Complexity and Interconnection: The Dao, Sade, and Time/Quantum Biology, Part 5
A Short History of Time –
“Time is very slow for those who wait; very fast for those who are scared; very long for those who lament; very short for those who celebrate; but for those who love, time is eternal.” William Shakespeare.
Time is a measure in which events can be ordered from the past through the present into the future, and also the measure of durations of events and the intervals between them. Time is often referred to as the fourth dimension, along with the spatial dimensions.
Sir Isaac Newton had a realist view of time, with events occuring in sequence, as part of the fundamental structure of the universe. Conversely Gottfired Leibniz and Immanuel Kant held that time is neither an event nor a thing, and thus is not itself measurable nor can it be travelled; space and time “do not exist in and of themselves, but … are the product of the way we represent things”, because we can know objects only as they appear to us. Modern physicists generally believe that time is as real as space—though others, such as Julian Barbour in his book The End of Time, argue that quantum equations of the universe take their true form when expressed in the timeless realm containing every possible now or momentary configuration of the universe, called ‘platonia‘ by Barbour.
Until Einstein’s profound reinterpretation of the physical concepts associated with time and space, time was considered to be the same everywhere in the universe, with all observers measuring the same time interval for any event. Non-relativistic classical mechanics is based on this Newtonian idea of time.
Einstein, in his special theory of relativity, postulated the constancy and finiteness of the speed of light for all observers. He showed that this postulate, together with a reasonable definition for what it means for two events to be simultaneous, requires that distances appear compressed and time intervals appear lengthened for events associated with objects in motion relative to an inertial observer.
The theory of special relativity finds a convenient formulation in Minkowski spacetime, a mathematical structure that combines three dimensions of space with a single dimension of time. In this formalism, distances in space can be measured by how long light takes to travel that distance, e.g. a light-year is a measure of distance, and a meter is now defined in terms of how far light travels in a certain amount of time. Two events in Minkowski spacetime are separated by an invariant interval, which can be either space-like, light-like, or time-like. Events that are time-like cannot be simultaneous in any frame of reference, there must be a temporal component (and possibly a spatial one) to their separation. Events that are space-like could be simultaneous in some frame of reference, and there is no frame of reference in which they do not have a spatial separation. People travelling at different velocities between two events measure different spatial and temporal separations between the events, but the invariant interval is constant and independent of velocity.
The brain’s judgment of time is known to be a highly distributed system, including at least the cerebral cortex, cerebellum and basal ganglia as its components. One particular component, the suprachiasmatic nuclei, is responsible for the circadian (or daily) rhythm, while other cell clusters appear capable of shorter-range (ultradian) timekeeping.
Psychoactive drugs can impair the judgment of time. Stimulants can lead both humans and rats to overestimate time intervals, while depressants can have the opposite effect. The level of activity in the brain of neurotransmitters such as norepinephrine and dopamine may be the reason for this. Such chemicals will either excite or inhibit the firing of neurons in the brain, with a greater firing rate allowing the brain to register the occurrence of more events within a given interval (speed up time) and a decreased firing rate reducing the brain’s capacity to distinguish events occurring within a given interval (slow down time).[
Mental chronometry is the use of response time in perceptual-motor tasks to infer the content, duration, and temporal sequencing of cognitive operations.
The Wheel of Time –
Light from the sun sustains life on earth. The 24-h rotation of the earth exposes a vast number of plants and animals to the light/dark cycle. Consequently, the behavior and physiology of numerous living organisms exhibit circadian rhythms. The word “circadian” is derived from Latin circa diem, which means “about a day.” Behavioral rhythms such as sleeping, food seeking, and predator avoidance are thought to help animals survive. Physiological rhythms such as body temperature, blood pressure, and metabolism also anticipate and adapt to predictable changes in the environment to maintain the overall well-being of animals. Circadian rhythms are controlled by evolutionarily conserved internal clocks residing in most tissues of the body. The central clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus and is entrained directly by light. This master pacemaker can synchronize circadian oscillators in peripheral tissues, yet underlying neural and humoral mechanisms remain obscure. Besides light, other external cues such as feeding and ambient temperature are also powerful Zeitgebers (from German for time givers) for peripheral clocks. How these time cues act in concert to entrain tissue-specific oscillators and evoke diverse physiological responses is poorly understood. Nevertheless, these processes clearly involve the endocrine system.
The rhythmic production and circulation of many hormones and metabolites within the endocrine system is instrumental in regulating regular physiological processes such as reproduction, blood pressure, and metabolism. A broad range of metabolites—such as glucose, free fatty acids, cholesterol, and bile acids—also exhibit diurnal fluctuation. A number of these hormones and metabolites serve as ligands for nuclear receptors that direct a large array of transcriptional programs involved in lipid and carbohydrate metabolism. Together, these observations suggest a complex interaction between the circadian clock and nuclear receptor signaling Several recent studies lend further insight into an elaborate “wheel of time” composed of molecular clocks and nuclear receptors, which together help shape an emerging perspective on “design principles” and biological implications of the clock–receptor signaling network.
Peripheral clocks appear to act as the integrators of signals from the light-sensing central clock and other physiological cues. The nature of the signals that entrain peripheral clocks in individual tissues remains obscure. Serving as endocrine and metabolic sensors, a number of nuclear receptors have been implicated in clock entrainment.
Direct protein–protein interactions between clock components and nuclear receptors are emerging as a crucial mechanism for the working of the circadian clock. Virtually all physiological processes—such as growth and differentiation, immune responses, and reproduction—have intrinsic rhythms. The links between the circadian clock and rhythmic cellular and physiological processes are just beginning to be unveiled. A remarkable example is the discovery of the connection between the circadian clock and the cell cycle.
The immune system exhibits distinct diurnal features. Recent studies provide compelling evidence that these diurnal variations are ascribed to intrinsic clockworks in immune cells.
To date, the prevailing view of the circadian system is a hierarchical structure in which the light-sensing master pacemaker and other environmental cues synchronize numerous peripheral oscillators via the “input” pathways and, subsequently, drive rhythmic physiologic “outputs.” Much effort is focused on the identification of molecular components of the input and output pathways. However, as exemplified by the interactions between the circadian clock and nuclear receptors, feedback loops are pervasively present at the molecular, cellular, tissue, and systems levels. The boundary between the input and output pathways is dissolving. Thus, it is probably time to revisit the role of the circadian system in whole-body physiology. In addition to keeping internal physiology synchronized with the environment—predominantly the light/dark cycle—circadian clocks may serve at least two other ancient purposes: (1) to temporally separate chemically incompatible metabolic processes, such as anabolism and catabolism; and (2) to coordinate distinct physiological processes to maintain dynamic homeostasis. Evidence for these scenarios is emerging.
As illustrated in figure below, it seems that connections between the circadian clock and most (if not all) physiological processes are bidirectional. Therefore, the circadian system might provide a potential means of communications between different physiological domains. In view of the dissolving boundary between different physiological processes, the circadian clock is probably not merely a timekeeper, but also a guardian of physiological homeostasis.
To be continued.
Georges M. Halpern, MD, PhD