Biological Clock | Zoology Optional Notes for UPSC PDF Download

Life evolved with the 24-h rotation of the Earth

As a result, organisms have evolved ways to measure daily time intrinsically with circadian clocks, which allow for anticipation of events. Many changes to physical, mental, and behavioral state are governed by endogenous circadian clocks. As a result, disruptions of clocks, which can because by misalignment between the environment and internal clocks or dys-synchrony of clocks within an organism, can have pathologic consequences. We review here the impact of clocks on overall physiology and the relevance of circadian disruption to disease, with a focus on metabolic and neurologic disorders.

Clinical Implications of Biological Clocks

From the endocrinology and clinical medicine standpoints, the daily rhythms have long been known to be manifested in organismal physiology, compared to other fields of systems biology. The discovery of the mammalian and fly circadian genes unveiled genetic mechanisms behind temporal processes. There is a crosswalk between metabolism and biological clock, and these are intertwined at the level of basic property of homeostatic equilibrium in the body. Biological clocks have clinical implications, and the understanding of how bodies work at a molecular level is recent information revealed through functional genetic approaches. Studies on model species like cyanobacteria, drosophila, mice, etc. have contributed to the knowledge of human circadian rhythms, for example, how feeding or other behavioral rhythms are associated at the level of temporal organization. Just as Clock mutant mice, which had disorganized circadian sleep/wake behavior, also gained weight if they were challenged with a high-fat diet. This finding suggested that the clock system and the related sleep/wake cycles it regulates might somehow intersect with the behavioral circuitry that controls weight homeostasis.

Chronobiology and Diseases

While the concept of nutrient homeostasis sits at the basis of knowledge that nutrient systems control weight and that abnormalities in weight or obesity are due to an abnormality in these long-term homeostatic or short-term satiety systems. Chronobiologists started to think that sleep/wake behavior and photoperiodism could be regulating fundamental nutrient-responsive homeostatic systems. As they sought to genes that control behavior related to feeding, molecular studies in terms of endocrine physiology viz. pathways controlling body weight, and transcription factors underlying the regulation of β-cell function became important. Nowadays, the use of approaches from next-generation sequencing has enabled testing how clocks exert these diverse control processes.

Insulin Secretion and Function

This unit is specifically from the focused work of Joseph Bass at Northwest University, USA, who utilized his knowledge of the biology behind insulin production, and the genes that regulate physiology and biochemistry. The idea was that its clock genes that encoded transcription factors must be involved in regulating insulin production in the pancreatic β-cells. He has proven that the clock system in the pancreas controls insulin secretion. The link between clocks and pancreatic β-cell function unveiled the mystery behind fundamental regulatory control of β-cells.

Drosophila, Mice Mutants, and Human Clock Studies

Benzer and Ron Konopka, working on Drosophila genetics showed that genes control behaviors, including genes that control sleep/wake behavior and encode transcription factors that operate through a feedback mechanism in the brain. The clock genes are widely expressed in every organism and present in nearly every cell throughout the body. Genetic studies in mice started with mouse clock system genes. Almost all aspects of human life are now well investigated in mice through genetic mice using techniques like knock out, etc. Clinical and research studies have suggested a link between Parkinson’s disease (PD) and alterations in the circadian clock. Drosophila melanogaster may represent a useful model to study the relationship between the circadian clock and PD. Apart from the conservation of many genes, cellular mechanisms, signaling pathways, and neuronal processes, Drosophila shows an organized central nervous system and well-characterized complex behavioral phenotypes. In fact, Drosophila has been successfully used in the dissection of the circadian system and as a model for neurodegenerative disorders, including PD.

Circadian Rhythm Abnormalities in Parkinson’s Disease

Studies indicate a role for the circadian system in the oxidative stress pathways in the heart and brain after MI. This fusion of circadian biology with cardiac oxidative stress pathways is novel and offers enormous potential for improving our understanding and treatment of heart disease. At an epidemiological and clinical level, metabolic and endocrine systems are among the most overt in terms of the connection to a timing mechanism because glucose is metabolized differently in the day and night. Liver metabolism also varies during the day and night across many different pathways, including the detoxification pathways, the generation of sterols and other macromolecules, and the activation of mitochondria and the production of energy. All these processes are alternating by day and night, and this is controlled by the circadian clock. Shift workers are more susceptible to diabetes and there is also a correlation with body weight and sleep time—thus, there is a rationale for focusing on the endocrine system.

Need for Chronomedicine

Now that there is enough applied chronobiology information and intellectual revolution, it hasn't yet translated into a therapeutic change because it’s pleiotropic, affects many different processes, and it’s a matter of working through where the system can be manipulated in such a way as to improve health in a certain disease. Another important area to mention is cell growth, immune signaling, and inflammation. These are all processes in which there are intersections with the clock, and even the basics of what we know about aging are interlinked with clock processes. Many different systems are affected; this is a conceptual entry point into a broad range of opportunities for understanding disease.

How Mechanism Behind These Diseases are Studied

Scientists try to detect hormonal deficiency by challenging the axis required for a hormone to elicit an effect. Franz Halberg (1919–2013) developed chronobiology and founded the field of chronomedicine including chronomics, chronoastrobiology, and chronobioethics. He coined the term circadian, after documenting that biologic rhythms tip the scale between health and disease and even between life and death. He showed that the large extent of cardiovascular variations can be exploited in the form of dynamic and other endpoints derived for each individual, for use in preventive as well as curative health care.

Main Applications of Chronobiology

The main applications of chronobiology are in preventative medicine, diagnostics, and molecular tools to intervene in metabolic and other systems. An example is a hospital setting where continuous tube feedings to critical care patients are in conflict with the endogenous circadian program and that this exacerbates insulin resistance in response to tube feedings. There are intensive care units where drug or nutrient infusions are provided without consideration for the clock, leading to the disorganization of the circadian alignment of different systems. This is an area that needs to be carefully considered in clinical medicine because we are potentially exacerbating problems. Chronopharmacology describes how certain drugs are metabolized differently at different times of the day and, therefore, it may be optimal when studying drug metabolism to test the levels of the drug at different times in the cycle and to take advantage of this information to adjust and manipulate drug dosing.

Impact of Circadian Clock Research on Understanding of Diseases

Chemical approaches that identify, in an unbiased way, molecules that may restore the system to the setting in the event of an altered clock. As our understanding of how the clock controls basic processes will continue to evolve, as well as genome biology and its downstream effectors. We really don’t know the connectivity from the clock to all the other systems that it controls or what these connections are or how they respond under perturbed conditions. In the brain, we have very sophisticated tools to question how brain centers control all sorts of functions and to elucidate exactly the interactions of the clock systems with other pathways. It is a very rich interdisciplinary field, there are many talented investigators, and there are several angles that will provide exciting new insights in both the fly and the mouse systems. It will also provide insights into sleep, which is an area where we really don’t understand much about the molecular underpinnings but which will be hugely important to reveal.