Browsing by Subject "Circadian rhythms"
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- PublicationRestrictedAge-related changes in fatty acid profile and locomotor activity rhythms in Nothobranchius korthausae(Elsevier, 2011-08-28) Lucas-Sanchez, A; Almaida Pagán, Pedro Francisco; Madrid, Juan A; Costa, J. de; Mendiola, P; FisiologíaThe life cycle of Nothobranchius korthausae, a Cyprinodontiformes fish, was studied in our laboratory to characterise the ageing process. Some morphological changes, such as spine curvature, skin colour, and fin and eye appearance are described. Growth and survival curves reflected a fast life cycle with rapid initial growth until 4 weeks of age, after which the fish grew more slowly before reaching their final size in week 40. Senescence onset was established at week 48 with a decrease in spawn size and viability and a general decline in the animal's appearance (weight and colouration losses, caudal fin degradation, and cataractogenesis). The fatty acid composition changed with age,with high unsaturation in the adult stage as reflected by a high peroxidation index, a condition that is associated with high susceptibility to oxidative damage if elevated reactive oxygen species (ROS) production occurs. Senescent fish had an increase in monounsaturated fatty acid proportions and a lower peroxidation index (226.5±19.7 in adults versus 120.2±19.1 in senescent fish, Pb0.05). The circadian system, as reflected by locomotor activity rhythms, showed noticeable changes with age. Twenty-four-week-old fish (adults) had a robust diurnal rhythm that showed a decrease in total activity, an increase in rhythmfragmentation, and a fall in amplitude and regularity with age. Changes were clearly reflected in the Circadian Function Index variations (0.56, 0.47 and 0.25 at 24, 48 and 72 weeks of age, respectively). In conclusion, N. korthausae appears to be a species with appropriate characteristics for ageing studies because it manifests clear signs of progressive ageing. Comparing species of Nothobranchius genus with different lifespans may be useful for increasing our understanding of the ageing process.
- PublicationOpen AccessAutoradiographic investigation of circadian rhythms in alveolar bone periosteum and cementum in young mice(Murcia : F. Hernández, 1987) Tonna, E.A.; Singh, I.J.; Sandhu, H.S.This report presents circadian rhythms in cell proliferation of alveolar bone periosteum and cementum of the maxillary first molars of male 5-week-old BNL, Swiss albino mice which were maintained on a 12 hr light1 dark cycle. Mice were injected with 3H-TDR (lucilgm. body wt.) 1 hr prior to sacrifice and killed every 3 hrs for 24 hrs starting at 9 a.m. Maxillae were decalcified, routinely processed histologically and autoradiographs prepared. Cell labeling indices of alveolar bone and cementum mesial to the first molar were determined. Alveolar bone periosteal and cemental cells show circadian rhythm in their DNA synthetic processes. Peaks in percent labeling exhibit higher values than previously reported for nontraumatized, normal dental periosteum and cementum. While the outer periosteum reveals a single 24 hr peak (6 p.m.), inner periosteum and cementum reveal two ultradian peaks 9 to 12 hrs apart involving both light and dark periods. Rodents are nocturnal, but high peaks are also evident in the light periods, consequently, not all peaks are synonymous with the period of animal activity and feeding. Although the single daylight peak of the outer periosteum may indicate growth of that surface at night to about noon, the double peaks exhibited by inner periosteum and cementum indicate lightldark, continuously active surfaces in terms of DNA synthesis and growth
- PublicationEmbargoChronodisruption and ambulatory circadian monitoring in cancer patients: beyond the body clock(Springer, 2022-01-21) Almaida Pagán, Pedro Francisco; Torrente, Maria; Campos Martínez, Manuel; Provencio, Mariano; Madrid, Juan A; Franco, Fabio; Rodriguez Morilla, Beatriz; Cantos, Blanca; Sousa, Pedro A; Martinez Madrid, Maria J; Pimentao, Joao; Rol, Maria A; FisiologíaPurpose of Review Circadian rhythms impose daily rhythms a remarkable variety of metabolic and physiological functions, such as cell proliferation, inflammation, and DNA damage response. Accumulating epidemiological and genetic evidence indicates that circadian rhythms’ disruption may be linked to cancer. The integration of circadian biology into cancer research may offer new options for increasing cancer treatment effectiveness and would encompass the prevention, diagnosis, and treatment of this disease. Recent Findings In recent years, there has been a significant development and use of multi-modal sensors to monitor physical activity, sleep, and circadian rhythms, allowing, for the very first time, scaling accurate sleep monitoring to epidemiological research linking sleep patterns to disease, and wellness applications providing new potential applications. Summary This review highlights the role of circadian clock in tumorigenesis, cancer hallmarks and introduces the stateof-the-art in sleep-monitoring technologies, discussing the eventual application of insights in clinical settings and cancer research.
- PublicationOpen AccessChronodisruption and ambulatory circadian monitoring in cancer patients: beyond the body clock(Springer, 2022-01-21) Almaida Pagan, Pedro F.; Torrente, María; Campos Martínez, Manuel; Provencio, Mariano; Madrid, Juan Antonio; Franco, Fabio; Rodríguez Morilla, Beatriz; Cantos, Blanca; Sousa, Pedro A.; Martínez Madrid, María José; Pimentao, Joao; Rol de Lama, María de los Ángeles; FisiologíaPurpose of ReviewCircadian rhythms impose daily rhythms a remarkable variety of metabolic and physiological functions, such as cell proliferation, inflammation, and DNA damage response. Accumulating epidemiological and genetic evidence indicates that circadian rhythms’ disruption may be linked to cancer. The integration of circadian biology into cancer research may offer new options for increasing cancer treatment effectiveness and would encompass the prevention, diagnosis, and treatment of this disease.Recent FindingsIn recent years, there has been a significant development and use of multi-modal sensors to monitor physical activity, sleep, and circadian rhythms, allowing, for the very first time, scaling accurate sleep monitoring to epidemiological research linking sleep patterns to disease, and wellness applications providing new potential applications.SummaryThis review highlights the role of circadian clock in tumorigenesis, cancer hallmarks and introduces the state-of-the-art in sleep-monitoring technologies, discussing the eventual application of insights in clinical settings and cancer research.
- ItemOpen AccessDifferential expression of ferroptosis markers, circadian regulators, KLOTHO, and classical tumor suppressors in colorectal cancer according to tumor stage: Influence of age, anatomical location, and correlation patterns(2025) Cielo Garcia Montero; Oscar Fraile Martinez; Ana M. Minaya Bravo; Diego Liviu Boaru; Diego De Leon Oliva; Patricia De Castro Martinez; Majd N. Michael Alhaddadin; Silvestra Barrena Blázquez; Laura Lopez Gonzalez; Luis G. Guijarro; Natalio Garcia Honduvilla; Víctor Roberto Baena Romero; Carlos Daniel Padilla Ansala; Mar Royuela; María Del Val Toledo Lobo; Leonel Pekarek; Roberto Fernández Baillo Gallego de la Sacristana; Mauricio Hernández Fernández; Montserrat Chao Crecente; Melchor Alvarez-Mon; Raul Diaz-Pedrero; Miguel A. Ortega; Miguel A. Saez; Biología Celular e HistologíaColorectal cancer (CRC) is a leading cause of cancer-related mortality, with an incidence projected to rise significantly worldwide. While TNM staging remains the cornerstone of prognosis and treatment decisions, additional biomarkers are needed to enhance predictive accuracy and therapeutic targeting. Ferroptosis, an iron-dependent cell death pathway, has emerged as a key regulator of CRC progression and therapy resistance. Circadian rhythms, KLOTHO, and tumor suppressors, such as p53, CDKN1A (p21), and Rb, also play crucial roles in CRC biology. Integrating TNM staging with molecular markers and patient-specific variables offers a more precise, personalized approach to CRC management. In the present work, we analyze the histopathological expression of KLOTHO, ferroptosis markers (TFRC, ALOX-5, ACSL-4, and GPX-4), circadian regulators (CLOCK, BMAL1, PER1, and PER2), and classical tumor suppressors (p53, p21, and Rb) in a cohort of 63 patients diagnosed with CRC. Besides, we have considered important clinical variables, like sex, age, and anatomical location, in our statistical analysis; correlation with the protein expression of these markers was also included for each stage (T1, T2, and T3). Our study reveals that advanced CRC stages (primarily T3) exhibit increased expression of ferroptosis markers (TFRC, ALOX5, ACSL4, and GPX4) and tumor suppressors (p53, p21, and Rb), alongside reduced histopathological detection of KLOTHO and circadian markers (BMAL1, CLOCK, PER1, and PER2) compared with earlier stages. Age, but not sex, influenced the expression of several markers. Tumor location also played a role, with right-sided CRCs showing significant stage-related differences in ferroptosis, tumor suppressor, and BMAL1, whereas left-sided tumors exhibited variations primarily in circadian markers (CLOCK, PER1, and PER2). Correlation analyses across tumor stages indicate dynamic shifts, with tumor suppressors maintaining positive associations with ferroptosis markers and anti-aging/circadian markers showing stage-dependent changes. Despite the inherent limitations of our study, these findings highlight the evolving biomarker landscape in CRC progression, although further research is needed to elucidate their clinical implications.
- PublicationOpen AccessEvaluating the Accuracy of Declared Eating Schedules by Continuous Glucose Monitoring(2026-02-27) González Romero, Pedro; Madrid Pérez, Juan Antonio; Almaida Pagán, Pedro Francisco; Rol de Lama, María de los Ángeles; Sin departamento asociado; Facultades de la UMU::Facultad de BiologíaBackground/Objectives: Chrononutrition is an emergent field concerning the effect of eating patterns on human health and their relationship with biological rhythms. Current evidence points towards the benefits of early eating in the prevention of non-communicable diseases and circadian health. Despite the importance of eating/fasting rhythm, current methods are neither specific nor validated against physiological variables. This work aimed to explore an objective metabolic outcome, postprandial glucose, as an accuracy indicator of self-declared meal schedules registered in a mobile app. Methods: A 1-week protocol of ambulatory monitoring of meal schedules, glucose, and circadian variables was performed in 20 young adults. Meal annotations were registered using KronoEat 1.0, a smartphone app, allowing for both prospective and recall entries. A circadian monitoring device provided data on movement intensity, distal skin temperature, and prospective food annotation. Results: Participants annotated an average of 3.5 food events/day/participant with KronoEat. Breakfast (92.7%) and lunch (86.4%) showed the highest proportion of food events related to a glycemic excursion, whereas this proportion was lower for dinner (79.7%) and snacks (67.7%). Postprandial glucose after main meals differed significantly from average glucose levels. Interesting couplings were found in circadian variables and glucose—for example, between post-breakfast glycemic excursions and the morning increase in activity. Conclusions: Meal schedules registered under free-living conditions in KronoEat show high levels of correlation with postprandial glucose and glycemic excursions derived from continuous glucose monitoring.
- PublicationRestrictedInfluence of circadian rhythms on sports performance(2021-06-01) Ayala, Victoria; Martínez-Bebia, Manuel; Latorre, Jose Antonio; Gimenez-Blasi, Nuria; Jimenez-Casquet, Maria Jose; Conde-Pipo, Javier; Bach-Faig, Anna; Mariscal-Arcas, Miguel; Tecnología de Alimentos, Nutrición y BromatologíaChronobiology is the scienti!c discipline of study of biological rhythms, a term that has gained ground in the sports world. Recently numerous studies have indicated that the time of day in which sports are practiced in"uences the achievement of good physical performance. The aim of this review was to study the relationship between circadian rhythms and physical performance, accord ing to the latest published data. In addition, the physiological processes involved in the physical response and the di#erences according to the type of sport and athletes’ characteristics were studied. A bibliographic search was carried out through !ve databases (Pubmed, Scopus, Researcher Gate, Google Scholar, UOC Library), focusing on articles published in the last ten years and written in English and Spanish. 36 papers met the inclusion criteria. Body temperature is a factor that shows a circadian pattern with a marked peak in the later afternoon, time of the day at which physical performance is at its highest, i.e. speed, agility, distance covered, jumping power. The perception of e#ort is also higher in the afternoon. Regarding the chronotype, evening types seem to be the most a#ected to do sports out of their optimal time-of-day. The tendency shows more morning types as age increases. Training sessions should be planned according to the optimal time of day for each athlete. It’s essential to take into account individual chronotype. The desyn chronization of circadian rhythms can cause a decrease in physical performance.
- PublicationEmbargoIntegral Analysis of Circadian Rhythms(Yolanda Larriba, 2023-08-10) Vicente-Martinez, J; Almaida Pagán, Pedro Francisco; Martinez-Nicolas, A; Madrid, Juan A; Rol, M A; Bonmatí Carrión, María de los Ángeles; Fisiología; Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable, Instituto de Salud Carlos III, Madrid, SpainOur biological processes do not present a static and steady picture. Instead, most of these processes oscillate throughout the 24-h day. The system that controls this circadian rhythmicity is composed of a central pacemaker and peripheral oscillators that rely on inputs and produce outputs that can be measured through appropriate techniques. The correct measurement and analysis of the func-tioning of each part of the circadian system are becoming essential in many fields of biomedicine. In this chapter, we will cover the entire process, from the acquisition of circadian data to their analyses through parametric and non-parametric methods, including the dynamic modeling of different circadian processes.
- PublicationOpen AccessIntrinsically synthesized melatonin in mitochondria and factors controlling its production(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Reiter, Russel J.; Sharma, Ramaswamy N; Almieda Chuffa, Luiz Gustavo de; Silva, Danilo Grunig Humberto da Silva; Rosales Corral, SergioThe percentage of the total amount of melatonin produced in vertebrates that comes from the pineal is small (likely <5%) but, nevertheless, functionally highly noteworthy. The significance of pineal melatonin is that it is secreted cyclically such that it has a critical function in influencing not only the suprachiasmatic nucleus but clock genes that reside in perhaps every cell throughout the organism. Extrapineal melatonin, which may be synthesized in the mitochondria of all other cells in much larger amounts than that in the pineal gland has a different function than that derived from the pineal gland. Its synthesis is not circadian and it is not directly impacted by the photoperiodic environment. Also, melatonin from the extrapineal sites is not normally secreted into the blood stream; rather, it acts locally in its cell of synthesis or, possibly via paracrine mechanisms, on immediately adjacent cells. The functions of extrapineal melatonin include central roles in maintaining molecular and redox homeostasis and actions in resisting pathological processes due to its ability to directly or indirectly detoxify free radicals. The vast majority of organisms that exist on Earth lack a pineal gland so pineal-derived melatonin is unique to vertebrates. Evidence suggests that all invertebrates, protists and plants synthesized melatonin and they have no pineal homolog; thus, the production of melatonin by extrapineal cells in vertebrates should not be unexpected. While the factors that control pineal melatonin synthesis are well documented, the processes that regulate extrapineal melatonin production are undefined.
- PublicationOpen AccessLiving at the wrong time: effects of unmatching official time in Portugal and western Spain(MDPI, 2022-07-28) Casado Ramírez, Elvira; Moreno Casbas, María Teresa; Campos Martínez, Manuel; ModulEN Consortium; Madrid, Juan Antonio; Rol de Lama, María de los Ángeles; Bonmatí Carrión, María de los Ángeles; FisiologíaHuman circadian rhythmicity is subjected to the internal circadian clock, the sun and social clocks (official time, social/work schedules). The discrepancy among these clocks, as occurs when official time does not match its geographical time zone, may produce circadian disruption. Western Spain (GMT+1/+2) and Portugal (GMT0/+1) share similar longitudes (sun time) but have different official times. This provides a unique opportunity to evaluate the effects of official time on circadian rhythmicity and sleep in elderly and retired populations (with no remunerated duties presumed, although other social commitments may be present) at both locations. Although both populations slept enough for their age (7–8 h), circadian robustness (e.g., interdaily stability, relative amplitude) was greater in Portugal, especially during weekdays, while greater desynchronization (both body temperature vs. motor activity and body temperature vs. light exposure) tended to occur in the Spaniards. Once corrected by GMT0, meals took place later in Spain than in Portugal, especially as the day progresses, and a possible interplay between bed/meal timings and internal desynchronization was found. Our results point to the possible deleterious effect on circadian system robustness when official time is misaligned with its geographical time zone.
- PublicationOpen AccessMid-luteal phase progesterone effects on vigilance tasks are modulated by women’s chronotype(Elsevier, 2022-03-12) Palmero Jara, Lucía Beatriz; Tortajada Gomariz, Miriam; Campoy Menéndez, Guillermo; Fuentes Melero, Luis José; Martínez Pérez, Víctor; Psicología Básica y MetodologíaBackground In this study we assessed the effects of progesterone on vigilance tasks that require sustained attention. In contrast to previous research, we differentiated two components of vigilance: the exogenous component, involved in monotonous and tedious tasks such as the Psychomotor Vigilance Task (PVT); and the endogenous component, involved in tasks that require cognitive control such as the Sustained Attention to Response Task (SART). Methods A sample of 32 female participants differing in extreme chronotypes were tested at their optimal and non-optimal time-of-day, as secretion of sex hormones follows biological rhythms. Ovulation tests that measure the presence of luteinizing hormone (LH) in urine were used to minimize methodological errors. Women of Morning-type or Evening-type chronotypes completed 4 experimental sessions of the two attentional tasks when they were in their follicular (low progesterone level) and mid-luteal (high progesterone level) phases, both in the morning (8:00 AM) and the evening (8:30 PM). Results Compared with the follicular phase, performance in the mid-luteal phase improved in the Morning-type participants and worsened in the Evening-type participants. This pattern of results was observed only when testing occurred at the optimal time-of-day and with both the PVT and the SART tasks. Conclusion These results suggest that the simultaneous presence of both progesterone and cortisol at 8:00 AM may explain the benefit observed in Morning-type females. In contrast, the low concentration of cortisol along with the reduced benefit of mid-luteal phase progesterone in the evening may account for the worsening in performance observed in Evening-type females.
- PublicationOpen AccessPhase response curve to Light under ambulatory conditions: a pilot study for potential application to caylight saving time transitions(MDPI, 2022-10-28) Arguelles Prieto, Raquel; Madrid, Juan Antonio; Rol de Lama, María de los Ángeles; Bonmatí Carrión, María de los Ángeles; FisiologíaSeveral studies have investigated the relationship between daylight saving time (DST) and sleep alterations, psychiatric disorders, cardiovascular events and traffic accidents. However, very few have monitored participants while maintaining their usual lifestyle before and after DST. Considering that DST transitions modify human behavior and, therefore, people’s light exposure patterns, the aim of this study was to investigate the potential effects of DST on circadian variables, considering sleep and, for the first time, the human phase response curve to light. To accomplish this, eight healthy adults (33 ± 11 years old, mean ± SD) were recruited to monitor multivariable circadian markers and light exposure by means of a wearable ambulatory monitoring device: Kronowise®. The following night phase markers were calculated: midpoints of the five consecutive hours of maximum wrist temperature (TM5) and the five consecutive hours of minimum time in movement (TL5), sleep onset and offset, as well as sleep duration and light intensity. TM5 for wrist temperature was set as circadian time 0 h, and the balance between advances and delays considering the phase response curve to light was calculated individually before and after both DST transitions. To assess internal desynchronization, the possible shift in TM5 for wrist temperature and TL5 for time in movement were compared. Our results indicate that the transition to DST seems to force the circadian system to produce a phase advance to adapt to the new time. However, the synchronizing signals provided by natural and personal light exposure are not in line with such an advance, which results in internal desynchronization and the need for longer synchronization times. On the contrary, the transition back to ST, which implies a phase delay, is characterized by a faster adaptation and maintenance of internal synchronization, despite the fact that exposure to natural light would favor a phase advance. Considering the pilot nature of this study, further research is needed with higher sample sizes.
- PublicationOpen AccessRelationship between human pupillary light reflex and circadian system status(Public Library of Science, 2016-09-16) Hild, Konstanze; Isherwood, Cheryl; Sweeney, Stephen J.; Revell, Victoria L.; Skene, Debra J.; Rol, Maria Ángeles; Madrid, Juan Antonio; Bonmatí Carrión, María de los Ángeles; Anatomía Humana y PsicobiologíaIntrinsically photosensitive retinal ganglion cells (ipRGCs), whose photopigment melanopsin has a peak of sensitivity in the short wavelength range of the spectrum, constitute a common light input pathway to the olivary pretectal nucleus (OPN), the pupillary light reflex (PLR) regulatory centre, and to the suprachiasmatic nuclei (SCN), the major pacemaker of the circadian system. Thus, evaluating PLR under short wavelength light (λmax 500 nm) and creating an integrated PLR parameter, as a possible tool to indirectly assess the status of the circadian system, becomes of interest. Nine monochromatic, photon-matched light stimuli (300 s), in 10 nm increments from λmax 420 to 500 nm were administered to 15 healthy young participants (8 females), analyzing: i) the PLR; ii) wrist temperature (WT) and motor activity rhythms (WA), iii) light exposure (L) pattern and iv) diurnal preference (HorneÖstberg), sleep quality (Pittsburgh) and daytime sleepiness (Epworth). Linear correlations between the different PLR parameters and circadian status index obtained from WT, WA and L recordings and scores from questionnaires were calculated. In summary, we found markers of robust circadian rhythms, namely high stability, reduced fragmentation, high amplitude, phase advance and low internal desynchronization, were correlated with a reduced PLR to 460–490 nm wavelengths. Integrated circadian (CSI) and PLR (cp-PLR) parameters are proposed, that also showed an inverse correlation. These results demonstrate, for the first time, the existence of a close relationship between the circadian system robustness and the pupillary reflex response, two non-visual functions primarily under melanopsin-ipRGC input.