The role of time in metabolism can be viewed in a much broader context than is typically discussed. Scales of time in the universe are interlinked with scales of space. Organization of matter in the universe is hierarchical which means that subatomic structures of elementary particles occupy dimensions below a femtometer (10-15 m) and are engaged in processes occurring on a time scale shorter than a femtosecond (10-15 s). The part of physics with relevance to chemistry and hence to biology begins here. Atomic dimensions span a range from an angstrom (10-10 m), which is roughly the size of a hydrogen atom, all the way to the macromolecular dimensions. Correspondingly, atomic bond vibrations are cyclical processes that take place on the time scale of a picosecond (10-12 s). The world of biomolecules, biomolecular ensembles, their superstructures and higher organizational compositions including organisms covers an enormous swath of sizes between nanometers (10-9 m) which correspond to protein dimensions to meters corresponding to the dimensions of large organisms with cellular dimension in the range of tens of micrometers. The spread of time scales in biological processes is even larger and it begins at the nanosecond (10-9 s) range for rapid conformational changes, through microseconds (10-6 s) for cellular diffusion processes, to milliseconds (10-3 s) for ion channel opening/closing events to hours (10 3 -10 4 s) for cell division to tens of years for life spans of organisms (10 9 s). Beyond these scales we enter into geological scales of transformations of our planet taking millions of years and thousands of kilometers. The ultimate scale of spatio-temporal organization of matter is that of the Universe itself, which is believed to be 14 billion years old and its size is estimated to be 93 billion light years in diameter, which is an unimaginably large number.
This discussion is not only intended to give a humbling perspective on the comparisons of scales of time and space relative to our own physiological scale but also a realization that the Universe operates on the principle of cycles within cycles. We have made a strong emphasis on this idea when discussing our own metabolic cycles and the molecular clocks. Our lives revolve around the cycles of metabolic energy production (1 ms per ATP molecule production), which then combine multiple times to give rise into diurnal cycles governed by the light/dark cycles. Additionally, we are also susceptible to lunar (monthly) cycles and solar cycles of seasons of the year. This is also important in view of aging which is due to the emergence of the arrow of time resulting from entropy production when perfect periodicity of cyclical reactions becomes compromised due to the wear and tear of the machinery of all living cells. Perfectly cyclical processes, including chemical reactions, do not produce entropy by virtue of being reversible. Only when a process becomes irreversible, does entropy increase between the initial and final states and hence an arrow of time emerges. As we age, this becomes more and more pronounced and many of us unleash a losing battle trying to erase the visible signs of aging. Instead, as we amply advocated in the many sections of Vol. 2 of this book, a better approach is to continuously optimize our state of health. We do this by respecting the physiological cycles of sleep/wakefulness, fasting/feeding and other circadian behaviors, adhering to a qualitatively and quantitatively healthy diet, being meaningfully connected to our social network of family, friends and communities, as well as encouraging vitalizing stressors and minimizing toxic stress.
It’s intriguing that this message links physiology once again to physics through some of the most unexpected metaphors. Special Theory of Relativity teaches us about the possibility of time dilation when we move at a high velocity with respect to the reference frame. This means that time is related to the speed of moving through space compared to a stationary frame of reference. In the limit of attaining the speed of light, time stands still. Hence, we can imagine this as metaphorically akin to the relative measure of human lifespan depending on the rates at which internal molecular clocks operate compared to the person’s chronological age. In this vein, when proper synchronization occurs across the human body, these molecular clocks slow down and operate in perfect synchrony leading to a maximum lifespan possible, say 120 years. On the other hand, when they speed up due to the metabolic demands that require faster operations or when they become decoupled from each other as a result of disease states, the lifespan (and the healthspan) is shortened. Time dilation in the case of perfect health corresponds to the slowing down of molecular clocks as a function of scale. Time scales are hierarchically linked to spatial dimensions. Fast processes take place on molecular levels while slow processes, due to intricate coupling of many networks, occur on macroscopic levels of organs, tissues and organisms. Decoupling leads to desynchronization resulting in a speed-up of local processes. This is evident through allometric laws of physiology discussed in connection with quantum metabolism in Vol. 1 of this book. Quantum biological processes transcend the classical aging process, and slow it down while classical metabolism speeds it up by excessive entropy production leading to biological aging which produces an accelerated diversion from chronological time. For example, an individual whose chronological age is 60, within a one year period of experiencing chronic stressors or clinical illness, may incur accelerated biological aging of 10 years such that at the chronological age of 61, the new biological age is 71 years. In this case, the allometric scaling laws come into play whereby the beta exponent of 3/4 in the quantum metabolic regime changes to isometry (exponent of 1) in classical metabolism increasing the metabolic rate and speeding up aging. However, this is another interesting parallel between relativistic physics and physiology. Namely, time dilation occurs also in General Theory of Relativity when an object moves close to a large mass, which “bends” the spatio-temporal continuum. Correspondingly, we can say that we can effectively increase our lifespan by being within the range of attraction of larger masses, which can be understood here as our network of family and friends. This effect helps us reduce the stress we live under by spreading the “toxic load” among our social support system.
An anecdote about one of the greatest cosmologists of all time, Stephen Hawking, speaks directly to the important role of the deep human connections to other humans in maintaining our health and extending the lifespan, sometimes even against all odds. When Hawking was diagnosed with ALS at the age of 22, he told his fiancée that: “The Universe would have no meaning if it were not the home of people you love”. He was given only 2 years to live by his doctors, which is indeed typical for this stage of the disease. At that time he was only 2 years into his PhD, which he completed two years later at 24, then went on to marry, have 3 children and hold the Lucassian Professorship in Mathematics at the University of Cambridge, the most prestigious academic position in the world established in 1663 that had been held in the past by none other than Sir Isaac Newton. Hawking contributed more to the physical sciences than anyone since Einstein, creating legacies along the way that gave him the will and the purpose that with the support of others helped him survive for 54 years following this dreadful diagnosis! He played an iconic role in science, both high-brow and popular, by attracting the fascination of fellow researchers in the field of modern cosmology as well as generating public interest in science and in scientists. Writing popular books and giving public lectures and interviews may have equaled or even exceeded his personal contributions to scientific literature. In connection with the Physiological Fitness Landscape, examples like this may pose an important challenge to incorporate in its quantitative algorithms such aspects as the meaningful life, a life lived with a purpose, grit and determination as well as the support network of family, friends and professional colleagues. This invokes the notion of physiological purpose, and the significance of networks of support systems that promote survival of life forms at all scales.
One of the closest collaborators of Hawking’s was Sir Roger Penrose. In a recently published breath-taking prediction, this 2020 Nobel Prize winning physicist, and another cosmologist of greatest caliber, proposed the idea of a cyclical Universe, which oscillates between a Big Bang and a contraction to a massive black hole, followed by another Big Bang, etc. forever into the future. These cyclical universes are envisaged to be all born at the moment of a Big Bang and die with a black hole collapse of all matter and light into a singularity point. The period of these enormously long oscillations has been named an aeon. If true, the superposition of both cyclic and entropic processes that manifest our human physiology as we have stressed repeatedly in this book is a metaphor for the entire Universe where the emergence of a first black hole in the tapestry of galactic matter signals a gradual descent into a cosmic period of aging culminating with a total collapse. I can’t help but marvel at how beautifully poetic and optimistic is Penrose’s promise of a rebirth of the Universe following its collapse into a singularity point.