scholarly journals A Perspective on Accelerated Aging Caused by the Genetic Deficiency of the Metabolic Protein, OPA1

2021 ◽  
Vol 12 ◽  
Author(s):  
Irina Erchova ◽  
Shanshan Sun ◽  
Marcela Votruba
Keyword(s):  
Normal Development ◽  
Clinical Symptoms ◽  
Accelerated Aging ◽  
Cellular Level ◽  
Cellular Aging ◽  
Protective Mechanisms ◽  
Metabolic Protein ◽  
Cellular Defenses ◽  
Mutant Cells ◽  
Early Recruitment

Autosomal Dominant Optic Atrophy (ADOA) is an ophthalmological condition associated primarily with mutations in the OPA1 gene. It has variable onset, sometimes juvenile, but in other patients, the disease does not manifest until adult middle age despite the presence of a pathological mutation. Thus, individuals carrying mutations are considered healthy before the onset of clinical symptoms. Our research, nonetheless, indicates that on the cellular level pathology is evident from birth and mutant cells are different from controls. We argue that the adaptation and early recruitment of cytoprotective responses allows normal development and functioning but leads to an exhaustion of cellular reserves, leading to premature cellular aging, especially in neurons and skeletal muscle cells. The appearance of clinical symptoms, thus, indicates the overwhelming of natural cellular defenses and break-down of native protective mechanisms.

Psychological Stress and Cellular Aging

2017 ◽  
Author(s):  
Idan Shalev ◽  
Waylon J. Hastings
Keyword(s):  
Stress Response ◽  
Aging Process ◽  
Physiological Activity ◽  
Accelerated Aging ◽  
Cellular Level ◽  
Cellular Aging ◽  
Biological Stress ◽  
Short Term Exposure ◽  
Chronic Stressors ◽  
Different Types

Stress is a multistage process during which an organism perceives, interprets, and responds to threatening environmental stimuli. Physiological activity in the nervous, endocrine, and immune systems mediates the biological stress response. Although the stress response is adaptive in the short term, exposure to severe or chronic stressors dysregulates these biological systems, promoting maladaptive physiology and an accelerated aging phenotype, including aging on the cellular level. Two structures implicated in this process of stress and cellular aging are telomeres, whose length progressively decreases with age, and mitochondria, whose respiratory activity becomes increasingly inefficient with advanced age. Stress in its various forms is suggested to influence the maintenance and stability of these structures throughout life. Elucidating the interrelated connection between telomeres and mitochondria and how different types of stressors are influencing these structures to drive the aging process is of great interest. A better understanding of this subject can inform clinical treatments and intervention efforts to reduce (or even reverse) the damaging effects of stress on the aging process.

scholarly journals Telomere Shortening and Accelerated Aging in US Military Veterans

2021 ◽  
Vol 18 (4) ◽  
pp. 1743
Author(s):  
Jeffrey T. Howard ◽  
Jud C. Janak ◽  
Alexis R. Santos-Lozada ◽  
Sarah McEvilla ◽  
Stephanie D. Ansley ◽  
...  
Keyword(s):  
Telomere Length ◽  
Military Service ◽  
Accelerated Aging ◽  
Cellular Aging ◽  
Veterans Health ◽  
Cvd Risk ◽  
Base Pairs ◽  
Telomere Shortening ◽  
Race Ethnicity ◽  
Service Data

A growing body of literature on military personnel and veterans’ health suggests that prior military service may be associated with exposures that increase the risk of cardiovascular disease (CVD), which may differ by race/ethnicity. This study examined the hypothesis that differential telomere shortening, a measure of cellular aging, by race/ethnicity may explain prior findings of differential CVD risk in racial/ethnic groups with military service. Data from the first two continuous waves of the National Health and Nutrition Examination Survey (NHANES), administered from 1999–2002 were analyzed. Mean telomere length in base pairs was analyzed with multivariable adjusted linear regression with complex sample design, stratified by sex. The unadjusted mean telomere length was 225.8 base shorter for individuals with prior military service. The mean telomere length for men was 47.2 (95% CI: −92.9, −1.5; p < 0.05) base pairs shorter for men with military service after adjustment for demographic, socioeconomic, and behavioral variables, but did not differ significantly in women with and without prior military service. The interaction between military service and race/ethnicity was not significant for men or women. The results suggest that military service may contribute to accelerated aging as a result of health damaging exposures, such as combat, injury, and environmental contaminants, though other unmeasured confounders could also potentially explain the results.

A novel mitochondrial m.14430A>G (MT-ND6, p.W82R) variant causes complex I deficiency and mitochondrial Leigh syndrome

2020 ◽  
Vol 58 (11) ◽  
pp. 1809-1817
Author(s):  
Miaomiao Du ◽  
Xiujuan Wei ◽  
Pu Xu ◽  
Anran Xie ◽  
Xiyue Zhou ◽  
...  
Keyword(s):  
Mitochondrial Respiration ◽  
Complex I ◽  
Clinical Symptoms ◽  
Lactate Production ◽  
Mitochondrial Diseases ◽  
Leigh Syndrome ◽  
Extracellular Lactate ◽  
Next Generation Sequencing Ngs ◽  
Mutant Cells ◽  
Generation Sequencing

AbstractObjectivesLeigh syndrome (LS) is one of the most common mitochondrial diseases and has variable clinical symptoms. However, the genetic variant spectrum of this disease is incomplete.MethodsNext-generation sequencing (NGS) was used to identify the m.14430A > G (p.W82R) variant in a patient with LS. The pathogenesis of this novel complex I (CI) variant was verified by determining the mitochondrial respiration, assembly of CI, ATP, MMP and lactate production, and cell growth rate in cybrids with and without this variant.ResultsA novel m.14430A > G (p.W82R) variant in the NADH dehydrogenase 6 (ND6) gene was identified in the patient; the mutant loads of m.14430A > G (p.W82R) in the patient were much higher than those in his mother. Although the transmitochondrial cybrid-based study showed that mitochondrial CI assembly remains unaffected in cells with the m.14430G variant, control cells had significantly higher endogenous and CI-dependent mitochondrial respiration than mutant cells. Accordingly, mutant cells had a lower ATP, MMP and higher extracellular lactate production than control cells. Notably, mutant cells had impaired growth in a galactose-containing medium when compared to wild-type cells.ConclusionsA novel m.14430A > G (p.W82R) variant in the ND6 gene was identified from a patient suspected to have LS, and this variant impaired mitochondrial respiration by decreasing the activity of mitochondrial CI.

scholarly journals Double symmetrical aortic arch in a Czechoslovakian wolfdog – surgical treatment and health assessment four years after treatment: a case report

2017 ◽  
Vol 62 (No. 5) ◽  
pp. 279-284 ◽  
Author(s):  
P. Skrzypczak ◽  
A. Piatek ◽  
J. Biezynski ◽  
Z. Kielbowicz
Keyword(s):  
Aortic Arch ◽  
Normal Development ◽  
Clinical Symptoms ◽  
Good Condition ◽  
Health Assessment ◽  
Positive Outcome ◽  
Surrounding Tissue ◽  
Normal Position ◽  
Vascular Structures ◽  
Left And Right

The paper describes a double symmetrical aortic arch in a dog trapping the oesophagus. Thoracotomy was performed in the fourth inter-costal space under general, isoflurane-maintained, anaesthesia. Cutting of the arterial ligament failed to free the oesophagus. Dissection of further vascular structures revealed the left and right aortic arches to be of similar diameter. A vascular clamp was put on the left arch for 10 min, while the patient’s cardiovascular parameters were monitored. The lack of significant cardio-respiratory symptoms indicated the necessity of ligating and cutting the left aortic arch. Removal of additional tissue from the region of the cut on the left arch completely released the oesophagus which was continuously monitored by video-oesophagoscopy. The chest was closed according to a standard thoraco-surgical procedure. The cutting of the left aortic arch and the release of the surrounding tissue restored the normal position of the oesophagus. After surgery, the animal was returned to its owners in a very good condition. Control examination showed complete amelioration of clinical symptoms and subsequent normal development of the dog. Intra-operative clamping of the left aortic arch with simultaneous monitoring by oesophagoscopy ensured a positive outcome of the surgery of the intra-operatively diagnosed double aortic arch.

A wide-spectrum coordination model of schizophrenia

2003 ◽  
Vol 26 (1) ◽  
pp. 84-85
Author(s):  
Hendrik Pieter Barendregt
Keyword(s):  
Molecular Level ◽  
Clinical Symptoms ◽  
Wide Spectrum ◽  
Cellular Level ◽  
Cognitive Level ◽  
Levels Of Abstraction ◽  
Coordination Model ◽  
Target Article ◽  
Four Levels ◽  
Important Notion

AbstractThe target article presents a model for schizophrenia extending four levels of abstraction: molecules, cells, cognition, and syndrome. An important notion in the model is that of coordination, applicable to both the level of cells and of cognition. The molecular level provides an “implementation” of the coordination at the cellular level, which in turn underlies the coordination at the cognitive level, giving rise to the clinical symptoms.

scholarly journals Early-Life Adversity Accelerates Child and Adolescent Development

2019 ◽  
Vol 28 (3) ◽  
pp. 241-246 ◽  
Author(s):  
Jay Belsky
Keyword(s):  
Adolescent Development ◽  
Early Life ◽  
Brain Connectivity ◽  
Accelerated Aging ◽  
Premature Mortality ◽  
Well Being ◽  
Cellular Aging ◽  
Early Life Adversity ◽  
Trade Off ◽  
Developmental Experiences

Most developmental work regards adverse developmental experiences as forces that undermine well-being. Here, I present an alternative—or complementary—view, summarizing recent evidence on puberty, endocrinology, cellular aging, and brain connectivity that collectively reveals developmental acceleration in response to contextual adversity. Findings are cast in evolutionary-developmental terms, highlighting the trade-off between accelerated aging and (a) increased morbidity and (b) premature mortality.

scholarly journals Frontotemporal Dementia: A Clinical Review

2019 ◽  
Vol 39 (02) ◽  
pp. 251-263 ◽  
Author(s):  
Harri Sivasathiaseelan ◽  
Charles Marshall ◽  
Jennifer Agustus ◽  
Elia Benhamou ◽  
Rebecca Bond ◽  
...  
Keyword(s):  
Neural Network ◽  
Frontotemporal Dementia ◽  
Clinical Symptoms ◽  
Cellular Level ◽  
Diverse Group ◽  
Disease Modification ◽  
Selective Targeting ◽  
Young Onset Dementia ◽  
Presymptomatic Diagnosis ◽  
Frontotemporal Dementias

AbstractFrontotemporal dementias are a clinically, neuroanatomically, and pathologically diverse group of diseases that collectively constitute an important cause of young-onset dementia. Clinically, frontotemporal dementias characteristically strike capacities that define us as individuals, presenting broadly as disorders of social behavior or language. Neurobiologically, these diseases can be regarded as “molecular nexopathies,” a paradigm for selective targeting and destruction of brain networks by pathogenic proteins. Mutations in three major genes collectively account for a substantial proportion of behavioral presentations, with far-reaching implications for the lives of families but also potential opportunities for presymptomatic diagnosis and intervention. Predicting molecular pathology from clinical and radiological phenotypes remains challenging; however, certain patterns have been identified, and genetically mediated forms of frontotemporal dementia have spearheaded this enterprise. Here we present a clinical roadmap for diagnosis and assessment of the frontotemporal dementias, motivated by our emerging understanding of the mechanisms by which pathogenic protein effects at the cellular level translate to abnormal neural network physiology and ultimately, complex clinical symptoms. We conclude by outlining principles of management and prospects for disease modification.

scholarly journals Mood Disorders, Accelerated Aging, and Inflammation: Is the Link Hidden in Telomeres?

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 52 ◽  
Author(s):  
Alessio Squassina ◽  
Claudia Pisanu ◽  
Roberta Vanni
Keyword(s):  
Mood Disorders ◽  
Accelerated Aging ◽  
Cellular Level ◽  
Low Grade ◽  
Telomere Attrition ◽  
Excess Morbidity ◽  
Increased Risk ◽  
Bidirectional Association ◽  
Inflammatory State ◽  
Low Grade Inflammation

Mood disorders are associated with an increased risk of aging-related diseases, which greatly contribute to the excess morbidity and mortality observed in affected individuals. Clinical and molecular findings also suggest that mood disorders might be characterized by a permanent state of low-grade inflammation. At the cellular level, aging translates into telomeres shortening. Intriguingly, inflammation and telomere shortening show a bidirectional association: a pro-inflammatory state seems to contribute to aging and telomere dysfunction, and telomere attrition is able to induce low-grade inflammation. Several independent studies have reported shorter telomere length and increased levels of circulating inflammatory cytokines in mood disorders, suggesting a complex interplay between altered inflammatory–immune responses and telomere dynamics in the etiopathogenesis of these disorders. In this review, we critically discuss studies investigating the role of telomere attrition and inflammation in the pathogenesis and course of mood disorders, and in pharmacological treatments with psychotropic medications.

scholarly journals Cardiovascular deconditioning during long-term spaceflight through multiscale modeling

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Caterina Gallo ◽  
Luca Ridolfi ◽  
Stefania Scarsoglio
Keyword(s):  
Cardiovascular Response ◽  
Accelerated Aging ◽  
Multiscale Model ◽  
Cellular Level ◽  
Physical Capability ◽  
Cardiovascular Deconditioning ◽  
Partial Gravity ◽  
Volume Shift ◽  
Blood Volume Shift

Abstract Human spaceflight has been fascinating man for centuries, representing the intangible need to explore the unknown, challenge new frontiers, advance technology, and push scientific boundaries further. A key area of importance is cardiovascular deconditioning, that is, the collection of hemodynamic changes—from blood volume shift and reduction to altered cardiac function—induced by sustained presence in microgravity. A thorough grasp of the 0G adjustment point per se is important from a physiological viewpoint and fundamental for astronauts’ safety and physical capability on long spaceflights. However, hemodynamic details of cardiovascular deconditioning are incomplete, inconsistent, and poorly measured to date; thus a computational approach can be quite valuable. We present a validated 1D–0D multiscale model to study the cardiovascular response to long-term 0G spaceflight in comparison to the 1G supine reference condition. Cardiac work, oxygen consumption, and contractility indexes, as well as central mean and pulse pressures were reduced, augmenting the cardiac deconditioning scenario. Exercise tolerance of a spaceflight traveler was found to be comparable to an untrained person with a sedentary lifestyle. At the capillary–venous level significant waveform alterations were observed which can modify the regular perfusion and average nutrient supply at the cellular level. The present study suggests special attention should be paid to future long spaceflights which demand prompt physical capacity at the time of restoration of partial gravity (e.g., Moon/Mars landing). Since spaceflight deconditioning has features similar to accelerated aging understanding deconditioning mechanisms in microgravity are also relevant to the understanding of aging physiology on the Earth.

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