Chronomics and chronobiology in health and disease (original) (raw)
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Chronomics and “Glocal” (Combined Global and Local) Assessment of Human Life
Progress of Theoretical Physics Supplement, 2008
Most organisms, from cyanobacteria to mammals, are known to use circadian mechanisms to coordinate their activities with the natural 24-hour light/dark cycle and/or interacting socio-ecologic schedules. When the human clock gene was discovered in 1997, it was surprising to see that it was very similar in all earthly life. Recent findings suggest that organisms which evolved on Earth acquired many of the visible and invisible cycles of their habitat and/or of their cosmos. While circadian systems are well documented both time-macroscopically and timemicroscopically, the temporal organization of physiological function is much more extensive. Long-term physiological quasi-ambulatory monitoring of blood pressure and heart rate, among other variables, such as those of the ECG and other tools of the neuroendocrinologic armamentarium, have already yielded information, among others, on circaseptan (about 7-day), transyears and cisyears (with periods slightly longer or shorter than one year, respectively), and circadecennian (about 10-year) cycles; the nervous system displays rhythms, chaos and trends, mapped as chronomes. Chronomes are time structures consisting of multifrequency rhythms covering frequencies over 18 orders of magnitude, elements of chaos, trends in chaotic and rhythmic endpoints, and other, as-yet unresolved variability. These resolvable time structures, chronomes, in us have counterparts around us, also consisting of rhythms, trends and chaos, as is increasingly being recognized. In 2000, we began a community-based study, relying on 7-day/24-hour monitoring of blood pressure as a public service. Our goal was the prevention of stroke and myocardial infarction and of the decline in cognitive function of the elderly in a community. Chronomic detection of elevated illness-risks aim at the prevention of diseases of individuals, such as myocardial infarctions and strokes, and, equally important, chronomics resolves illness of societies, such as crime and war, all exhibiting some already mapped cycles, that are indispensable for the study of underlying mechanisms. A variety of cognitive, neurobehavioral and neuropsychological as well as cardiovascular functions will need to be investigated to more precisely map their chronomes in space and time, in order to understand chronoastrobiology, based on both the system times and time horizons yielded by chronomes assessed in communities worldwide. Thus, we critically introduce a preventive health care, while keeping the flow of data for the assessment of space weather and its consequences in the evolution thus far of terrestrial life.
Chronobiology's progress. Part II, chronomics for an immediately applicable biomedicine
J. Appl. Biomed, 2006
Chronomic cardiovascular surveillance serves to recognise and treat any risk elevation as well as overt disease, and to ascertain whether treatment is effective and, if so, for how long treatment effects lasts, be it for lowering an increased risk and/or in surveilling the success or failure of treatment. A treatment-associated increase in circadian amplitude of blood pressure (BP) may induce iatrogenic overswinging, also dubbed CHAT (circadian hyper-amplitude-tension), in some patients, thereby increasing cardiovascular disease risk unknowingly to care provider and receiver.
Journal of Applied Biomedicine, 2006
New components of transdisciplinary spectra or known components in new variables in us, matching those around us, are being mapped. Their hardly trivial interactions associated with the good and bad around us-from religiosity to crime and war-are being rendered measurable, for the eventual development of countermeasures to the diseases of societies and nations. Internal cycles not only underlie life itself and underlie our evolving genetics at all levels of organization; they also constitute the essential control and reference information in all transdisciplinary science. In preparing for travel to Mars and other missions in space that may take more than a year, let us do what is immediately practicable. Transyears may have very small amplitudes yet are associated with sudden cardiac death in some terrestrial locations; if they should play a role in these electrical incidents of the heart, among others like myocardial infarction and stroke, they will jeopardize lengthy missions in extraterrestrial space, away from hospitals. The likelihood of stroke or cardiac death can be immediately reduced by chronobiologically assessing blood pressure and heart rate variability and by optimizing the efficacy of timed treatment rather than relying on an unacceptable and often inaccurate spotcheck and treating by convenience rather than pertinence. Needed are: detection of nocturnal abnormality when medication may no longer be effective (or is too effective) neither seen during office visits by day; detection of circadian hyperamplitude-tension (CHAT) associated with a risk of stroke and kidney disease greater than other risks Halberg et al.: Chronobiology's progress I 2 (including "hypertension" when all risks are assessed concomitantly); detection of CHAT as high risk among normotensives who may not need anti-hypertensive medication; individualized inferential statistical testing to determine whether a drug or non-drug intervention such as autogenic training (relaxation) is effective and for how long (detecting any initial and later success or failure), some of which conditions otherwise are not found without chronobiology; individualization of treatment timing, since the same dose of the same medication can further lower the subject's blood pressure average and circadian amplitude when the timing of daily administration is optimized, as ascertained by sequential testing and parameter tests. Thus, we save lives by monitoring and assessing, and if need be treating, vascular disease risk through chronobiologically interpreted 24-hour or preferably longer (24-hour/7-day) blood pressure and heart rate variability. Abnormalities in the variability of blood pressure and heart rate, impossible to find during a conventional office visit (the latter aiming at the fiction of a "true" blood pressure), can raise cardiovascular disease risk in the next six years from 4% to 100%. Keywords: chronobioethicsgliding spectrablood pressureheart ratetravel to Mars • Dedicated to Alejandro Zaffaroni, who came as a pleasant surprise with flowers and more. May a marker-guided preventive chronotherapy of elevations of the risks of diseases not only of individuals but also of societies and nations eventually evolve.
Essays on chronomics spawned by transdisciplinary chronobiology. Witness in time: Earl Elmer Bakken
Neuro endocrinology letters, 2001
Technology allows the monitoring of ever denser and longer serial biological and physical environmental data. This in turn allows the recognition of time structures, chronomes, including, with an ever broader spectrum of rhythms, also deterministic and other chaos and trends. Chronomics 1 thus resolves the otherwise impenetrable "normal range" of physiological variation and leads to new, dynamic maps of normalcy and health in all fi elds of human endeavor, including, with health care, physics, chemistry, biology, and even sociology and economics. The authors plan to describe initiators of modern mapping of our make-up in time, with focus on mechanisms and applications. Earl Elmer Bakken, to start the planned series, is also to serve as a local time-witness (Zeit-Zeuge) of concerns about chronomics in Minnesota.
Chronomics for chronoastrobiology with immediate spin-offs for life quality and longevity
Biomedicine & Pharmacotherapy, 2003
Effects of geomagnetic disturbance on heart rate variability (HRV), the 1/f fractal scaling in particular, are being assessed in adults living at high latitude, where magnetic storms are more frequent and more intense than at lower latitudes. The latter may constitute a signal or a proxy, and possibly a mechanism underlying both undesirable and desirable effects, depending upon circumstances yet to be elucidated. Any circadecadal stage-dependence of morbidity and/or mortality from certain conditions such as myocardial infarctions remains to be studied in both adult and pediatric populations. Further work could thus examine whether any associations of geomagnetic disturbances may account, at least in part, through effects upon the circulation, for long-term infra-annual changes, possibly anchored in the population's gene pool, observed in a number of anthropologic measurements at birth as well as in other population statistics. In order to assess the development of several chronome components of the electrocardiogram (ECG), around-the-clock ambulatory ECG were recorded from 19 infants (25 days-3 months of age), 22 children (3-9 years of age), 18 boys and girls (10-14 years of age), pubertal boys (15-20 years of age), and 10 young men (21-29 years of age). Time-and frequency-domain measures of HRV were obtained by spectral analysis, using the maximal entropy method (MEM). The frequency of detection of the circadian, circasemidian and circaoctohoran components, with periods of about 24, 12 and 8 h, respectively, was compared among the five groups for several HRV endpoints, notably 1/f fractal scaling, total spectral power within a 5-min span, and its distribution into several frequency regions. A circadian component is already detectable in a sizeable proportion of infants and children for most of the HRV indices considered. The incidence of detection of the circadian component increases with age for the spectral power in different frequency regions, notably around 10.5 s ("LF") and around 3.6 s ("HF"); it peaks around puberty for 1/f in our data; and it did not detectably change with age for the total spectral power. Similar changes with age are not observed for the circasemidian or circaoctohoran components. The latter characterizes primarily 1/f and less so the about 3.6 s power ("HF"). Several aspects of the HRV chronome may thus develop differently as a function of age. In 2000, we began a community-based study named "Longitudinal Investigation of Longevity and Aging in Hokkaido County (LILAC study)". The ambulatory blood pressure (BP) of middle-aged subjects, aged 40-74 years, was monitored 7-day/24-h, and the cardiovascular and neurobehavioral functions of elderly people above 75 years were evaluated. Our goal was the prevention of stroke and myocardial infarction and the decline in cognitive function of the elderly in a community. Of 115 elderly people recruited in a longitudinal community-based study in 2000, 72 completed yearly follow-ups in 2002. A cardiovascular score based on BP, pulse wave velocity, and 1-h ECG-based HRV endpoints served to distinguish between normal, mildly disordered, or disordered participants. A comparison of cognitive function in 2002 vs. 2000, assessed with the MMSE, HDSR, the Up & Go and Functional Reach tests, gauged any effect of social intervention. Cognitive function was maintained or improved, especially for people suffering from hypertension, tachycardia, or a decreased HRV, suggesting that cardiovascular function is a major factor affecting cognitive function.
Chronobiology and chronomics: detecting and applying the cycles of nature
Biologist (London, England), 2009
We monitor our streets to prevent assault and rodents to develop drugs, but not those for whom the drugs are intended. It took over half a century to begin to monitor blood sugar values in patients with insulin-dependent diabetes. Monitoring blood pressure is equally timely and technically feasible for individual home- and website-based personalised care. It also serves basic science and someday perhaps the management of societal illnesses.
Annals of the New York Academy of Sciences, 2006
A BSTRACT : The spectrum of biological rhythms is extended far beyond circadians, circannuals, and ultradians, such as 1.5-hourly melatonin and 8-hourly endothelin-1 (ET-1) rhythms by statistics of natality, growth, morbidity, and mortality, some covering decades or centuries on millions of individuals. These reveal infradian cycles to be aligned with half-weekly rhythms in ET-1, weekly and half-yearly ones in melatonin, and even longer-about 50-, about 20-, and about 10-year cycles found in birth statistics. About daily, weekly, yearly, and ten-yearly patterns are also found in mortality from myocardial infarctions; the 10-yearly ones are also in heart rate and its variability; in steroid excretion, an aspect of resistance, for example, to bacteria; and in the genetic changes of the bacteria themselves. Automatic physiological measurements cover years and, in one case, cover a decade; the latter reveal an about 10-year (circadecennial) cycle. ECGs, covering months beat-to-beat, reveal circaseptans, gaining prominence in response to magnetic storms or after coronary artery bypass grafting. A spectrum including cycles from fractions of 1 Hz to circasemicentennians is just one element in biological time structures, chronomes. Chaos, trends, and any unresolved variability are the second to fourth elements of chronomes. Intermodulations, feedsidewards, account for rhythmically and thus predictably recurring quantitative differences and even for opposite treatment effects of the same total dose(s) of (1) immunomodulators inhibiting or stimulating DNA labeling of bone in health or speeding up versus slowing down a malignant growth and thus shortening or lengthening survival time, or
Journal of Experimental Therapeutics and Oncology, 2003
y Chronomics: imaging in time (Insert 1). Physiologic variability, a formidable enemy when ignored, can be made into a powerful source of new information with clinical applications. This is the task of the science of chronobiology, which developed originally from genetics. Mendelian genetics started with plant hybridization, whereas in Minnesota, as a new science on an old topic, chronobiology began as a spin-off of genetics with studies on inbred mice by 1950. Genetics eventually led to genomics, the mapping of genes and the cloning of organisms. Concurrently, the study of biological variability led to circadian rhythms, then to chronobiology, and thus to the mapping of ever broader time structures, the chronomes (from chronos ¼ time and nomos ¼ rule). Chronomics maps computer-analyzed elements of variability in and around us. Chronomes can include, in dense series, numerically assessed endpoints of 1) deterministic chaos that undergoes, 2) rhythms, the major predictable element and, notably in long series, also 3) trends that, as the series become long enough, eventually can turn out to be rhythms with ever longer periods, up to one or several decades in individuals and still longer periodicities in populations. It does not suffice to focus, e.g. on the frequency of a cardiac cycle, upon the 'low frequency' of current concerns about heart rate variability (HRV), when circadecadals may modulate rhythms with shorter periods, as they may well do with a biological day, week, half a year, and/or $1.3-year. DIVERSITY IN SPACE: GENETICS VARIABILITY IN TIME: CHRONOBIOLOGY MAPPING GENOMICS CHRONOMICS CHRONOMICS, the mapping of time structures, i.e., of chronomes (from chronos, time, and nomos, rule), of each pertinent variable, in us and around us, near and far, with cycles eventually coded in genomes by an adaptive evolution, others still resonating in us by mechanisms evolved as an integrative evolution Insert 1: Complementarity in biological diversities
Scripta medica
The mapping of time structures, chronomes, constitutes an endeavor spawned by chronobiology: chronomics. This cartography in time shows signatures on the surface of the earth, cycles, also accumulating in life on the earth's surface. We append a glossary of these and other cycles, the names being coined in the light of approximate cycle length. These findings are transdisciplinary, in view of their broad representation and critical importance in the biosphere. Suggestions of mechanisms are derived from an analytical statistical documentation of characteristics with superposed epochs and superposed cycles and other "remove-and-replace" approaches. These approaches use the spontaneously changing presence or absence of an environmental, cyclic or other factor for the study of any corresponding changes in the biosphere. We illustrate the indispensability of the mapping of rhythm characteristics in broader structures, chronomes, along several or all available different time...