THE NATURE OF SLEEP, DREAMS, AND AGING: A THEORY INVOLVING CONFORMATIONAL CHANGES OF BIOPOLYMERS WALTERJ. KLEINSCHMIDT* A theory is the more impressive the greater is the simplicity of its premises, the more different are the kinds ofthings it relates and the more extended ¿s its range ofapplicability. [Albert Einstein] Why do we sleep, dream while we sleep, and why do we grow old? These questions occur to everyone and have been asked throughout the ages. Often we would like to do without sleep or at least postpone it, and Certainly most of us would happily relinquish the experience of aging. We seem to have some understanding of these questions of sleep, dreams, and aging. Certainly our language indicates that we do. We sleep because we are tired and we are refreshed after a night's sleep, and so we speak of sleep as essential for recovery from stress and fatigue. Many a child has had "explained" to him why he must go to bed, the necessity of sleep for health and well-being, that during sleep our "batteries" are recharged, and our energies recouped to meet the demands of another day. His fears from a "bad" dream are assuaged by reassuring him that dreams are a normal occurrence during sleep, again apparently essential for health; that everyone experiences them; and that sometimes they take peculiar forms. Agingis "explained" by comparingour body to a machine and speaking of it as wearing down or out. The functions and processes of these important physiological phenomenaofsleep, dreams, and agingare so commonplace that they are taken for granted and therefore largely thought to be understood. Critical scrutiny tells us, however, that they are little understood and, indeed, these important physiological functions ofour lives remain as deep mysteries . Though recent research may have determined (we should perhaps say affirmed) that sleep and dreams are needed for health, we still do not have an answer as to reasons for this need. The biochemist searches for a mechanistic answer and his interest converges to the molecular level. He asks, "What body constituents, what molecules, are involved?" ?The Lilly Research Laboratories, Indianapolis, Indiana 46206. Perspectives in Biology and Medicine · Spring 1974 | 371 The basic biochemical constituents of the animal organism include the following components: nucleic acids, proteins, lipids, and polysaccharides . These, ofcourse, occur as separate entities, but they also exist in conjugated form as nucleoproteins, lipoproteins, glycoproteins, phosphoproteins , scleroproteins, metalloproteins, chromoproteins, lipopolysaccharides, etc. Significantly the prefix "proteo-" is seldom used in describing these complexes. Proteins are essential to all protoplasm. Functionally and structurally, they are characteristic of living matter, and therefore seem to hold the position of greatest importance. Nucleic acids may be essential for directing their synthesis, but once formed, the proteins exert a dominance. Structurally, the body organism is composed ofcells, which themselves contain or compose membranes, filaments, fibers, fibrils, gels, sacs, sheaths, etc, all distinguished by their protein content. In aggregate, these entities make up what we call tissues. Recent research has revealed that conformational changes readily take place in biopolymers and that biological activity is greatly influenced by these conformational changes. Anfinson recently was awarded the Nobel Prize for his investigations on ribonuclease. He observed that the ribonuclease molecule whose sulfide bridges had been reduced to free sulfhydryl groups slowly regained its activity in air via reoxidation of the disulfide. He astutely ascribed this regaining ofactivity to a conformational alteration back to its original form [I]. Nomura and his co-workers [2] and Senior and Holland [3] have very recently determined that the mechanism of the killing action of the bacteriocins of Escherichia coli involves a conformational change of a protein. The attachment of the bacteriocin to the bacterial cell triggers a protein within the cell membrane to undergo a change in conformation. This alteration in configuration imparts to the protein an enzymatic activity, that of a ribonuclease. This activated ribonuclease now has the capacity to hydrolyze the ribosomal RNA into two separate parts precluding further protein synthesis, a lethal result to the cell. Conformational changes can be produced on proteins by means of certain drugs. Effective antiinflammatory drugs, for example, displace bound tryptophan from serum albumin. Sjöholm and Grahnen [4], by circular dichroism...