Biological Aging Is No Longer an Unsolved Problem

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 re- sults 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 deter- minants of longevity, age-associated diseases, and death. There are only two fundamental ways in which age changes can occur. Aging occurs ei- ther 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, acci- dental events. The weight of evidence indicates that genes do not drive the aging process but the general loss of molecular fidelity does. Poten- tial 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, re- placement, and repair, becomes the substrate that experiences the ther- modynamic 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 every multicellular animal that reaches a fixed size at reproductive maturity, (b) cross virtually all species barriers, (c) occur in all members of a species only after the age of reproductive maturation, (d) occur in all animals removed from the wild and protected by humans even when that species probably has not experienced aging for thousands or even mil- lions of years, (e) occur in virtually all animate and inanimate matter, and (f ) have the same universal molecular etiology, that is, thermodynamic instability. Unlike aging, there is no disease or pathology that shares these six qualities. Because this critical distinction is poorly understood, there