How and why we age
How and why we age
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DOI：
10.1016/s0531-5565(98)00023-0
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发表时间：
1998-11-01
影响因子：
3.9
通讯作者：
Hayflick, L
中科院分区：
文献类型：
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作者：
Hayflick, L
在完成了从受孕到出生，然后到性成熟和成年的奇迹之后，自然选择无法支持一种更基本的机制的发展，这种机制将永远保持那些早期的奇迹。这种失败的表现被称为衰老。因为野生动物很少会衰老，所以进化不可能支持年龄变化的遗传程序。自然选择有利于那些最有可能通过发展更好的生存策略和生命系统中更大的储备能力来更好地逃避捕食，疾病，事故和极端环境而获得繁殖成功的动物。自然选择在繁殖成功后减少，因为物种不会从更长寿的成员中受益。生殖成熟后剩余的生理储备水平决定寿命，并伴随着作用于早期发育事件的选择过程而进化。生理储备的更新速度与损失速度不一样，因为分子紊乱的增长速度大于修复能力的增长速度。这些都是年龄的变化，它们增加了对捕食、事故或疾病的脆弱性。未能区分衰老和疾病不仅模糊了我们理解衰老的基本生物学的努力，而且它具有深刻的政治和经济后果，危及老年医学领域。疾病引起的变化或病理变化至少可以从四个重要原因中与年龄变化区分开来。与任何已知的疾病不同，（1）只要有足够的时间，每个人都会发生年龄变化，（2）年龄变化几乎跨越所有物种的障碍，（3）没有疾病只会在繁殖成功的年龄之后折磨一个物种的所有成员，（4）衰老发生在所有受人类保护的野生动物身上，即使该物种可能已经数千年或数百万年没有经历衰老。解决与年龄有关的疾病不会提高我们对衰老的认识，就像解决儿童疾病不会提高我们对儿童发育的认识一样。我们没有传达这样一个信息，即必须对一个很少提出的问题给予更大的支持。这是一个适用于所有与年龄相关的疾病的问题，它的解决也将推进我们对衰老的基本知识：“为什么老年细胞比年轻细胞更容易受到病理和疾病的影响？“在本世纪的前半叶，人们认为，由于培养的正常细胞是永生的，衰老一定是由细胞外事件引起的。35年前，当我们发现正常细胞的分裂能力确实有限，而且细胞内也会发生年龄变化时，我们推翻了这一教条。我们还观察到，只有异常细胞或癌细胞才是不朽的。正常细胞是致命的，因为端粒在每次分裂时都会缩短，而永生的癌细胞表达阻止端粒缩短的端粒酶。最近，人们发现，当端粒酶基因的催化亚单位被插入正常细胞时，它们变得永生。(C)1998年爱思唯尔科学公司
After performing the miracles that take us from conception to birth, and then to sexual maturation and adulthood, natural selection was unable to favor the development of a more elementary mechanism that would simply maintain those earlier miracles forever. The manifestations of this failure are called aging. Because few feral animals age, evolution could not have favored a genetic program for age changes. Natural selection favors animals that are most likely to become reproductively successful by developing better survival strategies and greater reserve capacity in vital systems to better escape predation, disease, accidents, and environmental extremes. Natural selection diminishes after reproductive success because the species will not benefit from members favored for greater longevity. The level of physiological reserve remaining after reproductive maturity determines longevity and evolves incidental to the selection process that acts on earlier developmental events. Physiological reserve does not renew at the same rate that it incurs losses because molecular disorder increases at a rate greater than the capacity for repair. These are age changes, and they increase vulnerability to predation, accidents, or disease. Failure to distinguish aging from disease has not only blurred our efforts to understand the fundamental biology of aging, but it has profound political and economic consequences that compromise the field of biogerontology. Changes attributable to disease, or pathological change, can be distinguished from age changes for at least four important reasons. Unlike any known disease, (1) age changes occur in every human given sufficient time, (2) age changes cross virtually all species barriers, (3) no disease afflicts all members of a species only after the age of reproductive success, and (4) aging occurs in all feral animals subsequently protected by humans, even when that species probably has not experienced aging for thousands or millions of years. The resolution of age-associated diseases will not advance our knowledge of aging, just as the resolution of the diseases of childhood did not advance our knowledge of childhood development. We have failed to convey that greater support must be given to a question that is rarely posed. It is a question that is applicable to all age-associated diseases, and its resolution will also advance our fundamental knowledge of aging: "Why are old cells more vulnerable to pathology and disease than are young cells?" During the first half of this century it was believed that because cultured normal cells were immortal, aging must be caused by extracellular events. Thirty-five years ago we overthrough this dogma when we found that normal cells do have a limited capacity to divide, and that age changes can occur intracellularly. We also observed that only abnormal or cancer cells are immortal. Normal cells are mortal because telomeres shorten at each division-Immortal cancer cells express the enzyme telomerase that prevents shortening. Recently, it was discovered that when the catalytic subunit of the telomerase gene is inserted into normal cells they become immortal. (C) 1998 Elsevier Science Inc.