Hayflick L
Department of Anatomy, University of California, San Francisco, School of Medicine, Sea Ranch, USA.
Keio J Med. 1998 Sep;47(3):174-82. doi: 10.2302/kjm.47.174.
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 discovered that normal cells do have a limited capacity to divide and that aging occurs intracellularly. We also observed that only 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 the telomerase gene when inserted into normal cells immortalizes them. There appears to be a relationship between these findings and aging, longevity determination and cancer. 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. This failure is called aging. Because few feral animals age, evolution could not have favored animals exhibiting age changes. Natural selection favors animals that are most likely to become reproductively successful by developing greater survival skills and reserve capacity in vital systems to better survive predation, disease, accidents and environmental extremes. Natural selection diminishes after sexual maturation because the species will not benefit from members favored for greater development of physiological reserve. A species betters its chances of survival by investing its resources and energy in increasing opportunities for reproductive success rather than on post-reproductive longevity. The level of physiological reserve remaining after reproductive maturity determines potential 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. These age changes increase vulnerability to predation, accidents or disease.
在本世纪上半叶，人们认为由于培养的正常细胞是永生的，衰老必定是由细胞外事件引起的。35年前，我们推翻了这一教条，当时我们发现正常细胞确实具有有限的分裂能力，而且衰老发生在细胞内。我们还观察到只有癌细胞是永生的。正常细胞会死亡是因为端粒在每次分裂时都会缩短。永生的癌细胞表达能防止端粒缩短的端粒酶。最近，人们发现将端粒酶基因插入正常细胞会使其永生。这些发现与衰老、寿命决定和癌症之间似乎存在某种关系。在完成了从受孕到出生，再到性成熟和成年的奇迹之后，自然选择无法促使一种更基本的机制发展，这种机制本可简单地让那些早期奇迹永远持续下去。这种失败就被称为衰老。由于很少有野生动物会衰老，进化不可能青睐表现出衰老变化的动物。自然选择青睐那些最有可能通过发展更强的生存技能以及重要系统中的储备能力来在捕食、疾病、事故和极端环境中更好地生存从而实现繁殖成功的动物。性成熟后自然选择的作用就会减弱，因为物种不会从那些因生理储备得到更大发展而受到青睐的个体中受益。一个物种通过将资源和能量投入到增加繁殖成功的机会而非繁殖后的长寿上，来提高其生存几率。生殖成熟后剩余的生理储备水平决定了潜在寿命，并且是在作用于早期发育事件的选择过程中附带进化而来的。由于分子无序性增加，生理储备的更新速度跟不上其损耗速度。这些衰老变化增加了遭受捕食、事故或疾病的脆弱性。
