A Core Molecular Theory of Sleep and Aging

Lemont      B. Kier

Abstract

Models of water in the presence of amino acid side chains have revealed significant variability in the local water structure, reflecting the variations in the hydropathic states of the side chains. These models also reveal patterns of water cavities, termed chreodes, that may exist near the surface of a protein. These patterns have been invoked to explain the facilitated diffusion of ligands to an active site on the protein surface. The action of a volatile, general anesthetic agent has been proposed to occur from the interruption of these chreodes producing some loss of function from the receptor. The many similarities reported between the effects of a general anesthetic agent and sleep have produced a proposal of a common mechanism. In the case of sleep, it has been proposed that inhaled elemental nitrogen accumulates to produce a mild anesthesia. Sleep is the process of reversal of this accumulation. It is proposed that over a lifetime there is a continued accumulation of nitrogen with accompanying influences on many processes, leading to a gradual decline of many functions, called aging. The sequence of these concepts is reviewed here.

Keywords: Aging, sleep, water chreodes, cellular automata, elemental nitrogen, QSAR, molecular modeling, molecular dynamics, chaperones, Monte Carlo simulations