A brief history of the mortality and immortality of cultured cells

Abstract

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.