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

2021 ◽  
pp. 1-6
Author(s):  
Justina Koubová ◽  
Radmila Čapková Frydrychová

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.

2014 ◽  
Vol 128 (6) ◽  
pp. 367-377 ◽  
Author(s):  
Yun Lin ◽  
Amanda Damjanovic ◽  
E. Jeffrey Metter ◽  
Huy Nguyen ◽  
Thai Truong ◽  
...  

The present longitudinal study reveals that the telomere length change with age in vivo differs among individuals and in different cell types and is influenced by telomerase activity, naïve T-cell percentage and changes in physiological conditions such as glucose and interleukin-6 levels.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Justina Koubová ◽  
Michala Sábová ◽  
Miloslav Brejcha ◽  
Dalibor Kodrík ◽  
Radmila Čapková Frydrychová

AbstractIn honeybees (Apis mellifera), the rate of aging is modulated through social interactions and according to caste differentiation and the seasonal (winter/summer) generation of workers. Winter generation workers, which hatch at the end of summer, have remarkably extended lifespans as an adaptation to the cold season when the resources required for the growth and reproduction of colonies are limited and the bees need to maintain the colony until the next spring. In contrast, the summer bees only live for several weeks. To better understand the lifespan differences between summer and winter bees, we studied the fat bodies of honeybee workers and identified several parameters that fluctuate in a season-dependent manner. In agreement with the assumption that winter workers possess greater fat body mass, our data showed gradual increases in fat body mass, the size of the fat body cells, and Vg production as the winter season proceeded, as well as contrasting gradual decreases in these parameters in the summer season. The differences in the fat bodies between winter and summer bees are accompanied by respective increases and decreases in telomerase activity and DNA replication in the fat bodies. These data show that although the fat bodies of winter bees differ significantly from those of summer bees, these differences are not a priori set when bees hatch at the end of summer or in early autumn but instead gradually evolve over the course of the season, depending on environmental factors.


Author(s):  
Jose C. Noguera ◽  
Alberto Velando

In wild animals, telomere attrition during early development has been linked with several fitness penalties throughout life. Telomerase enzyme can elongate telomeres, but it is generally assumed that its activity is suppressed in most somatic tissues upon birth. However, recent evidence suggests that this may not be the rule for long-lived bird species. We have therefore investigated whether telomerase activity is maintained during the postnatal growth period in a wild yellow-legged gull (Larus michahellis) population. Our results indicate that telomerase activity is not negligible in the blood cells, but activity levels sharply decline from hatching to fledging following a similar pattern to that observed in telomere length. Our results further suggest that the observed variation in telomere length may be the result of a negative effect of fast growth on telomerase activity, thus providing a new mechanism through which growth rates may affect telomere dynamics and potentially life-history trajectories.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 367-367
Author(s):  
Bradley Willcox ◽  
Richard Allsopp ◽  
Peter Martin

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.


Author(s):  
Radmila Capkova Frydrychova

Telomerase activity and telomere restoration in certain somatic cells of human adults maintain the proliferative capacity of these cells and contribute to their regenerative potential, and telomerase activity and telomere length are commonly considered lifespan predictors. Eusocial insects provide excellent model systems for aging research based on their extraordinary caste-related lifespan differences that contradict the typical fecundity/lifespan trade-off. In agreement with the common presumption, telomerase activity is upregulated in the reproductive, long-lived individuals of eusocial insects such as queens and kings, proposing that telomerase activity acts as a key factor in their extended longevity. But, as documented by the presence of telomerase in somatic tissues of numerous invertebrate and vertebrate species, the connection between telomerase activity and the predicted lifespan is not clear. Here, I ask whether somatic telomerase activity in eusocial reproductives may serve its non-canonical function to protect its individuals against the exacerbated metabolic stress upon reproduction and be a reflection of a more common phenomenon among species. I propose a hypothesis that the presence of telomerase activity in somatic cells reflects a different reproduction strategy of the species.


2021 ◽  
Vol 43 (2) ◽  
pp. 767-781
Author(s):  
Vanessa Pinatto Gaspar ◽  
Anelise Cardoso Ramos ◽  
Philippe Cloutier ◽  
José Renato Pattaro Junior ◽  
Francisco Ferreira Duarte Junior ◽  
...  

KIN (Kin17) protein is overexpressed in a number of cancerous cell lines, and is therefore considered a possible cancer biomarker. It is a well-conserved protein across eukaryotes and is ubiquitously expressed in all cell types studied, suggesting an important role in the maintenance of basic cellular function which is yet to be well determined. Early studies on KIN suggested that this nuclear protein plays a role in cellular mechanisms such as DNA replication and/or repair; however, its association with chromatin depends on its methylation state. In order to provide a better understanding of the cellular role of this protein, we investigated its interactome by proximity-dependent biotin identification coupled to mass spectrometry (BioID-MS), used for identification of protein–protein interactions. Our analyses detected interaction with a novel set of proteins and reinforced previous observations linking KIN to factors involved in RNA processing, notably pre-mRNA splicing and ribosome biogenesis. However, little evidence supports that this protein is directly coupled to DNA replication and/or repair processes, as previously suggested. Furthermore, a novel interaction was observed with PRMT7 (protein arginine methyltransferase 7) and we demonstrated that KIN is modified by this enzyme. This interactome analysis indicates that KIN is associated with several cell metabolism functions, and shows for the first time an association with ribosome biogenesis, suggesting that KIN is likely a moonlight protein.


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 749-749
Author(s):  
Jason Sanders

Abstract Excellent pulmonary function is one of the strongest predictors of longevity across animal models and human populations. Unfortunately, none of the major age-associated pulmonary diseases – obstructive lung disease, pulmonary fibrosis, and increased susceptibility to pneumonia – have strongly effective disease modifying therapies. There is growing evidence that normal age-associated decline in pulmonary function and major age-associated pulmonary diseases are linked to the hallmarks of aging including senescence, nutrient signaling dysregulation, mitochondrial dysfunction, and telomere disorders. This presents opportunities for collaboration between gerontologists and pulmonologists to unravel age-associated developmental mechanisms and design novel treatments. In this symposium, leaders in pulmonary aging research will present novel data on links between aging and pulmonary health and geroscience-based interventions under study. Dr. Sanders will provide an overview of the scientific and clinical space and present epidemiologic associations between aging biomarkers, early pulmonary fibrosis, and mortality. Dr. Le Saux will discuss senescence and specifically how eicosanoid biology may explain organ-specific patterns of senescence-associated fibrosis. Dr. Thannickal will discuss age-associated perturbations in metabolism and mitochondrial function and targeting these pathways to improve lung function and treat pulmonary diseases. Dr. Newton will discuss mechanisms and clinical applications of telomere biology to pulmonary aging. Symposium attendees will (1) be poised to generate collaborations between gerontologists and pulmonologists to address existing knowledge gaps in mechanisms of pulmonary aging, and (2) develop a better understanding of translational opportunities to design geroscience-based diagnostics and therapeutics to improve pulmonary health with aging.


2002 ◽  
Vol 283 (2) ◽  
pp. L297-L304 ◽  
Author(s):  
Larissa A. Shimoda ◽  
Laura E. Welsh ◽  
David B. Pearse

Endothelial barrier dysfunction is typically triggered by increased intracellular Ca2+concentration. Membrane-permeable analogs of guanosine 3′,5′-cyclic monophosphate (cGMP) prevent disruption of endothelial cell integrity. Because membrane potential ( E m), which influences the electrochemical gradient for Ca2+ influx, is regulated by K+ channels, we investigated the effect of 8-bromo-cGMP on E m and inwardly rectifying K+ (KIR) currents in bovine pulmonary artery and microvascular endothelial cells (BPAEC and BMVEC), using whole cell patch-clamp techniques. Both cell types exhibited inward currents at potentials negative to −50 mV that were abolished by application of 10 μM Ba2+, consistent with KIR current. Ba2+ also depolarized both cell types. 8-Bromo-cGMP (10−3 M) depolarized BPAEC and BMVEC and inhibited KIR current. Pretreatment with Rp-8-cPCT-cGMPS or KT-5823, protein kinase G (PKG) antagonists, did not prevent current inhibition by 8-bromo-cGMP. These data suggest that 8-bromo-cGMP induces depolarization in BPAEC and BMVEC due, in part, to PKG-independent inhibition of KIR current. The depolarization could be a protective mechanism that prevents endothelial cell barrier dysfunction by reducing the driving force for Ca2+ entry.


2020 ◽  
Vol 66 (4) ◽  
pp. 35-44
Author(s):  
Ekaterina N. Dudinskaya ◽  
Olga N. Tkacheva ◽  
Natalia V. Brailova ◽  
Irina D. Strazhesko ◽  
Marina V. Shestakova

BACKGROUND: Insulin resistance accelerates the aging process, but its speed depends on the individual characteristics of the metabolism. One of the reasons for the different aging rates in individuals with insulin resistance is the initially different “genetic protection” of cells, which many scientists associate with replicative cellular aging.AIMS: to study the relationship between the state of carbohydrate metabolism and markers of replicative cell aging in individuals with different sensitivity to insulin.MATERIALS AND METHODS: The observation study included 305 patients. The parameters of glucose metabolism and telomere biology were studied.RESULTS: The mean age of the patients was 51.5±13.3 years. Patients were divided into three groups depending on presence of insulin resistance: healthy, with insulin resistance and with type 2 diabetes. The mean age of healthy patients was 48.82±13.87 years, in insulin resistance group — 53.04±12.8, in 2 diabetes mellitus — 58.4±7.90. The median telomere length was 9.76. The median telomerase activity was 0.48. Both telomere length and telomerase activity progressively decrease as insulin resistance increases. In patients with diabetes, short telomere lengths and low telomerase activity predominated. The insulin resistance index has the greatest impact on the risk of detecting “short” telomeres. In patients with insulin resistance, an increase in glycated hemoglobin increases the likelihood of detecting short telomeres by 2.4 times, and in diabetes mellitus by 4.26 times, an increase in fasting plasma glucose by 90%, and an increase in HOMA-IR by 35%. An increase in insulin resistance increases the risk of detecting «low» telomerase activity by 53% and the risk of detecting «very low» telomerase activity by 92%. A decrease in synsulin resistance increases the chance of increasing telomerase activity to «very high» by 51%.CONCLUSION: Shorter telomeres are associated with more pronounced disorders of carbohydrate metabolism and a higher degree of insulin resistance. Further studies of metabolic status are necessary to personalize their lifestyle and treatment goals.


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