How and why we age.

After performing the miracles that takes 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 extra-cellular 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.