Circadian clock precision, health, and longevity

An accurate circadian clock, associated with the precise intrinsic period, tau, can be linked with a definite chronotype and health status. Exemplified by different animal species, and, as we argue herein, may as well be in humans, endogenous tau close enough to 24 hours is associated with higher life expectancy, lower morbidity, and is possibly adhered to moderate morning chronotype. Accurate circadian tau facilitates maintaining a high amplitude of circadian rhythms, a phenotypic trait that is related to health and longevity. Some genetic factors that coordinate tau and ensure circadian clock precision is considered.

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Circadian Rhythm: Potential Therapeutic Target for Atherosclerosis and Thrombosis

International Journal of Molecular Sciences ◽

10.3390/ijms22020676 ◽

2021 ◽

Vol 22 (2) ◽

pp. 676

Author(s):

Andy W. C. Man ◽

Huige Li ◽

Ning Xia

Keyword(s):

Circadian Rhythm ◽

Cardiovascular Diseases ◽

Circadian Rhythms ◽

Circadian Clock ◽

Therapeutic Target ◽

Environmental Changes ◽

Clock Genes ◽

Vascular System ◽

Peripheral Tissues ◽

Inflammatory Processes

Every organism has an intrinsic biological rhythm that orchestrates biological processes in adjusting to daily environmental changes. Circadian rhythms are maintained by networks of molecular clocks throughout the core and peripheral tissues, including immune cells, blood vessels, and perivascular adipose tissues. Recent findings have suggested strong correlations between the circadian clock and cardiovascular diseases. Desynchronization between the circadian rhythm and body metabolism contributes to the development of cardiovascular diseases including arteriosclerosis and thrombosis. Circadian rhythms are involved in controlling inflammatory processes and metabolisms, which can influence the pathology of arteriosclerosis and thrombosis. Circadian clock genes are critical in maintaining the robust relationship between diurnal variation and the cardiovascular system. The circadian machinery in the vascular system may be a novel therapeutic target for the prevention and treatment of cardiovascular diseases. The research on circadian rhythms in cardiovascular diseases is still progressing. In this review, we briefly summarize recent studies on circadian rhythms and cardiovascular homeostasis, focusing on the circadian control of inflammatory processes and metabolisms. Based on the recent findings, we discuss the potential target molecules for future therapeutic strategies against cardiovascular diseases by targeting the circadian clock.

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Changing Mortality and Morbidity Rates and the Health Status and Life Expectancy of the Older Population

Demography ◽

10.2307/2061913 ◽

1994 ◽

Vol 31 (1) ◽

pp. 159 ◽

Cited By ~ 161

Author(s):

Eileen M. Crimmins ◽

Mark D. Hayward ◽

Yasuhiko Saito

Keyword(s):

Health Status ◽

Life Expectancy ◽

Older Population ◽

Mortality And Morbidity

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Cryptochromes regulate IGF-1 production and signaling through control of JAK2-dependent STAT5B phosphorylation

Molecular Biology of the Cell ◽

10.1091/mbc.e16-08-0624 ◽

2017 ◽

Vol 28 (6) ◽

pp. 834-842 ◽

Cited By ~ 14

Author(s):

Amol Chaudhari ◽

Richa Gupta ◽

Sonal Patel ◽

Nikkhil Velingkaar ◽

Roman Kondratov

Keyword(s):

Circadian Rhythms ◽

Circadian Clock ◽

Skeletal Muscles ◽

Cancer Metabolism ◽

Reduced Body ◽

Circadian Control ◽

Cell Growth And Proliferation ◽

Deficient Mice ◽

Igf Signaling

Insulin-like growth factor (IGF) signaling plays an important role in cell growth and proliferation and is implicated in regulation of cancer, metabolism, and aging. Here we report that IGF-1 level in blood and IGF-1 signaling demonstrates circadian rhythms. Circadian control occurs through cryptochromes (CRYs)—transcriptional repressors and components of the circadian clock. IGF-1 rhythms are disrupted in Cry-deficient mice, and IGF-1 level is reduced by 80% in these mice, which leads to reduced IGF signaling. In agreement, Cry-deficient mice have reduced body (∼30% reduction) and organ size. Down-regulation of IGF-1 upon Cry deficiency correlates with reduced Igf-1 mRNA expression in the liver and skeletal muscles. Igf-1 transcription is regulated through growth hormone–induced, JAK2 kinase–mediated phosphorylation of transcriptional factor STAT5B. The phosphorylation of STAT5B on the JAK2-dependent Y699 site is significantly reduced in the liver and skeletal muscles of Cry-deficient mice. At the same time, phosphorylation of JAK2 kinase was not reduced upon Cry deficiency, which places CRY activity downstream from JAK2. Thus CRYs link the circadian clock and JAK-STAT signaling through control of STAT5B phosphorylation, which provides the mechanism for circadian rhythms in IGF signaling in vivo.

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PEPTIDE REGULATES HUMAN CIRCADIAN RHYTHMS GENES EXPRESSION DURING PINEAL GLAND ACCELERATED AGING

Успехи геронтологии ◽

10.34922/ae.2020.33.3.002 ◽

2020 ◽

pp. 429-435

Author(s):

О. М. Ивко ◽

Н. С. Линькова ◽

А. Р. Ильина ◽

А. А. Шарова ◽

Г. А. Рыжак

Keyword(s):

Circadian Rhythms ◽

Pineal Gland ◽

Circadian Clock ◽

Peripheral Blood ◽

Accelerated Aging ◽

Peripheral Blood Lymphocytes ◽

Circadian Genes ◽

Blood Lymphocytes ◽

Aged People ◽

Genes Expression

Ночная работа приводит к десинхронизации биоритмов, нарушению мелатонинобразующей функции и ускоренному старению эпифиза человека. Одним из перспективных геропротекторов, восстанавливающих синтез эпифизарного мелатонина, является пептид AEDG ( Ala-Glu-Asp-Gly ). Последний в 1,7 раза повышает экскрецию 6-сульфатоксимелатонина в моче людей среднего возраста, у которых этот показатель исходно снижен. Кроме того, у людей со сниженной мелатонинобразующей функцией эпифиза, пептид AEDG нормализует повышенную экспрессию циркадных генов Clock и Csnk 1 e в лейкоцитах и в 2 раза повышает сниженную экспрессию гена Cry 2 в лимфоцитах крови. В основе геропротекторного эффекта пептида AEDG лежит его способность восстанавливать мелатонинобразующую функцию эпифиза через регуляцию экспрессии часовых генов человека. Night work provides biorhythms desynchronization, disorder of melatonin-producing function and accelerated pineal gland aging. One of the promising geroprotectors restoring the pineal melatonin synthesis is the AEDG ( Ala-Glu-Asp-Gly ) peptide. AEDG peptide increases in 1,7 times the 6-sulfatoxymelatonin (6-SOMT) excretion in the urine of middle-aged people. Moreover, AEDG peptide normalized circadian Clock and Csnk1e genes hyper expression in leukocytes in 1,9-2,1 times and increases the Cry 2 gene hypo expression in peripheral blood lymphocytes in 2 times in people with reduced melatonin-producing epiphysis function. The geroprotective effect of the AEDG peptide is based on its ability to restore the epiphysis melatonin-producing function by means regulation of human circadian genes expression.

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Survival is reduced when endogenous period deviates from 24 h in a non-human primate, supporting the circadian resonance theory

Scientific Reports ◽

10.1038/s41598-020-75068-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Clara Hozer ◽

Martine Perret ◽

Samuel Pavard ◽

Fabien Pifferi

Keyword(s):

Circadian Rhythms ◽

Circadian Clock ◽

Microcebus Murinus ◽

Circadian Period ◽

Biological Functions ◽

Resonance Theory ◽

Aging Research ◽

Mouse Lemurs ◽

Living Organisms ◽

Human Primate

Abstract Circadian rhythms are ubiquitous attributes across living organisms and allow the coordination of internal biological functions with optimal phases of the environment, suggesting a significant adaptive advantage. The endogenous period called tau lies close to 24 h and is thought to be implicated in individuals’ fitness: according to the circadian resonance theory, fitness is reduced when tau gets far from 24 h. In this study, we measured the endogenous period of 142 mouse lemurs (Microcebus murinus), and analyzed how it is related to their survival. We found different effects according to sex and season. No impact of tau on mortality was found in females. However, in males, the deviation of tau from 24 h substantially correlates with an increase in mortality, particularly during the inactive season (winter). These results, comparable to other observations in mice or drosophila, show that captive gray mouse lemurs enjoy better fitness when their circadian period closely matches the environmental periodicity. In addition to their deep implications in health and aging research, these results raise further ecological and evolutionary issues regarding the relationships between fitness and circadian clock.

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Mortality level and trend in South Africa and their Implications

Demography and social economy ◽

10.15407/dse2021.01.053 ◽

2021 ◽

pp. 53-62

Author(s):

K. A. KYEI ◽

P. GAVHI

Keyword(s):

South Africa ◽

Health Status ◽

Infant Mortality ◽

Life Expectancy ◽

South African ◽

Household Survey ◽

Infant Mortality Rate ◽

Critical Measure ◽

Study Results ◽

Credible Information

Mortality is a critical measure of population’s health and public health systems. Infant mortality, for example, indicates quality of life, accessibility to primary healthcare and the overall health status of a country. Reduction in infant mortality shows improvement in the health status. No credible information about mortality in South Africa because the two previous censuses’ data from Statistics South Africa (StatsSA) were not reliable, this study makes attempt to bridge the gap in the lack of knowledge. Th is study uses South African General Household Survey (SAGHS) data, to fi nd the level and trend of mortality and their implications. Data for the years, 2012, 2013 and 2015, have been used. Demographic and statistical methods, including an evaluation of data quality using UN joint score, and construction of model life tables. The results indicated that the infant mortality rate (IMR) was 43 per 1000 in 2012, 36 per 1000 in 2013 and 21 per 1000 in 2015. Th is study further indicated that the general health status of South African population improved marginally from 2012 to 2015 because the life expectancy in creas ed by 7 years for the males, and by 8 years for females, between those years. The study results that SAGHS data are reliable, mortality is decreasing with increasing life expectancy. The study recommends that more proactive measures need to be put in place to improve the health status of the population, especially the children because the IMR is still quite high and creates concerns.

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Interaction between photoperiod and variation in circadian rhythms in tomato

10.1101/2022.01.14.476322 ◽

2022 ◽

Author(s):

Yanli Xiang ◽

Thomas Sapir ◽

Pauline Rouillard ◽

Marina Ferrand ◽

Jose M Jimenez-Gomez

Keyword(s):

Seasonal Variation ◽

Circadian Rhythms ◽

Phase Shift ◽

Circadian Clock ◽

Environmental Changes ◽

Circadian Clocks ◽

Biological Processes ◽

Near Isogenic Lines ◽

Transcriptomic Profiling ◽

Isogenic Lines

Many biological processes follow circadian rhythmicity and are controlled by the circadian clock. Predictable environmental changes such as seasonal variation in photoperiod can modulate circadian rhythms, allowing organisms to adjust to the time of the year. Modification of circadian clocks is especially relevant in crops to enhance their cultivability in specific regions by changing their sensibility to photoperiod. In tomato, the appearance of mutations in EMPFINDLICHER IM DUNKELROTEN LICHT 1 (EID1, Solyc09g075080) and NIGHT LIGHT-INDUCIBLE AND CLOCK-REGULATED GENE 2 (LNK2, Solyc01g068560) during domestication delayed its circadian rhythms, and allowed its expansion outside its equatorial origin. Here we study how variation in circadian rhythms in tomato affects its perception of photoperiod. To do this, we create near isogenic lines carrying combinations of wild alleles of EID1 and LNK2 and perform transcriptomic profiling under two different photoperiods. We observe that EID1, but not LNK2, has a large effect on the tomato transcriptome and its response to photoperiod. This large effect of EID1 is likely a consequence of the global phase shift elicited by this gene in tomato's circadian rhythms.

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Modulatory Effects of Circadian Rhythms in the Lung Adenocarcinoma Tumor Microenvironment

10.21203/rs.3.rs-838444/v1 ◽

2021 ◽

Author(s):

Qianzhun Huang ◽

Xiaoyang Su ◽

Ning Fang ◽

Jian Huang

Keyword(s):

Tumor Microenvironment ◽

Circadian Rhythms ◽

Lung Adenocarcinoma ◽

Circadian Clock ◽

Drug Sensitivity ◽

Molecular Mechanisms ◽

Clock Genes ◽

Functional Enrichment ◽

Expression Levels ◽

Circadian Clock Genes

Abstract Background: Dysregulated circadian dynamic balance is strongly associated with cancer development. However, biological functions of circadian rhythms in lung adenocarcinoma (LUAD) have not been elucidated. This study aimed at valuating the modulatory effects of circadian rhythms in the LUAD tumor microenvironment.Methods: Multiple open-source bioinformatics research platforms are used to comprehensively elucidate the expression level, prognosis, potential biological function, drug sensitivity, and immune microenvironment of circadian clock genes in LUAD.Results: Most circadian clock genes in LUAD are dysregulated and are strongly correlated with patient prognosis, and missense mutations at splicing sites of these genes. Besides, these genes are closely associated with some well-known cancer-related marker pathways, which are mainly involved in the inhibition of the Apoptosis, Cell cycle, and DNA Damage Response Pathway. Furthermore, functional enrichment analysis revealedthat circadian clock genes regulate transcription factor activities and circadian rhythms in LUAD tissues. As for drug sensitivity, high expression of CLOCK, CRY1, and NR1D2 as well as suppressedPER2 and CRY2 expression levels are associated with drug resistance. The expression levels of circadian clock genes in LUAD correlate with immune infiltration and are involved in the regulation of immunosuppression.Conclusions: Our multi-omics analysis provides a more comprehensive understanding of the molecular mechanisms of the circadian clock genes in LUAD and provides new insights for a more precise screening of prognostic biomarkers and immunotherapy.

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Time-of-day-dependent responses of cyanobacterial cellular viability against oxidative stress

10.1101/851774 ◽

2019 ◽

Author(s):

Kenya Tanaka ◽

Ginga Shimakawa ◽

Shuji Nakanishi

Keyword(s):

Oxidative Stress ◽

Circadian Rhythms ◽

Cell Viability ◽

Circadian Clock ◽

Stress Tolerance ◽

Time Of Day ◽

Circadian Oscillation ◽

Subjective Time ◽

Rhythmic Pattern ◽

Oxidative Stress Tolerance

AbstractAs an adaptation to periodic fluctuations of environmental light, photosynthetic organisms have evolved a circadian clock. Control by the circadian clock of many cellular physiological functions, including antioxidant enzymes, metabolism and the cell cycle, has attracted attention in the context of oxidative stress tolerance. However, since each physiological function works in an integrated manner to deal with oxidative stress, whether or not cell responses to oxidative stress are under circadian control remains an open question. In fact, circadian rhythms of oxidative stress tolerance have not yet been experimentally demonstrated. In the present work, we applied an assay using methyl viologen (MV), which generates reactive oxygen species (ROS) under light irradiation, and experimentally verified the circadian rhythms of oxidative stress tolerance in photosynthetic cells of the cyanobacterium Synechococcus elongatus PCC7942, a standard model species for investigation of the circadian clock. Here, we report that ROS generated by MV treatment causes damage to stroma components and not to the photosynthetic electron transportation chain, leading to reduced cell viability. The degree of decrease in cell viability was dependent on the subjective time at which oxidative stress was applied. Thus, oxidative stress tolerance was shown to exhibit circadian rhythms. In addition, the rhythmic pattern of oxidative stress tolerance disappeared in mutant cells lacking the essential clock genes. Notably, ROS levels changed periodically, independent of the MV treatment. Thus, we demonstrate for the first time that in cyanobacterial cells, oxidative stress tolerance shows circadian oscillation.

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Health Status of Old Age Population in Bulgaria

European Journal of Interdisciplinary Studies ◽

10.26417/ejis.v2i4.p126-131 ◽

2016 ◽

Vol 2 (4) ◽

pp. 126

Author(s):

Mariana Mourgova

Keyword(s):

Health Status ◽

Life Expectancy ◽

European Countries ◽

Healthy Life Expectancy ◽

Mortality Data ◽

Healthy Life ◽

Healthy Life Years ◽

Demographic Indicators ◽

Life Years ◽

Different Levels

This article examines the health status of the population in Bulgaria at age 65 by gender during the period 2006-2014. The health status is examined by some of the most frequently used demographic indicators, namely life expectancy, based on mortality data and healthy life years and healthy life expectancy, based on mortality, life expectancy and self-perceived health. The main results show that despite of the observed increase in life expectancy at age 65 in Bulgaria during the period it is the lowest compared to other European countries. The share for both men and women reported their health status as without limitations in respect to daily activities decline, while those reported their health status as good increase. These contradictory facts reflect on the measures of health status. Thus, the trend in healthy life years for both sexes decline over the period, whereas the trend in healthy life expectancy increases. Compared with the other European countries, the expected number of years without limitations in Bulgaria is among the largest, while the healthy life expectancy is the lowest. These differences could be explained by the different levels in mortality and the nature of the measures of health status themselves.

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