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Biological Aging Is No Longer an Unsolved Problem



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Biological Aging Is No Longer an Unsolved Problem LEONARD HAYFLICK Department of Anatomy University of California San Francisco School of Medicine The Sea Ranch California 95497 USA ABSTRACT The belief that aging is still an unsolved problem in biology is no longer true Of the two major classes of theories the one class that is tenable is derivative of a single common denominator that results in only one fundamental theory of aging In order to address this complex subject it is necessary to first define the four phenomena that characterize the finitude of life These phenomena are aging the determinants of longevity age associated diseases and death There are only two fundamental ways in which age changes can occur Aging occurs either as the result of a purposeful program driven by genes or by events that are not guided by a program but are stochastic or random accidental events The weight of evidence indicates that genes do not drive the aging process but the general loss of molecular fidelity does Potential longevity is determined by the energetics of all molecules present at and after the time of reproductive maturation Thus every molecule including those that compose the machinery involved in turnover replacement and repair becomes the substrate that experiences the thermodynamic instability characteristic of the aging process However the determinants of the fidelity of all molecules produced before and after reproductive maturity are the determinants of longevity This process is governed by the genome Aging does not happen in a vacuum Aging must be the result of changes that occur in molecules that have existed at one time with no age changes It is the state of these pre existing molecules that governs longevity determination The distinction between the aging process and age associated disease is not only based on the molecular definition of aging described above but it is also rooted in several practical observations Unlike any disease age changes a occur in



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