及雌激素过量引起的呼吸性碱中毒,常常被忽视。充足的钙供应,有时补充盐和小苏打,可以增加组织中二氧化碳的含量。

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