Circadian clocks, ageing and age-related diseases

2016 ◽  
Author(s):  
Qing-Jun Meng
Keyword(s):  
Circadian Clocks ◽  
Age Related

scholarly journals The intervertebral disc contains intrinsic circadian clocks that are regulated by age and cytokines and linked to degeneration

2016 ◽  
Vol 76 (3) ◽  
pp. 576-584 ◽  
Author(s):  
Michal Dudek ◽  
Nan Yang ◽  
Jayalath PD Ruckshanthi ◽  
Jack Williams ◽  
Elzbieta Borysiewicz ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Clock Gene ◽  
Ex Vivo ◽  
Conditional Knockout ◽  
Circadian Clocks ◽  
Diurnal Rhythms ◽  
Tissue Specific ◽  
Age Related ◽  
Disc Cells ◽  
Ivd Degeneration

ObjectivesThe circadian clocks are internal timing mechanisms that drive ∼24-hour rhythms in a tissue-specific manner. Many aspects of the physiology of the intervertebral disc (IVD) show clear diurnal rhythms. However, it is unknown whether IVD tissue contains functional circadian clocks and if so, how their dysregulation is implicated in IVD degeneration.MethodsClock gene dynamics in ex vivo IVD explants (from PER2:: luciferase (LUC) reporter mice) and human disc cells (transduced with lentivirus containing Per2::luc reporters) were monitored in real time by bioluminescence photon counting and imaging. Temporal gene expression changes were studied by RNAseq and quantitative reverse transcription (qRT)-PCR. IVD pathology was evaluated by histology in a mouse model with tissue-specific deletion of the core clock gene Bmal1.ResultsHere we show the existence of the circadian rhythm in mouse IVD tissue and human disc cells. This rhythm is dampened with ageing in mice and can be abolished by treatment with interleukin-1β but not tumour necrosis factor α. Time-series RNAseq revealed 607 genes with 24-hour patterns of expression representing several essential pathways in IVD physiology. Mice with conditional knockout of Bmal1 in their disc cells demonstrated age-related degeneration of IVDs.ConclusionsWe have established autonomous circadian clocks in mouse and human IVD cells which respond to age and cytokines, and control key pathways involved in the homeostasis of IVDs. Genetic disruption to the mouse IVD molecular clock predisposes to IVD degeneration. These results support the concept that disruptions to circadian rhythms may be a risk factor for degenerative IVD disease and low back pain.

scholarly journals Modeling circadian regulation of ovulation timing: age-related disruption of estrous cyclicity

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Takayuki Ohara ◽  
Takahiro J. Nakamura ◽  
Wataru Nakamura ◽  
Isao T. Tokuda
Keyword(s):  
Endocrine System ◽  
Aging Effect ◽  
Neuronal Firing ◽  
Circadian Clocks ◽  
Circadian Regulation ◽  
Estrous Cycles ◽  
Age Related ◽  
Estrous Cyclicity ◽  
Central Clock ◽  
Parameter Values

Abstract The circadian clocks within the hypothalamic–pituitary–gonadal axis control estrous cycles in female rodents. The suprachiasmatic nucleus (SCN), where the central clock is located, generates daily signals to trigger surge release of luteinizing hormone (LH), which in turn induces ovulation. It has been observed in aged rodents that output from the SCN such as neuronal firing activity is declined, and estrous cycles become irregular and finally stop. Circadian clock mutants display accelerated reproductive aging, suggesting the complicated interplay between the circadian system and the endocrine system. To investigate such circadian regulation of estrous cycles, we construct a mathematical model that describes dynamics of key hormones such as LH and of circadian clocks in the SCN and in the ovary, and simulate estrous cycles for various parameter values. Our simulation results demonstrate that reduction of the amplitude of the SCN signal, which is a symptom of aging, makes estrous cycles irregular. We also show that variation in the phase of the SCN signal and changes in the period of ovarian circadian clocks exacerbates the aging effect on estrous cyclicity. Our study suggests that misalignment between the SCN and ovarian circadian oscillations is one of the primary causes of the irregular estrous cycles.

Spindle shaped bodies in foveolar cones of the baboon retina

1989 ◽  
Vol 47 ◽  
pp. 960-961
Author(s):  
W. Krebs ◽  
I. Krebs
Keyword(s):  
Cross Sections ◽  
Inclusion Bodies ◽  
Photoreceptor Cells ◽  
Papio Anubis ◽  
Retinal Photoreceptor ◽  
Age Related ◽  
Cone Cells ◽  
Membrane Bound ◽  
Oriented Parallel ◽  
Shaped Inclusion

Various inclusion bodies occur in vertebrate retinal photoreceptor cells. Most of them are membrane bound and associated with phagocytosis or they are age related residual bodies. We found an additional inclusion body in foveal cone cells of the baboon (Papio anubis) retina.The eyes of a 15 year old baboon were fixed by immersion in cacodylate buffered glutaraldehyde (2%)/formaldehyde (2%) as described in detail elsewhere . Pieces of retina from various locations, including the fovea, were embedded in epoxy resin such that radial or tangential sections could be cut.Spindle shaped inclusion bodies were found in the cytoplasm of only foveal cones. They were abundant in the inner segments, close to the external limiting membrane (Fig. 1). But they also occurred in the outer fibers, the perikarya, and the inner fibers (Henle’s fibers) of the cone cells. The bodies were between 0.5 and 2 μm long. Their central diameter was 0.2 to 0. 3 μm. They always were oriented parallel to the long axis of the cone cells. In longitudinal sections (Figs. 2,3) they seemed to have a fibrous skeleton that, in cross sections, turned out to consist of plate-like (Fig.4) and tubular profiles (Fig. 5).

Autophagy and ageing: implications for age-related neurodegenerative diseases

2013 ◽  
Vol 55 ◽  
pp. 119-131 ◽  
Author(s):  
Bernadette Carroll ◽  
Graeme Hewitt ◽  
Viktor I. Korolchuk
Keyword(s):  
Neurodegenerative Diseases ◽  
Energy Availability ◽  
Future Studies ◽  
Intracellular Degradation ◽  
Age Related ◽  
Autophagy Induction ◽  
Social Importance ◽  
Cellular Dysfunction ◽  
Autophagy Activity ◽  
Intense Research

Autophagy is a process of lysosome-dependent intracellular degradation that participates in the liberation of resources including amino acids and energy to maintain homoeostasis. Autophagy is particularly important in stress conditions such as nutrient starvation and any perturbation in the ability of the cell to activate or regulate autophagy can lead to cellular dysfunction and disease. An area of intense research interest is the role and indeed the fate of autophagy during cellular and organismal ageing. Age-related disorders are associated with increased cellular stress and assault including DNA damage, reduced energy availability, protein aggregation and accumulation of damaged organelles. A reduction in autophagy activity has been observed in a number of ageing models and its up-regulation via pharmacological and genetic methods can alleviate age-related pathologies. In particular, autophagy induction can enhance clearance of toxic intracellular waste associated with neurodegenerative diseases and has been comprehensively demonstrated to improve lifespan in yeast, worms, flies, rodents and primates. The situation, however, has been complicated by the identification that autophagy up-regulation can also occur during ageing. Indeed, in certain situations, reduced autophagosome induction may actually provide benefits to ageing cells. Future studies will undoubtedly improve our understanding of exactly how the multiple signals that are integrated to control appropriate autophagy activity change during ageing, what affect this has on autophagy and to what extent autophagy contributes to age-associated pathologies. Identification of mechanisms that influence a healthy lifespan is of economic, medical and social importance in our ‘ageing’ world.

Oral and Oropharyngeal Sensory Function in Adults With Chronic Obstructive Pulmonary Disease

2020 ◽  
Vol 29 (2) ◽  
pp. 864-872
Author(s):  
Fernanda Borowsky da Rosa ◽  
Adriane Schmidt Pasqualoto ◽  
Catriona M. Steele ◽  
Renata Mancopes
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Oral Cavity ◽  
Pulmonary Disease ◽  
Thermal Sensation ◽  
Sensory Function ◽  
Control Group ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Age Related ◽  
Copd Patients

Introduction The oral cavity and pharynx have a rich sensory system composed of specialized receptors. The integrity of oropharyngeal sensation is thought to be fundamental for safe and efficient swallowing. Chronic obstructive pulmonary disease (COPD) patients are at risk for oropharyngeal sensory impairment due to frequent use of inhaled medications and comorbidities including gastroesophageal reflux disease. Objective This study aimed to describe and compare oral and oropharyngeal sensory function measured using noninstrumental clinical methods in adults with COPD and healthy controls. Method Participants included 27 adults (18 men, nine women) with a diagnosis of COPD and a mean age of 66.56 years ( SD = 8.68). The control group comprised 11 healthy adults (five men, six women) with a mean age of 60.09 years ( SD = 11.57). Spirometry measures confirmed reduced functional expiratory volumes (% predicted) in the COPD patients compared to the control participants. All participants completed a case history interview and underwent clinical evaluation of oral and oropharyngeal sensation by a speech-language pathologist. The sensory evaluation explored the detection of tactile and temperature stimuli delivered by cotton swab to six locations in the oral cavity and two in the oropharynx as well as identification of the taste of stimuli administered in 5-ml boluses to the mouth. Analyses explored the frequencies of accurate responses regarding stimulus location, temperature and taste between groups, and between age groups (“≤ 65 years” and “> 65 years”) within the COPD cohort. Results We found significantly higher frequencies of reported use of inhaled medications ( p < .001) and xerostomia ( p = .003) in the COPD cohort. Oral cavity thermal sensation ( p = .009) was reduced in the COPD participants, and a significant age-related decline in gustatory sensation was found in the COPD group ( p = .018). Conclusion This study found that most of the measures of oral and oropharyngeal sensation remained intact in the COPD group. Oral thermal sensation was impaired in individuals with COPD, and reduced gustatory sensation was observed in the older COPD participants. Possible links between these results and the use of inhaled medication by individuals with COPD are discussed.

Age-Related Differences in Processing Dynamic Information to Identify Vowel Quality

1992 ◽  
Vol 35 (4) ◽  
pp. 892-902 ◽  
Author(s):  
Robert Allen Fox ◽  
Lida G. Wall ◽  
Jeanne Gokcen
Keyword(s):  
Older Adults ◽  
Vowel Quality ◽  
Perceptual Cues ◽  
Dynamic Information ◽  
Process Dynamic ◽  
Center Condition ◽  
Age Related ◽  
Control Version ◽  
Older Subjects ◽  
Whole Word

This study examined age-related differences in the use of dynamic acoustic information (in the form of formant transitions) to identify vowel quality in CVCs. Two versions of 61 naturally produced, commonly occurring, monosyllabic English words were created: a control version (the unmodified whole word) and a silent-center version (in which approximately 62% of the medial vowel was replaced by silence). A group of normal-hearing young adults (19–25 years old) and older adults (61–75 years old) identified these tokens. The older subjects were found to be significantly worse than the younger subjects at identifying the medial vowel and the initial and final consonants in the silent-center condition. These results support the hypothesis of an age-related decrement in the ability to process dynamic perceptual cues in the perception of vowel quality.

Activity Engagement in Cognitive Aging: A Review of the Evidence

2013 ◽  
Vol 23 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Yvonne Rogalski ◽  
Muriel Quintana
Keyword(s):  
Older Adults ◽  
Cognitive Decline ◽  
Cognitive Aging ◽  
Social Activity ◽  
Current Evidence ◽  
Omega 3 ◽  
Neuroprotective Effects ◽  
Activity Engagement ◽  
Age Related ◽  
Age Related Cognitive Decline

The population of older adults is rapidly increasing, as is the number and type of products and interventions proposed to prevent or reduce the risk of age-related cognitive decline. Advocacy and prevention are part of the American Speech-Language-Hearing Association’s (ASHA’s) scope of practice documents, and speech-language pathologists must have basic awareness of the evidence contributing to healthy cognitive aging. In this article, we provide a brief overview outlining the evidence on activity engagement and its effects on cognition in older adults. We explore the current evidence around the activities of eating and drinking with a discussion on the potential benefits of omega-3 fatty acids, polyphenols, alcohol, and coffee. We investigate the evidence on the hypothesized neuroprotective effects of social activity, the evidence on computerized cognitive training, and the emerging behavioral and neuroimaging evidence on physical activity. We conclude that actively aging using a combination of several strategies may be our best line of defense against cognitive decline.

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