scholarly journals FOXO3, Telomere Dynamics, and Healthy Brain Aging: A COBRE Study

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 368-368
Author(s):  
Bradley Willcox ◽  
Kamal Masaki ◽  
Richard Allsopp ◽  
Kalpana Kallianpur
Keyword(s):  
Brain Aging ◽  
Peripheral Blood Leukocyte ◽  
Telomerase Activity ◽  
Cellular Aging ◽  
Human Longevity ◽  
Telomere Shortening ◽  
Wide Range ◽  
Brain Structure And Function ◽  
Blood Leukocyte ◽  
And Function

Abstract Human longevity is linked to genetic, cellular, and other complex biological and psychosocial traits. Aging is typically accompanied by gradual brain atrophy and cognitive decline, but the mechanisms are unclear. Cellular aging, characterized by telomere shortening and altered telomerase activity, is related to mortality and brain aging. Decelerated brain aging is associated with greater peripheral blood leukocyte telomere length (LTL) and, we hypothesize, may be linked to FOXO3 genotype. We will use MRI to assess brain structure and function cross-sectionally in 100 Kuakini Honolulu Heart Program Offspring. Atrophy and disrupted functional connectivity, markers of brain aging, will be examined in relation to FOXO3 and LTL. Associations between brain structural and functional differences, FOXO3 genotype and LTL will be investigated over a wide range of ages, controlling for other biological and psychosocial factors. Results may provide insight into mechanisms influencing the rate of brain aging, and may eventually extend human healthspan.

scholarly journals Accelerated brain aging and cerebral blood flow reduction in persons with HIV

2021 ◽  
Author(s):  
Kalen J Petersen ◽  
Nicholas Metcalf ◽  
Sarah Cooley ◽  
Dimitre Tomov ◽  
Florin Vaida ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Brain Aging ◽  
Learning Algorithm ◽  
Psychomotor Speed ◽  
Deep Learning Algorithm ◽  
Blood Flow Reduction ◽  
Brain Structure And Function ◽  
N 93 ◽  
And Function

Abstract Background Persons with HIV (PWH) are characterized by altered brain structure and function. As they attain normal lifespans, it has become crucial to understand potential interactions between HIV and aging. However, it remains unclear how brain aging varies with viral load (VL). Methods In this study, we compare MRI biomarkers amongst PWH with undetectable VL (UVL; ≤50 genomic copies/ml; n=230), PWH with detectable VL (DVL; >50 copies/ml; n=93), and HIV uninfected (HIV-) controls (n=206). To quantify gray matter cerebral blood flow (CBF), we utilized arterial spin labeling. To measure structural aging, we used a publicly available deep learning algorithm to estimate brain age from T1-weighted MRI. Cognitive performance was measured using a neuropsychological battery covering five domains. Results Associations between age and CBF varied with VL. Older PWH with DVL had reduced CBF vs. PWH with UVL (p=0.02). Structurally predicted brain aging was accelerated in PWH vs. HIV- controls regardless of VL (p<0.001). Overall, PWH had impaired learning, executive function, psychomotor speed, and language compared to HIV- controls. Structural brain aging was associated with reduced psychomotor speed (p<0.001). Conclusions Brain aging in HIV is multifaceted. CBF depends on age and current VL, and is improved by medication adherence. By contrast, structural aging is an indicator of cognitive function and reflects serostatus rather than current VL.

Hormone-brain-aging relationships, broadly reactive with imidazole-containing dipeptides: targeting of telomere attrition as an aging biomarker and dynamic telomerase activity flirting

2015 ◽  
Vol 26 (2) ◽  
Author(s):  
Mark A. Babizhayev ◽  
Khava S. Vishnyakova ◽  
Yegor E. Yegorov
Keyword(s):  
Healthy Aging ◽  
Brain Aging ◽  
The United States ◽  
Telomerase Activity ◽  
Therapeutic Drug ◽  
Physiological Control ◽  
Telomere Shortening ◽  
Therapeutic Concept ◽  
Telomere Attrition ◽  
Age Related

AbstractIt has been documented that telomere-associated cellular senescence may contribute to certain age-related disorders, and telomere length (TL) may be an informative biomarker of healthy aging. Hormone-brain-aging behavior-modulated telomere dynamics and changes in telomerase activity are consistent elements of cellular alterations associated with changes in proliferative state, and these processes are consequently considered as the new therapeutic drug targets for physiological control with advanced drug delivery and nutritional formulations. We raise and support a therapeutic concept of using nonhydrolyzed forms of naturally occurring neuron-specific imidazole dipeptide-based compounds carnosine and carcinine, making it clinically possible that slowing down the rate of telomere shortening could slow down the human aging process in specific tissues where proliferative senescence is known to occur, with the demonstrated evidence of telomere shortening that appeared to be a hallmark of oxidative stress and disease. Carnosine released from skeletal muscle during exercise may be transported into the hypothalamic tuberomammillary nucleus (TMN) histamine neurons and hydrolyzed. The resulting L-histidine may subsequently be converted into histamine, which could be responsible for the effects of carnosine on neurotransmission and hormone-like antiaging physiological function. The preliminary longitudinal studies of elderly individuals suggest that longer telomeres are associated with better survival, and an advanced oral nutritional support with nonhydrolyzed carnosine (or carcinine and patented compositions thereof) is a useful therapeutic tool for a critical TL maintenance that may fundamentally be applied in the treatment of age-related sight-threatening eye disorders, prolonged life expectancy, increased survival and chronological age of an organism in health control, smoking behavior, and disease.  “Our pleasures were simple—they included survival.”   —Dwight D. Eisenhower, 34th President of the United States, 1953–1961

scholarly journals Artificial Neural Networks in Agriculture

Agriculture ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 497
Author(s):  
Sebastian Kujawa ◽  
Gniewko Niedbała
Keyword(s):  
Artificial Intelligence ◽  
Machine Learning ◽  
Neural Networks ◽  
Artificial Neural Networks ◽  
Transport Processes ◽  
High Quality Research ◽  
Wide Range ◽  
Brain Structure And Function ◽  
Artificial Neural ◽  
And Function

Artificial neural networks are one of the most important elements of machine learning and artificial intelligence. They are inspired by the human brain structure and function as if they are based on interconnected nodes in which simple processing operations take place. The spectrum of neural networks application is very wide, and it also includes agriculture. Artificial neural networks are increasingly used by food producers at every stage of agricultural production and in efficient farm management. Examples of their applications include: forecasting of production effects in agriculture on the basis of a wide range of independent variables, verification of diseases and pests, intelligent weed control, and classification of the quality of harvested crops. Artificial intelligence methods support decision-making systems in agriculture, help optimize storage and transport processes, and make it possible to predict the costs incurred depending on the chosen direction of management. The inclusion of machine learning methods in the “life cycle of a farm” requires handling large amounts of data collected during the entire growing season and having the appropriate software. Currently, the visible development of precision farming and digital agriculture is causing more and more farms to turn to tools based on artificial intelligence. The purpose of this Special Issue was to publish high-quality research and review papers that cover the application of various types of artificial neural networks in solving relevant tasks and problems of widely defined agriculture.

scholarly journals The Effect of Ethanol on Telomere Dynamics and Regulation in Human Cells

Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 169 ◽  
Author(s):  
Tomer Harpaz ◽  
Heba Abumock ◽  
Einat Beery ◽  
Yonatan Edel ◽  
Meir Lahav ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Methylation Status ◽  
Telomerase Activity ◽  
Cellular Aging ◽  
Human Foreskin Fibroblast ◽  
Telomere Shortening ◽  
Social Drinking ◽  
Carcinogenic Potential ◽  
Human Hepatocellular Carcinoma Cells ◽  
In Cells

Telomeres (TLs) protect chromosome ends from chromosomal fusion and degradation, thus conferring genomic stability, and play crucial roles in cellular aging and disease. Recent studies have found a correlation between environmental, physiological and even mental stresses on TL dynamics in humans. However, the causal relationship between stress and TL length and the molecular mechanisms underlying that relationship are far from being understood. This study describes the effect of moderate concentrations of ethanol, equivalent to social drinking, on human TL dynamics and partially elucidates the mechanism mediating this effect. The exposure of Immortalized human foreskin fibroblast, primary human foreskin fibroblast and human hepatocellular carcinoma cells to 25 mM ethanol for one week moderately shortened telomeres in all cells. Similar TL shortening was obtained following cells’ exposure to 25 µM acetaldehyde (AcH) and to a much lower extent after exposure to 4-methylpyrazolean, an inhibitor of alcoholdehydrogenase, suggesting that AcH plays a key role in ethanol-dependent telomere shortening. Telomerase activity was not involved in this effect. TRF2 and several TRF2 binding proteins increased their binding to TLs after ethanol treatment, implying their involvement in this effect. The methylation status of several sub-telomeric regions increased in response to EtOH exposure. Gene expression profiling showed distinct patterns in cells treated with EtOH and in cells recovered from EtOH. In addition to cellular ageing, the described telomere shortening may contribute to the carcinogenic potential of acute alcohol consumption; both are associated with the shortening of TLs and provide new insights regarding the moderate consumption of alcohol referred to as “social drinking.”

scholarly journals Genetics of brain age suggest an overlap with common brain disorders

2018 ◽  
Author(s):  
Tobias Kaufmann ◽  
Dennis van der Meer ◽  
Nhat Trung Doan ◽  
Emanuel Schwarz ◽  
Martina J. Lund ◽  
...  
Keyword(s):  
Healthy Adult ◽  
Brain Aging ◽  
Brain Disorders ◽  
Regional Patterns ◽  
Age Gap ◽  
Brain Structure And Function ◽  
Common Risk Factors ◽  
Genetic And Environmental Factors ◽  
And Function ◽  
Brain Age

Numerous genetic and environmental factors contribute to psychiatric disorders and other brain disorders. Common risk factors likely converge on biological pathways regulating the optimization of brain structure and function across the lifespan. Here, using structural magnetic resonance imaging and machine learning, we estimated the gap between brain age and chronological age in 36,891 individuals aged 3 to 96 years, including individuals with different brain disorders. We show that several disorders are associated with accentuated brain aging, with strongest effects in schizophrenia, multiple sclerosis and dementia, and document differential regional patterns of brain age gaps between disorders. In 16,269 healthy adult individuals, we show that brain age gap is heritable with a polygenic architecture overlapping those observed in common brain disorders. Our results identify brain age gap as a genetically modulated trait that offers a window into shared and distinct mechanisms in different brain disorders.

scholarly journals Astaxanthin as a Putative Geroprotector: Molecular Basis and Focus on Brain Aging

Marine Drugs ◽  
2020 ◽  
Vol 18 (7) ◽  
pp. 351 ◽  
Author(s):  
Vincenzo Sorrenti ◽  
Sergio Davinelli ◽  
Giovanni Scapagnini ◽  
Bradley J. Willcox ◽  
Richard C. Allsopp ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cell Fate ◽  
Brain Aging ◽  
Membrane Surface ◽  
Experimental Models ◽  
Cellular Level ◽  
Human Longevity ◽  
Mitochondrial Functions ◽  
And Function ◽  
The Brain

In recent years, the scientific interest in natural compounds with geroprotective activities has grown exponentially. Among the various naturally derived molecules, astaxanthin (ASX) represents a highly promising candidate geroprotector. By virtue of the central polyene chain, ASX acts as a scavenger of free radicals in the internal membrane layer and simultaneously controls oxidation on the membrane surface. Moreover, several studies have highlighted ASX’s ability to modulate numerous biological mechanisms at the cellular level, including the modulation of transcription factors and genes directly linked to longevity-related pathways. One of the main relevant evolutionarily-conserved transcription factors modulated by astaxanthin is the forkhead box O3 gene (FOXO3), which has been recognized as a critical controller of cell fate and function. Moreover, FOXO3 is one of only two genes shown to robustly affect human longevity. Due to its tropism in the brain, ASX has recently been studied as a putative neuroprotective molecule capable of delaying or preventing brain aging in different experimental models of brain damage or neurodegenerative diseases. Astaxanthin has been observed to slow down brain aging by increasing brain-derived neurotrophic factor (BDNF) levels in the brain, attenuating oxidative damage to lipids, protein, and DNA and protecting mitochondrial functions. Emerging data now suggest that ASX can modulate Nrf2, FOXO3, Sirt1, and Klotho proteins that are linked to longevity. Together, these mechanisms provide support for a role of ASX as a potential geroneuroprotector.

scholarly journals What We Talk About When We Talk About Binge Drinking: Towards an Integrated Conceptualization and Evaluation

2020 ◽  
Vol 55 (5) ◽  
pp. 468-479 ◽  
Author(s):  
Pierre Maurage ◽  
Séverine Lannoy ◽  
Jessica Mange ◽  
Delphine Grynberg ◽  
Hélène Beaunieux ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Binge Drinking ◽  
Psychological Symptoms ◽  
Consumption Pattern ◽  
Main Concern ◽  
Research Perspectives ◽  
Evaluation Protocol ◽  
Wide Range ◽  
Brain Structure And Function ◽  
And Function

Abstract Rationale Binge drinking (BD), characterized by recurring alternations between intense intoxication episodes and abstinence periods, is the most frequent alcohol consumption pattern in youth and is growing in prevalence among older adults. Many studies have underlined the specific harmful impact of this habit by showing impaired abilities in a wide range of cognitive functions among binge drinkers, as well as modifications of brain structure and function. Aims Several controversies and inconsistencies currently hamper the harmonious development of the field and the recognition of BD as a specific alcohol consumption pattern. The main concern is the absence of consensual BD conceptualization, leading to variability in experimental group selection and alcohol consumption evaluation. The present paper aims at overcoming this key issue through a two-step approach. Methods and conclusions First, a literature review allows proposing an integrated BD conceptualization, distinguishing it from other subclinical alcohol consumption patterns. Six specific characteristics of BD are identified, namely, (1) the presence of physiological symptoms related to BD episodes, (2) the presence of psychological symptoms related to BD episodes, (3) the ratio of BD episodes compared to all alcohol drinking occasions, (4) the frequency of BD episodes, (5) the consumption speed and (6) the alternation between BD episodes and soberness periods. Second, capitalizing on this conceptual clarification, we propose an evaluation protocol jointly measuring these six BD characteristics. Finally, several research perspectives are presented to refine the proposed conceptualization.

scholarly journals Age-Related Trajectories of Brain Structure–Function Coupling in Female Roller Derby Athletes

2021 ◽  
Vol 12 (1) ◽  
pp. 22
Author(s):  
Derek C. Monroe ◽  
Samantha L. DuBois ◽  
Christopher K. Rhea ◽  
Donna M. Duffy
Keyword(s):  
Brain Structure ◽  
Sport Participation ◽  
Female Athletes ◽  
Brain Aging ◽  
Roller Derby ◽  
Neurodegenerative Process ◽  
Frontoparietal Network ◽  
Age Related ◽  
Brain Structure And Function ◽  
And Function

Contact and collision sports are believed to accelerate brain aging. Postmortem studies of the human brain have implicated tau deposition in and around the perivascular space as a biomarker of an as yet poorly understood neurodegenerative process. Relatively little is known about the effects that collision sport participation has on the age-related trajectories of macroscale brain structure and function, particularly in female athletes. Diffusion MRI and resting-state functional MRI were obtained from female collision sport athletes (n = 19 roller derby (RD) players; 23–45 years old) and female control participants (n = 14; 20–49 years old) to quantify structural coupling (SC) and decoupling (SD). The novel and interesting finding is that RD athletes, but not controls, exhibited increasing SC with age in two association networks: the frontoparietal network, important for cognitive control, and default-mode network, a task-negative network (permuted p = 0.0006). Age-related increases in SC were also observed in sensorimotor networks (RD, controls) and age-related increases in SD were observed in association networks (controls) (permuted p ≤ 0.0001). These distinct patterns suggest that competing in RD results in compressed neuronal timescales in critical networks as a function of age and encourages the broader study of female athlete brains across the lifespan.

Sign in / Sign up

Export Citation Format

Share Document