scholarly journals Kuakini HHP Center for Translational Research on Aging: Aims and Preliminary Findings

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 367-367
Author(s):  
Bradley Willcox ◽  
Richard Allsopp ◽  
Peter Martin
Keyword(s):  
Translational Research ◽  
Medical Center ◽  
Telomerase Activity ◽  
Attrition Rate ◽  
Healthy Human ◽  
Aging Research ◽  
Attrition Rates ◽  
Telomere Attrition ◽  
Human Lifespan ◽  
The Impact

Abstract Kuakini Medical Center (Kuakini) is creating an interdisciplinary Hawai’i-based Center for translational research on aging. This Center will build upon Kuakini’s five-decades of NIH-funded research, its 420,000-specimen biorepository, and existing strengths in aging research, notably, the 56-year ongoing Kuakini Honolulu Heart Program cohort study (Kuakini HHP), Kuakini Honolulu-Asia Aging Study (Kuakini HAAS), and Kuakini HHP Offspring Study. The overall goal is to find practical means to enhance healthy human lifespan (healthspan). Four research project leaders (RPLs) have been selected from various disciplines for mentorship in translational aging research. The first RPL presentation will introduce a novel mouse model, enabling controlled expression of the pro-longevity gene FoxO3, and assess the impact on lifespan and healthspan phenotypes in mice. These phenotypes will be compared to similar phenotypes in humans with/without the FOXO3 longevity genotype. The second RPL presentation will assess the relation between leukocyte telomere attrition rates (from banked blood collected at three time points over 20-plus years) in older Kuakini HHP men with/without the FOXO3 longevity genotype. The third RPL presentation will assess whether FOXO3 genotype, peripheral leukocyte telomere dynamics (attrition rate, telomerase activity) and inflammatory cytokines mediate the human brain integrity and function with age. This project will utilize structural and functional MRI data from male and female Kuakini HHP Offspring Study participants. The fourth RPL presentation will assess whether APOE e2, e4, and FOXO3 longevity-associated alleles impact 34-year incidence of intracerebral hemorrhage. We will summarize the findings, address the healthspan implications and provide future directions. Supported by NIH 5P20GM125526.

Telomerase-Positive Somatic Tissues of Honeybee Queens (Apis mellifera) Display No DNA Replication

2021 ◽  
pp. 1-6
Author(s):  
Justina Koubová ◽  
Radmila Čapková Frydrychová
Keyword(s):  
Apis Mellifera ◽  
Dna Replication ◽  
Cell Types ◽  
Telomerase Activity ◽  
Protective Mechanism ◽  
Aging Research ◽  
Telomere Attrition ◽  
Eusocial Insects ◽  
Somatic Tissues ◽  
Telomere Biology

Telomere biology is closely linked to the process of aging. The restoration of telomere length by maintaining telome­rase activity in certain cell types of human adults allows for the proliferative capacity of the cells and preserves the regeneration potential of the tissue. The absence of telome­rase, that leads to telomere attrition and irreversible cell cycle arrest in most somatic cells, acts as a protective mechanism against uncontrolled cancer growth. Nevertheless, there have been numerous studies indicating noncanonical functions of telomerase besides those involved in telomere lengthening. Eusocial insects serve as a great system for aging research. This is because eusocial reproductives, such as queens and kings, have a significantly extended lifespan compared to nonreproductive individuals of the same species. We report that the somatic tissues of honeybee queens (<i>Apis mellifera</i>) are associated with upregulated telomerase activity; however, this upregulation does not fully correlate with the rate of DNA replication in the tissues. This indicates a noncanonical role of telomerase in the somatic tissues of honeybee queens.

scholarly journals Telomere length: how the length makes a difference

2020 ◽  
Vol 47 (9) ◽  
pp. 7181-7188 ◽  
Author(s):  
M. Lulkiewicz ◽  
J. Bajsert ◽  
P. Kopczynski ◽  
W. Barczak ◽  
B. Rubis
Keyword(s):  
Telomere Length ◽  
Meta Analysis ◽  
Telomerase Activity ◽  
Human Cells ◽  
Attrition Rate ◽  
Severe Damage ◽  
Telomere Attrition ◽  
Adult Men ◽  
Cell Life ◽  
Real Value

Abstract Telomerase is perceived as an immortality enzyme that might provide longevity to cells and whole organisms. Importantly, it is generally inactive in most somatic cells of healthy, adult men. Consequently, its substrates, i.e. telomeres, get shorter in most human cells with time. Noteworthy, cell life limitation due to telomere attrition during cell divisions, may not be as bad as it looks since longer cell life means longer exposition to harmful factors. Consequently, telomere length (attrition rate) becomes a factor that is responsible for inducing the signaling that leads to the elimination of cells that lived long enough to acquire severe damage. It seems that telomere length that depends on many different factors (including telomerase activity but also genetic factors, a hormonal profile that reflects sex, etc.) might become a useful marker of aging and exposition to stress. Thus in the current paper, we review the factors that affect telomere length in human cells focusing on sex that all together with different environmental and hormonal regulations as well as parental aspect affect telomere attrition rate. We also raise some limitations in the assessment of telomere length that hinders a trustworthy meta-analysis that might lead to acknowledgment of the real value of this parameter.

scholarly journals Resveratrol: A Sirtuin Activator and The Fountain of Youth

2015 ◽  
Vol 7 (1) ◽  
pp. 1 ◽  
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya
Keyword(s):  
Caloric Restriction ◽  
Healthy Aging ◽  
Myocardial Infarct ◽  
Functional Decline ◽  
Steady Increase ◽  
Healthy Human ◽  
Aging Research ◽  
Human Lifespan ◽  
Age Related ◽  
Fountain Of Youth

BACKGROUND: An organism’s lifespan is inevitably accompanied by the aging process, which involves functional decline, a steady increase of a plethora of chronic diseases, and ultimately death. Thus, it has been an ongoing dream of mankind to improve healthspan and extend life.CONTENT: There are only a few proposed aging interventions: caloric restriction, exercise, and the use of low-molecular-weight compounds, including spermidine, metformin, resveratrol, and rapamycin. Resveratrol, a constituent of red wine, has long been suspected to have cardioprotective effects. Interest in this compound has been renewed in recent years, first from its identification as a chemopreventive agent for skin cancer, and subsequently from reports that it activates sirtuin deacetylases and extends the lifespans of lower organisms. Resveratrol have been shown to prevent and reduce the severity of age-related diseases such as atherosclerosis, stroke, myocardial infarct, diabetes, neurodegenerative diseases, osteoarthritis, tumors and metabolic syndrome, along with their ability to extend lifespan.SUMMARY: The purpose of aging research is the identification of interventions that may avoid or ameliorate the ravages of time. In other words, the quest is for healthy aging, where improved longevity is coupled to a corresponding healthspan extension. It is only by extending the healthy human lifespan that we will truly meet the premise of the Roman poet Cicero: “No one is so old as to think that he may not live a year.”KEYWORDS: aging, caloric restriction, mimetic, healthspan, sirtuin activator

scholarly journals Kuakini HHP Center for Translational Research on Aging: An Introduction

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 367-368
Author(s):  
Kamal Masaki ◽  
Tim Donlon ◽  
Donald Willcox ◽  
Brian Morris ◽  
Richard Allsopp ◽  
...  
Keyword(s):  
Translational Research ◽  
Biomedical Research ◽  
State Of The Art ◽  
Medical Center ◽  
Research Strategy ◽  
Aging Research ◽  
World Class ◽  
Research Excellence ◽  
Clinical And Translational Research ◽  
Future Plans

Abstract sKuakini Medical Center (Kuakini) is establishing an interdisciplinary Hawai’i-based Center of Biomedical Research Excellence (COBRE) for clinical and translational research on aging. - Specific Aim 1: Create a world class, innovative, interdisciplinary Center for Translational Research on Aging by building on the existing rare and valuable Kuakini Honolulu Heart Program (Kuakini HHP) and its related studies and research infrastructure. - Specific Aim 2: Advance the genomic, biological and clinical science of aging, and enhance the world class character of our Center, by enlisting accomplished senior scientists to mentor promising Hawaii-based new investigators in interdisciplinary aging research and career development. - Specific Aim 3: Elevate the capacity of our Center by: i) creating a state-of-the-art Clinical and Translational Core, and ii) collaborating with other Centers of Biomedical Research Excellence. This presentation will briefly introduce the Center and discuss its aims, research strategy, and future plans.

Abstract 1411: Doxorubicin Triggers Replicative Senescence and Death of Cardiac Progenitor Cells

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Elena Piegari ◽  
Antonella De Angelis ◽  
Toru Hosoda ◽  
Donato Cappetta ◽  
Laura Marino ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dna Damage ◽  
Manganese Superoxide Dismutase ◽  
Replicative Senescence ◽  
Telomerase Activity ◽  
Telomere Attrition ◽  
Manganese Superoxide ◽  
Severe Reduction ◽  
Transcription Factor P53 ◽  
The Impact

Doxorubicin (DOXO) is a very effective drug for the treatment of neoplastic diseases. However, DOXO causes a cardiomyopathy that leads to congestive heart failure. To test whether DOXO affects the cardiac progenitor cell (CPC) compartment, CPCs were exposed to increasing doses of the anthracycline for 12, 24 and 48 hours. At 0.1 μ M, DOXO did not alter CPC survival. However, 0.5 and 1 μ M DOXO reduced progressively and dramatically CPC viability. Apoptosis measured by TdT assay, DNA laddering and caspase-3 activity increased markedly with time peaking at 48 hours. The impact of DOXO on CPC growth was determined by BrdU and phospho-H3 labeling. The percentage of BrdU-positive CPCs and the mitotic index decreased with increasing doses of DOXO and time. The expression of the molecular regulators of G1 and G1\S transition, cyclin D1 and cdk4, decreased progressively with increasing concentration of DOXO and time, and these changes were coupled with a severe reduction in phospho-Rb in CPCs. Also, DOXO resulted in a transient increase of the cell cycle inhibitor p21 Cip and a persistent increase in p16 INK4a in CPCs. To determine whether the generation of reactive oxygen species (ROS) was responsible for DNA damage in CPCs, the presence of 8-OH-deoxyguanosine (8-OHdG) was measured. DOXO treatment strikingly increased the fraction of CPCs positive for 8-OHdG. Moreover, the expression of the antioxidant enzymes manganese superoxide dismutase and catalase failed to increase and counteract ROS-mediated DNA damage. Severe telomeric shortening occurred in CPCs exposed to DOXO. Telomere attrition was also favored by a significant decrease in telomerase activity in DOXO-treated CPCs. Dysfunctional telomeres trigger a DNA damage response in which the major determinant is the expression of p53. Both the transcription factor p53 and its target gene p21 Cip1 were upregulated in DOXO-treated CPCs. These molecular adaptations of CPCs increased with the dose and time of exposure to the anthracycline. In conclusion, these observations support the notion that DOXO-induced heart failure is a stem cell cardiomyopathy.

The Impact of Translational Research in Breast Cancer Care: Can we Improve the Therapeutic Scenario?

2018 ◽  
Vol 18 (6) ◽  
pp. 832-836
Author(s):  
Giuseppe Buono ◽  
Francesco Schettini ◽  
Francesco Perri ◽  
Grazia Arpino ◽  
Roberto Bianco ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Translational Research ◽  
Cell Biology ◽  
Cancer Biology ◽  
Hormone Receptors ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Molecular Heterogeneity ◽  
Therapeutic Implications ◽  
The Impact

Traditionally, breast cancer (BC) is divided into different subtypes defined by immunohistochemistry (IHC) according to the expression of hormone receptors and overexpression/amplification of human epidermal growth factor receptor 2 (HER2), with crucial therapeutic implications. In the last few years, the definition of different BC molecular subgroups within the IHC-defined subtypes and the identification of the important role that molecular heterogeneity can play in tumor progression and treatment resistance have inspired the search for personalized therapeutic approaches. In this scenario, translational research represents a key strategy to apply knowledge from cancer biology to the clinical setting, through the study of all the tumors “omics”, including genomics, transcriptomics, proteomics, epigenomics, and metabolomics. Importantly, the introduction of new high-throughput technologies, such as next generation sequencing (NGS) for the study of cancer genome and transcriptome, greatly amplifies the potential and the applications of translational research in the oncology field. Moreover, the introduction of new experimental approaches, such as liquid biopsy, as well as new-concept clinical trials, such as biomarker-driven adaptive studies, may represent a turning point for BC translational research. </P><P> It is likely that translational research will have in the near future a significant impact on BC care, especially by giving us the possibility to dissect the complexity of tumor cell biology and develop new personalized treatment strategies.

The Impact of Environmental Stress on Cognitive Performance: A Systematic Review

2019 ◽  
Vol 61 (8) ◽  
pp. 1205-1246 ◽  
Author(s):  
Kristy Martin ◽  
Emily McLeod ◽  
Julien Périard ◽  
Ben Rattray ◽  
Richard Keegan ◽  
...  
Keyword(s):  
Systematic Review ◽  
Environmental Stress ◽  
Task Performance ◽  
Sea Level ◽  
Cognitive Performance ◽  
Cognitive Task ◽  
Individual Characteristics ◽  
Eligibility Criteria ◽  
Healthy Human ◽  
The Impact

Objective: In this review, we detail the impact of environmental stress on cognitive and military task performance and highlight any individual characteristics or interventions which may mitigate any negative effect. Background: Military personnel are often deployed in regions markedly different from their own, experiencing hot days, cold nights, and trips both above and below sea level. In spite of these stressors, high-level cognitive and operational performance must be maintained. Method: A systematic review of the electronic databases Medline (PubMed), EMBASE (Scopus), PsycINFO, and Web of Science was conducted from inception up to September 2018. Eligibility criteria included a healthy human cohort, an outcome of cognition or military task performance and assessment of an environmental condition. Results: The search returned 113,850 records, of which 124 were included in the systematic review. Thirty-one studies examined the impact of heat stress on cognition; 20 of cold stress; 59 of altitude exposure; and 18 of being below sea level. Conclusion: The severity and duration of exposure to the environmental stressor affects the degree to which cognitive performance can be impaired, as does the complexity of the cognitive task and the skill or familiarity of the individual performing the task. Application: Strategies to improve cognitive performance in extreme environmental conditions should focus on reducing the magnitude of the physiological and perceptual disturbance caused by the stressor. Strategies may include acclimatization and habituation, being well skilled on the task, and reducing sensations of thermal stress with approaches such as head and neck cooling.

scholarly journals The Fellow’s Perspective: The Impact of the COVID-19 Pandemic on Fellowship Training and Job Appointment

2021 ◽  
pp. 000313482110241
Author(s):  
Adam Truong ◽  
Farin Amersi ◽  
Van Chau ◽  
Taryne Imai
Keyword(s):  
Clinical Training ◽  
Medical Center ◽  
Fellowship Training ◽  
Surgical Specialty ◽  
Job Interview ◽  
Educational Structure ◽  
Global Pandemic ◽  
Procedural Volume ◽  
Interview Format ◽  
The Impact

Background Fellows have been uniquely affected by the widespread changes in educational structure, mandatory limitations in elective procedural volume, and hiring freezes during the COVID-19 global pandemic. Study Design A voluntary and anonymous survey was distributed to all Graduate Medical Education fellows at a tertiary medical center querying perspectives on clinical and didactic training and job placement. Results A total of 47 of 121 fellows (39%) completed the survey. The majority were in a medical (43%) or surgical specialty (34%) followed by critical care (13%) and procedure-based (11%) fellowships. Approximately 59% of surveyed fellows felt their programs were providing a virtual curriculum that would train them just as well as the in-person curriculum. Twenty-eight (60%) fellows were in their final or only year of training. Of the 25 fellows who were seeking employment, 52% have experienced difficulty in finding a job due to hiring freezes and 40% have encountered challenges with job interview cancellations and changes to virtual interview formats. Conclusion Almost half of surveyed fellows reported an educational deterioration due to COVID-19 and graduating fellows seeking employment felt hindered by both the virtual interview format and widespread hiring freeze. Fellows are both unique and vulnerable as they balance the solidification of clinical training with securing employment during these tumultuous and unprecedented times.

scholarly journals Alcohol Hand Rub Significantly Reduces Overall Bacterial Bioburden on Stethoscopes in a Real-World Clinical Setting

2020 ◽  
Vol 41 (S1) ◽  
pp. s114-s115
Author(s):  
Alexandra Johnson ◽  
Bobby Warren ◽  
Deverick John Anderson ◽  
Melissa Johnson ◽  
Isabella Gamez ◽  
...  
Keyword(s):  
Real World ◽  
Medical Center ◽  
Academic Medical Center ◽  
Randomized Study ◽  
Healthcare Providers ◽  
Clinical Workflow ◽  
Provider Type ◽  
Academic Medical ◽  
Rn Students ◽  
The Impact

Background: Stethoscopes are a known vector for microbial transmission; however, common strategies used to clean stethoscopes pose certain barriers that prevent routine cleaning after every use. We aimed to determine whether using readily available alcohol-based hand rub (ABHR) would effectively reduce bacterial bioburden on stethoscopes in a real-world setting. Methods: We performed a randomized study on inpatient wards of an academic medical center to assess the impact of using ABHR (AlcareExtra; ethyl alcohol, 80%) on the bacterial bioburden of stethoscopes. Stethoscopes were obtained from healthcare providers after routine use during an inpatient examination and were randomized to control (no intervention) or ABHR disinfection (2 pumps applied to tubing and bell or diaphragm by study personnel, then allowed to dry). Cultures of the tubing and bell or diaphragm were obtained with premoistened cellulose sponges. Sponges were combined with 1% Tween20-PBS and mixed in the Seward Stomacher. The homogenate was centrifuged and all but ~5 mL of the supernatant was discarded. Samples were plated on sheep’s blood agar and selective media for clinically important pathogens (CIPs) including S. aureus, Enterococcus spp, and gram-negative bacteria (GNB). CFU count was determined by counting the number of colonies on each plate and using dilution calculations to calculate the CFU of the original ~5 mL homogenate. Results: In total, 80 stethoscopes (40 disinfection, 40 control) were sampled from 46 physicians (MDs) and MD students (57.5%), 13 advanced practice providers (16.3%), and 21 nurses (RNs) and RN students (26.3%). The median CFU count was ~30-fold lower in the disinfection arm compared to control (106 [IQR, 50–381] vs 3,320 [986–4,834]; P < .0001). The effect was consistent across provider type, frequency of recent usual stethoscope cleaning, age, and status of pet ownership (Fig. 1). Overall, 26 of 80 (33%) of stethoscopes harbored CIP. The presence of CIP was lower but not significantly different for stethoscopes that underwent disinfection versus controls: S. aureus (25% vs 32.5%), Enterococcus (2.5% vs 10%), and GNB (2.5% vs 5%). Conclusions: Stethoscopes may serve as vectors for clean hands to become recontaminated immediately prior to performing patient care activities. Using ABHR to clean stethoscopes after every use is a practical and effective strategy to reduce overall bacterial contamination that can be easily incorporated into clinical workflow. Larger studies are needed to determine the efficacy of ABHR at removing CIP from stethoscopes as stethoscopes in both arms were frequently contaminated with CIP. Prior cleaning of stethoscopes on the study day did not seem to impact contamination rates, suggesting the impact of alcohol foam disinfection is short-lived and may need to be repeated frequently (ie, after each use).Funding: NoneDisclosures: NoneDisclosures: NoneFunding: None

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