scholarly journals The first Antechinus reference genome provides a resource for investigating the genetic basis of semelparity and age-related neuropathologies

2020 ◽  
Author(s):  
Parice A. Brandies ◽  
Simon Tang ◽  
Robert S.P. Johnson ◽  
Carolyn J. Hogg ◽  
Katherine Belov
Keyword(s):  
Comparative Genomics ◽  
Y Chromosome ◽  
Reproductive Strategy ◽  
Genetic Basis ◽  
Reference Genome ◽  
Disease Model ◽  
Future Research ◽  
Transcriptome Data ◽  
Age Related ◽  
Antechinus Stuartii

AbstractAntechinus are a genus of mouse-like marsupials that exhibit a rare reproductive strategy known as semelparity and also naturally develop age-related neuropathologies similar to those in humans. We provide the first annotated antechinus reference genome for the brown antechinus (Antechinus stuartii). The reference genome is 3.3Gb in size with a scaffold N50 of 73Mb and 93.3% complete mammalian BUSCOs. Using bioinformatic methods we assign scaffolds to chromosomes and identify 0.78Mb of Y-chromosome scaffolds. Comparative genomics revealed interesting expansions in the NMRK2 gene and the protocadherin gamma family, which have previously been associated with aging and age-related dementias respectively. Transcriptome data displayed expression of common Alzheimer’s related genes in the antechinus brain and highlight the potential of utilising the antechinus as a future disease model. The valuable genomic resources provided herein will enable future research to explore the genetic basis of semelparity and age-related processes in the antechinus.

scholarly journals The first Antechinus reference genome provides a resource for investigating the genetic basis of semelparity and age-related neuropathologies

Gigabyte ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-22
Author(s):  
Parice A. Brandies ◽  
Simon Tang ◽  
Robert S. P. Johnson ◽  
Carolyn J. Hogg ◽  
Katherine Belov
Keyword(s):  
Comparative Genomics ◽  
Y Chromosome ◽  
Reproductive Strategy ◽  
Genetic Basis ◽  
Reference Genome ◽  
Disease Model ◽  
Future Research ◽  
Transcriptome Data ◽  
Age Related ◽  
Antechinus Stuartii

Antechinus are a genus of mouse-like marsupials that exhibit a rare reproductive strategy known as semelparity and also naturally develop age-related neuropathologies similar to those in humans. We provide the first annotated antechinus reference genome for the brown antechinus (Antechinus stuartii). The reference genome is 3.3 Gb in size with a scaffold N50 of 73Mb and 93.3% complete mammalian BUSCOs. Using bioinformatic methods we assign scaffolds to chromosomes and identify 0.78 Mb of Y-chromosome scaffolds. Comparative genomics revealed interesting expansions in the NMRK2 gene and the protocadherin gamma family, which have previously been associated with aging and age-related dementias respectively. Transcriptome data displayed expression of common Alzheimer’s related genes in the antechinus brain and highlight the potential of utilising the antechinus as a future disease model. The valuable genomic resources provided herein will enable future research to explore the genetic basis of semelparity and age-related processes in the antechinus.

scholarly journals Mitochondrial Respiration Changes in R6/2 Huntington’s Disease Model Mice during Aging in a Brain Region Specific Manner

2020 ◽  
Vol 21 (15) ◽  
pp. 5412 ◽  
Author(s):  
Johannes Burtscher ◽  
Alba Di Pardo ◽  
Vittorio Maglione ◽  
Christoph Schwarzer ◽  
Ferdinando Squitieri
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Disease Model ◽  
Brain Regions ◽  
Future Research ◽  
Adult Mice ◽  
Age Related ◽  
Developmental Shift ◽  
Regional Vulnerability ◽  
Oxygen Conditions

Mitochondrial dysfunction is crucially involved in aging and neurodegenerative diseases, such as Huntington’s Disease (HD). How mitochondria become compromised in HD is poorly understood but instrumental for the development of treatments to prevent or reverse resulting deficits. In this paper, we investigate whether oxidative phosphorylation (OXPHOS) differs across brain regions in juvenile as compared to adult mice and whether such developmental changes might be compromised in the R6/2 mouse model of HD. We study OXPHOS in the striatum, hippocampus, and motor cortex by high resolution respirometry in female wild-type and R6/2 mice of ages corresponding to pre-symptomatic and symptomatic R6/2 mice. We observe a developmental shift in OXPHOS-control parameters that was similar in R6/2 mice, except for cortical succinate-driven respiration. While the LEAK state relative to maximal respiratory capacity was reduced in adult mice in all analyzed brain regions, succinate-driven respiration was reduced only in the striatum and cortex, and NADH-driven respiration was higher as compared to juvenile mice only in the striatum. We demonstrate age-related changes in respirational capacities of different brain regions with subtle deviations in R6/2 mice. Uncovering in situ oxygen conditions and potential substrate limitations during aging and HD disease progression are interesting avenues for future research to understand brain-regional vulnerability in HD.

scholarly journals Spontaneous Eye Blinks Predict Executive Functioning in Seniors

2021 ◽  
Author(s):  
Jessika I. V. Buitenweg ◽  
Jaap M. J. Murre ◽  
K. Richard Ridderinkhof
Keyword(s):  
Older Adults ◽  
Working Memory ◽  
Executive Functioning ◽  
Cognitive Training ◽  
Functional Decline ◽  
Future Research ◽  
Blink Rate ◽  
Memory Updating ◽  
Age Related ◽  
Working Memory Updating

AbstractAs the world’s population is aging rapidly, cognitive training is an extensively used approach to attempt improvement of age-related cognitive functioning. With increasing numbers of older adults required to remain in the workforce, it is important to be able to reliably predict future functional decline, as well as the individual advantages of cognitive training. Given the correlation between age-related decline and striatal dopaminergic function, we investigated whether eye blink rate (EBR), a non-invasive, indirect indicator of dopaminergic activity, could predict executive functioning (response inhibition, switching and working memory updating) as well as trainability of executive functioning in older adults. EBR was collected before and after a cognitive flexibility training, cognitive training without flexibility, or a mock training. EBR predicted working memory updating performance on two measures of updating, as well as trainability of working memory updating, whereas performance and trainability in inhibition and switching tasks could not be predicted by EBR. Our findings tentatively indicate that EBR permits prediction of working memory performance in older adults. To fully interpret the relationship with executive functioning, we suggest future research should assess both EBR and dopamine receptor availability among seniors.

Looking to the horizon: the role of bilirubin in the development and prevention of age-related chronic diseases

2015 ◽  
Vol 129 (1) ◽  
pp. 1-25 ◽  
Author(s):  
Karl-Heinz Wagner ◽  
Marlies Wallner ◽  
Christine Mölzer ◽  
Silvia Gazzin ◽  
Andrew Cameron Bulmer ◽  
...  
Keyword(s):  
Disease Resistance ◽  
Chronic Diseases ◽  
Elevated Serum ◽  
Future Research ◽  
Bile Pigment ◽  
Therapeutic Modalities ◽  
Age Related ◽  
All Cause Mortality ◽  
Novel Biomarkers ◽  
Future Research Directions

Bilirubin, the principal tetrapyrrole, bile pigment and catabolite of haem, is an emerging biomarker of disease resistance, which may be related to several recently documented biological functions. Initially believed to be toxic in infants, the perception of bilirubin has undergone a transformation: it is now considered to be a molecule that may promote health in adults. Data from the last decade demonstrate that mildly elevated serum bilirubin levels are strongly associated with reduced prevalence of chronic diseases, particularly cardiovascular diseases (CVDs), as well as CVD-related mortality and risk factors. Recent data also link bilirubin to other chronic diseases, including cancer and Type 2 diabetes mellitus, and to all-cause mortality. Therefore, there is evidence to suggest that bilirubin is a biomarker for reduced chronic disease prevalence and a predictor of all-cause mortality, which is of important clinical significance. In the present review, detailed information on the association between bilirubin and all-cause mortality, as well as the pathological conditions of CVD, cancer, diabetes and neurodegenerative diseases, is provided. The mechanistic background concerning how bilirubin and its metabolism may influence disease prevention and its clinical relevance is also discussed. Given that the search for novel biomarkers of these diseases, as well as for novel therapeutic modalities, is a key research objective for the near future, bilirubin represents a promising candidate, meeting the criteria of a biomarker, and should be considered more carefully in clinical practice as a molecule that might provide insights into disease resistance. Clearly, however, greater molecular insight is warranted to support and strengthen the conclusion that bilirubin can prevent disease, with future research directions also proposed.

scholarly journals Strategies and cognitive reserve to preserve lexical production in aging

GeroScience ◽  
2021 ◽  
Author(s):  
Monica Baciu ◽  
Sonja Banjac ◽  
Elise Roger ◽  
Célise Haldin ◽  
Marcela Perrone-Bertolotti ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Aging ◽  
Individual Variability ◽  
Future Research ◽  
Aging Effects ◽  
Main Hypothesis ◽  
Compensatory Strategies ◽  
Age Related ◽  
Complementary Domain

AbstractIn the absence of any neuropsychiatric condition, older adults may show declining performance in several cognitive processes and among them, in retrieving and producing words, reflected in slower responses and even reduced accuracy compared to younger adults. To overcome this difficulty, healthy older adults implement compensatory strategies, which are the focus of this paper. We provide a review of mainstream findings on deficient mechanisms and possible neurocognitive strategies used by older adults to overcome the deleterious effects of age on lexical production. Moreover, we present findings on genetic and lifestyle factors that might either be protective or risk factors of cognitive impairment in advanced age. We propose that “aging-modulating factors” (AMF) can be modified, offering prevention opportunities against aging effects. Based on our review and this proposition, we introduce an integrative neurocognitive model of mechanisms and compensatory strategies for lexical production in older adults (entitled Lexical Access and Retrieval in Aging, LARA). The main hypothesis defended in LARA is that cognitive aging evolves heterogeneously and involves complementary domain-general and domain-specific mechanisms, with substantial inter-individual variability, reflected at behavioral, cognitive, and brain levels. Furthermore, we argue that the ability to compensate for the effect of cognitive aging depends on the amount of reserve specific to each individual which is, in turn, modulated by the AMF. Our conclusion is that a variety of mechanisms and compensatory strategies coexist in the same individual to oppose the effect of age. The role of reserve is pivotal for a successful coping with age-related changes and future research should continue to explore the modulating role of AMF.

scholarly journals Hyperinsulinemia and Its Pivotal Role in Aging, Obesity, Type 2 Diabetes, Cardiovascular Disease and Cancer

2021 ◽  
Vol 22 (15) ◽  
pp. 7797
Author(s):  
Joseph A. M. J. L. Janssen
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Insulin Secretion ◽  
Early Stage ◽  
Insulin Clearance ◽  
Future Research ◽  
Age Related ◽  
Hepatic Insulin Clearance

For many years, the dogma has been that insulin resistance precedes the development of hyperinsulinemia. However, recent data suggest a reverse order and place hyperinsulinemia mechanistically upstream of insulin resistance. Genetic background, consumption of the “modern” Western diet and over-nutrition may increase insulin secretion, decrease insulin pulses and/or reduce hepatic insulin clearance, thereby causing hyperinsulinemia. Hyperinsulinemia disturbs the balance of the insulin–GH–IGF axis and shifts the insulin : GH ratio towards insulin and away from GH. This insulin–GH shift promotes energy storage and lipid synthesis and hinders lipid breakdown, resulting in obesity due to higher fat accumulation and lower energy expenditure. Hyperinsulinemia is an important etiological factor in the development of metabolic syndrome, type 2 diabetes, cardiovascular disease, cancer and premature mortality. It has been further hypothesized that nutritionally driven insulin exposure controls the rate of mammalian aging. Interventions that normalize/reduce plasma insulin concentrations might play a key role in the prevention and treatment of age-related decline, obesity, type 2 diabetes, cardiovascular disease and cancer. Caloric restriction, increasing hepatic insulin clearance and maximizing insulin sensitivity are at present the three main strategies available for managing hyperinsulinemia. This may slow down age-related physiological decline and prevent age-related diseases. Drugs that reduce insulin (hyper) secretion, normalize pulsatile insulin secretion and/or increase hepatic insulin clearance may also have the potential to prevent or delay the progression of hyperinsulinemia-mediated diseases. Future research should focus on new strategies to minimize hyperinsulinemia at an early stage, aiming at successfully preventing and treating hyperinsulinemia-mediated diseases.

scholarly journals Health Among Sexual Minority Older Adults: Individual Differences and Implications for Improving Health

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 860-860
Author(s):  
Britney Wardecker ◽  
Cara Exten
Keyword(s):  
Older Adults ◽  
Individual Differences ◽  
Sexual Minority ◽  
Health Care Access ◽  
Psychological Health ◽  
Negative Mood ◽  
Health Problems ◽  
Future Research ◽  
Care Access ◽  
Age Related

Abstract The number of sexual minority (SM) older adults is increasing rapidly, yet this population continues to be underrepresented in research (Fredriksen-Goldsen & Kim, 2017) and experiences significant disparities in health and health care access (Fredriksen-Goldsen, 2016; Wallace et al., 2011). In the current symposium, we analyze data from U.S. national probability samples of middle-aged and older adults (MIDUS, HRS, NESARC-III) to consider how age-related concerns and challenges may be experienced differently by SM individuals compared to their heterosexual counterparts. This symposium includes novel methods and statistical tools, such as daily diary assessments, multilevel modeling, and time-varying effects models. Individual presentations evaluate how: (1) SM women, compared to heterosexual women, may respond differently to menopause through norms and values surrounding womanhood; (2) midlife and older SM individuals use alcohol and cigarettes more frequently across a typical week than their heterosexual counterparts, though their substance use may not be tied to common triggers (e.g., negative mood, stress); (3) despite bisexual older adults reporting more health problems compared to lesbian and gay counterparts, they are less prepared for health concerns and crises (e.g., reporting a lower number of valid wills); and (4) the prevalence of depression and anxiety varies across age, such that older SM adults—especially women—are particularly vulnerable to psychological health problems. These presentations collectively examine complex issues facing older SM adults while emphasizing individual differences (i.e., women’s concerns, bisexual people’s issues). We discuss challenges in researching this growing at-risk population, and we highlight areas of future research and intervention.

scholarly journals Apoptosis in the Extraosseous Calcification Process

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 131
Author(s):  
Federica Boraldi ◽  
Francesco Demetrio Lofaro ◽  
Daniela Quaglino
Keyword(s):  
Genetic Basis ◽  
Membrane Vesicles ◽  
Matrix Vesicles ◽  
Apoptotic Bodies ◽  
Connective Tissues ◽  
Mineralization Process ◽  
Mitochondrial Alterations ◽  
Age Related ◽  
And Oxidative Stress ◽  
And Cartilage

Extraosseous calcification is a pathologic mineralization process occurring in soft connective tissues (e.g., skin, vessels, tendons, and cartilage). It can take place on a genetic basis or as a consequence of acquired chronic diseases. In this last case, the etiology is multifactorial, including both extra- and intracellular mechanisms, such as the formation of membrane vesicles (e.g., matrix vesicles and apoptotic bodies), mitochondrial alterations, and oxidative stress. This review is an overview of extraosseous calcification mechanisms focusing on the relationships between apoptosis and mineralization in cartilage and vascular tissues, as these are the two tissues mostly affected by a number of age-related diseases having a progressively increased impact in Western Countries.

PSXII-2 Identification of candidate SNPs associated with high prolificacy in Romanov sheep

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 254-255
Author(s):  
Alexey V Shakhin ◽  
Arsen V Dotsev ◽  
Tatiana E Deniskova ◽  
Gottfried Brem ◽  
Natalia A Zinovieva
Keyword(s):  
Higher Education ◽  
Genetic Basis ◽  
Reference Genome ◽  
Unique Property ◽  
Candidate Snps ◽  
Merino Sheep ◽  
Sheep Breeds ◽  
Important Trait ◽  
Very High ◽  
Selection Of

Abstract Prolificacy is a very important trait in sheep. Romanov sheep, the well-known Russian sheep breed, are characterized by very high prolificacy; however, the genetic basis of this unique property of Romanov sheep is still unknown. It was reported that Ovine BMPR1B gene, located on the OAR6, is associated with prolificacy in several sheep breeds. The aim of our study was to identify candidate SNPs within BMPR1B gene, related to prolificacy. To achieve this goal, using NGS technology, we sequenced ovine BMPR1B gene in Romanov sheep (n = 6), which are characterized by high prolificacy (about 270 lambs per 100 ewes). The sequences of BMPR1B gene of Noire du Velay, Tan, Southdown and Australian Horned Merino sheep breeds as well as Asiatic mouflon (n = 1), which are characterized by significantly lower prolificacy (from 110 to 180 lambs per 100 ewes) were derived from publicly available sources and used for comparison. FST analysis performed in PLINK 1.9 program revealed 10 SNPs with values higher than 0.8. The majority of candidate SNPs under putative selection were localized in the region from 29,382,098 to 29,430,387 on OAR6 of Ovine reference genome (Oar_v3.1 (Ensembl release 98). Thus, we can suggest, that this region of the BMPR1B gene can be considered as the putative region, associated with high prolificacy of Romanov sheep. Additional studies will be needed to confirm the effect of identified candidate SNPs on prolificacy traits. The research results will be useful for artificial selection of sheep with higher prolific capacity, including the introduction of desired alleles in sheep populations using genome editing technologies. This work was supported by the Russian Ministry of Science and Higher Education No. 0445-2019-0024 and RFBR No. 20-516-56002.

Loss of the Y Chromosome: An Age-Related or Clonal Phenomenon in Acute Myelogenous Leukemia/Myelodysplastic Syndrome?

2008 ◽  
Vol 132 (8) ◽  
pp. 1329-1332
Author(s):  
Anna K. Wong ◽  
Belle Fang ◽  
Ling Zhang ◽  
Xiuqing Guo ◽  
Stephen Lee ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Y Chromosome ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Related Phenomenon ◽  
Patients Âgés ◽  
Age Related ◽  
Acute Myelogenous ◽  
Bone Marrow Analysis

Abstract Context.—The clinical association between loss of the Y chromosome and acute myelogenous leukemia and myelodysplastic syndrome (AML/MDS) has been debated because both phenomena are related to aging. A prior publication suggests that loss of the Y chromosome in more than 75% of cells may indicate a clonal phenomenon that could be a marker for hematologic disease. Objective.—To evaluate the relationship between loss of the Y chromosome and AML/MDS. Design.—A retrospective review of cytogenetic reports of 2896 male patients ascertained from 1996 to 2007 was performed. Results were stratified based on the percentage of cells missing the Y chromosome and were correlated with patients' ages and bone marrow biopsy reports through logistic regression analysis with adjustment for age. Results.—Loss of the Y chromosome was found in 142 patients. Of these, 16 patients demonstrated myeloid disease, with 2 cases of AML and 14 cases of MDS. An increased incidence (P < .05) of AML/MDS was seen only in the group composed of 8 patients with complete loss of the Y chromosome in all karyotyped cells (1 case of AML and 7 cases of MDS). Conclusion.—Loss of the Y chromosome appears to be primarily an age-related phenomenon. However, in individuals in which all cells on cytogenetic analysis showed loss of the Y chromosome, there was a statistically significant increase in AML/MDS, suggesting that the absence of any normal-dividing cells in a bone marrow analysis may be indicative of AML/MDS.

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