scholarly journals Cell strain-derived induced pluripotent stem cell as a genetically controlled approach to investigate age-related host response to flaviviral infection

2021 ◽  
Author(s):  
Amanda M. Bifani ◽  
Hwee Cheng Tan ◽  
Milly M. Choy ◽  
Eng Eong Ooi
Keyword(s):  
Older Adults ◽  
Host Response ◽  
Severe Dengue ◽  
Type I ◽  
Differentiated Cells ◽  
Age Related ◽  
Increased Risk ◽  
Cell Strains ◽  
Induced Pluripotent

The expansion of the geographical footprint of dengue viruses (DENVs) and their mosquito vectors have affected more than half of the global population, including older adults who appear to show elevated risk of severe dengue. Despite this epidemiological trend, how ageing contributes to increase dengue pathogenesis is poorly understood. A limitation has been the lack of useful in vitro experimental approaches; cell lines commonly used for infection studies are immortal and hence do not age. Cell strains, such as WI-38 and MRC-5 with diploid genomes, do age with in vitro passaging but these cell strains were isolated decades ago and are now mostly highly passaged. Herein, we show that reprogramming of cell strains with finite lifespan into induced pluripotent stem cells (iPSCs), followed by conversion back into terminally differentiated cells, can be an approach to derive genetically identical cells at different stages of ageing. The iPSC-derived differentiated cells were susceptible to wild-type DENV infection and produced greater levels of type-I interferon expression with increase passaging, despite similar levels of infection. In contrast, infection with the attenuated DENV-2 PDK53 and YF17D-204 strains showed reduced and increased levels of infection with increasing passages; the latter could be clinically pertinent as YF17D-204 vaccination in older adults is associated with increased risk of severe adverse outcome. The differences in infection susceptibility and host response collectively suggest the potential of iPSC-derived cell strains as a genetically controlled approach to understand how ageing impacts viral pathogenesis. Importance Ageing has been a risk factor for poor clinical outcome in several infectious diseases, including dengue. However, age-dependent responses to dengue and other flaviviral infection or vaccination have remained incompletely understood due partly to lack of suitable laboratory tools. We thus developed an in vitro approach to examine age-related changes in host response to flaviviral infection. Notably, this approach uses cell strains with diploid rather than aneuploidic genomes, which are unstable. Conversion of these cells into iPSCs ensure sustainability of this resource and reprogramming back into terminally differentiated cells would, even with limited number of passages, produce cells at different stages of ageing for infection studies. Our findings suggest that this in vitro system has the potential to serve as a genetically-controlled approach to define the age-related response to flavivirus infection.

Association between Vitamins and Minerals with Antioxidant Effects and Coronary Artery Calcification in Adults and Older Adults: A Systematic Review

2019 ◽  
Vol 25 (22) ◽  
pp. 2474-2479 ◽  
Author(s):  
Alisson Diego Machado ◽  
Gustavo Rosa Gentil Andrade ◽  
Jéssica Levy ◽  
Sara Silva Ferreira ◽  
Dirce Maria Marchioni
Keyword(s):  
Systematic Review ◽  
Older Adults ◽  
Coronary Artery ◽  
Coronary Artery Calcification ◽  
Serum Levels ◽  
Antioxidant Compounds ◽  
Increased Risk ◽  
Coronary Events ◽  
Antioxidant Effects

Background: Coronary Artery Calcification (CAC) is considered an important cardiovascular risk factor. There is evidence that CAC is associated with an increased risk of atherosclerosis, coronary events and cardiovascular mortality. Inflammation is one of the factors associated with CAC and despite the interest in antioxidant compounds that can prevent CAC, its association with antioxidants remains unclear. Objective: This study aimed to systematically review the association between vitamins and minerals with antioxidant effects and CAC in adults and older adults. Methods: We conducted a systematic review using PubMed for articles published until October 2018. We included studies conducted in subjects aged 18 years and older with no previous cardiovascular disease. Studies involving animal or in vitro experiments and the ones that did not use reference methods to assess the CAC, dietary intake or serum levels of vitamin or mineral were excluded. Results: The search yielded 390 articles. After removal of duplicates, articles not related to the review, review articles, editorials, hypothesis articles and application of the inclusion and exclusion criteria, 9 articles remained. The results of the studies included in this systematic review suggest that magnesium is inversely associated with CAC and results on the association between CAC and vitamin E have been conflicting. Conclusion: Additional prospective studies are needed to elucidate the role of these micronutrients on CAC.

scholarly journals Electromyographic activation patterns during swallowing in older adults

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jin Young Ko ◽  
Hayoung Kim ◽  
Joonyoung Jang ◽  
Jun Chang Lee ◽  
Ju Seok Ryu
Keyword(s):  
Older Adults ◽  
Viscous Fluid ◽  
Muscle Activation ◽  
Fatty Infiltration ◽  
Liquid Volume ◽  
Type I ◽  
Type Ii ◽  
Activation Patterns ◽  
Muscle Activation Patterns ◽  
Age Related

AbstractAge-related weakness due to atrophy and fatty infiltration in oropharyngeal muscles may be related to dysphagia in older adults. However, little is known about changes in the oropharyngeal muscle activation pattern in older adults. This was a prospective and experimental study. Forty healthy participants (20 older [> 60 years] and 20 young [< 60 years] adults) were enrolled. Six channel surface electrodes were placed over the bilateral suprahyoid (SH), bilateral retrohyoid (RH), thyrohyoid (TH), and sternothyroid (StH) muscles. Electromyography signals were then recorded twice for each patient during swallowing of 2 cc of water, 5 cc of water, and 5 cc of a highly viscous fluid. Latency, duration, and peak amplitude were measured. The activation patterns were the same, in the order of SH, TH, and StH, in both groups. The muscle activation patterns were classified as type I and II; the type I pattern was characterized by a monophasic shape, and the type II comprised a pre-reflex phase and a main phase. The oropharyngeal muscles and SH muscles were found to develop a pre-reflex phase specifically with increasing volume and viscosity of the swallowed fluid. Type I showed a different response to the highly viscous fluid in the older group compared to that in the younger group. However, type II showed concordant changes in the groups. Therefore, healthy older people were found to compensate for swallowing with a pre-reflex phase of muscle activation in response to increased liquid volume and viscosity, to adjust for age-related muscle weakness.

HIV is associated with an increased risk of age-related clonal hematopoiesis among older adults

2021 ◽  
Author(s):  
Nila J. Dharan ◽  
Paul Yeh ◽  
Mark Bloch ◽  
Miriam M. Yeung ◽  
David Baker ◽  
...  
Keyword(s):  
Older Adults ◽  
Clonal Hematopoiesis ◽  
Age Related ◽  
Increased Risk

scholarly journals Age-Related Changes in Molecular and Whole Muscle Function: Role of Fat Content?

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 141-141
Author(s):  
Joseph Gordon III ◽  
Nicholas Remillard ◽  
Chad Straight ◽  
Rajakumar Nagarajan ◽  
Bruce Damon ◽  
...  
Keyword(s):  
Older Adults ◽  
Molecular Mechanisms ◽  
Fat Content ◽  
Fat Deposition ◽  
Muscle Size ◽  
Type I ◽  
Contraction Velocity ◽  
Age Related ◽  
Whole Muscle ◽  
Age Related Changes

Abstract Decreases in muscle size and function are a general consequence of old age; the precise mechanisms of these changes remain unclear. Recent studies suggest that fat deposition in muscle may also contribute to dysfunction in older adults. Fat content was quantified in the quadriceps, and its effects on function in healthy young (21-45 y) and older (65-75 y) men and women (n=44) of comparable physical activity were compared. A subset of the young matched with the older group for muscle fat content were also examined. Peak fat-free whole muscle cross-sectional area (mCSA; cm2), volume (MV; cm3), fat content (fat fraction, FF; %), specific torque (Nm/mCSA) and peak contraction velocity (Nm∙s-1) were determined using fat-water magnetic resonance imaging and dynamometry (0-300□∙s-1). To examine potential molecular mechanisms of muscle weakness, vastus lateralis biopsies were obtained (n=31) and cross-bridge kinetics of type I and II fibers were determined. FF was higher in older adults than young (8.4±1.2% (SE), 7.6±1.4; p=0.03), while mCSA (48.9±10.4 vs. 64.2±17.3), MV (1536±532 vs. 2112±708), specific torque (2.6±0.4 vs. 3.2±0.4), and peak voluntary contraction velocity (422±20 vs. 441±23) were lower in older than young (p&lt;0.01). Type II fiber myosin attachment rate was slower and attachment time longer in older muscle (p&lt;0.017), providing a potential mechanism for the slowing of peak contraction velocity with age. Notably, differences at the whole muscle and molecular levels remained for the subset of young and older groups matched for FF, suggesting that fat deposition in muscle does not exacerbate age-related changes in function.

scholarly journals Dual Effects of Hearing Loss and Dementia on Functional Limitations in Older Adults

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 214-214
Author(s):  
Michael McKee ◽  
Yunshu Zhou ◽  
Joshua Ehrlich ◽  
Elham Mahmoudi ◽  
Jennifer Deal ◽  
...  
Keyword(s):  
Older Adults ◽  
Hearing Loss ◽  
Self Care ◽  
Household Activity ◽  
Cross Sectional ◽  
Age Related ◽  
Increased Risk ◽  
Lower Mobility ◽  
Independent Effects ◽  
The Impact

Abstract Age-related hearing loss (HL) is both common and associated with elevated risk for cognitive decline and poorer health. To care for an aging population, it is critical to understand the effect of coexisting HL and dementia on functional activities. The effect of co-existing dementia and self-reported HL on daily functioning were assessed. A cross-sectional analysis was performed using nationally-representative data from the 2015 National Health and Aging Trends Study consisting of U.S. adults 65+. The sample included 1,829 adults with HL (22.8%) and 5,338 adults without HL. Multivariable Poisson regression was used to model the independent effects and interaction of self-reported HL and dementia status on three validated functional activity scales (self-care, mobility, and household). All analyses adjusted for sociodemographic and medical factors. HL participants were more likely to be white, older, male, less educated (p &lt;0.01). 8.4% had possible dementia and 6.5% had probable dementia. Respondents with HL or possible or probable dementia had significantly lower mobility, self-care, and household activity scores (p&lt;.001 for all comparisons) compared to their peers. A small yet significant interaction was present in all models, suggesting that HL respondents with co-occurring dementia had lower mobility, self-care, and household activity scores than predicted by the independent effects of dementia and self-reported HL (p&lt;.001 for all comparisons). Older adults with co-occurring dementia and HL are at increased risk for poor functioning and should be screened by healthcare providers. Future work should consider the impact of intervention in this vulnerable/at-risk population.

Tissue specificity of type I collagen gene expression is determined at both transcriptional and post-transcriptional levels

1984 ◽  
Vol 4 (9) ◽  
pp. 1843-1852
Author(s):  
R J Focht ◽  
S L Adams
Keyword(s):  
Gene Expression ◽  
Rna Structure ◽  
Type I Collagen ◽  
Translational Efficiency ◽  
Type I ◽  
Collagen Gene ◽  
Differentiated Cells ◽  
Collagen Gene Expression

We analyzed the control of type I collagen synthesis in four kinds of differentiated cells from chicken embryos which synthesize very different amounts of the protein. Tendon, skin, and smooth muscle cells were found to have identical amounts of type I collagen RNAs; however, the RNAs had inherently different translatabilities, which were observed both in vivo and in vitro. Chondrocytes also had substantial amounts of type I collagen RNAs, even though they directed no detectable synthesis of the protein either in vivo or in vitro. Type I collagen RNAs in chondrocytes display altered electrophoretic mobilities, suggesting that in these cells the reduction in translational efficiency may be mediated in part by changes in the RNA structure. These data indicate that control of type I collagen gene expression is a complex process which is exerted at both transcriptional and post-transcriptional levels.

scholarly journals Coenzyme Q10, Ageing and the Nervous System: An Overview

Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 2
Author(s):  
David Mantle ◽  
Robert A. Heaton ◽  
Iain P. Hargreaves
Keyword(s):  
Oxidative Stress ◽  
Coenzyme Q10 ◽  
Neurological Disorders ◽  
Neurological Disease ◽  
Age Related ◽  
Increased Risk ◽  
Potential Therapeutic Role ◽  
Ageing Brain ◽  
And Oxidative Stress

The ageing brain is characterised by changes at the physical, histological, biochemical and physiological levels. This ageing process is associated with an increased risk of developing a number of neurological disorders, notably Alzheimer’s disease and Parkinson’s disease. There is evidence that mitochondrial dysfunction and oxidative stress play a key role in the pathogenesis of such disorders. In this article, we review the potential therapeutic role in these age-related neurological disorders of supplementary coenzyme Q10, a vitamin-like substance of vital importance for normal mitochondrial function and as an antioxidant. This review is concerned primarily with studies in humans rather than in vitro studies or studies in animal models of neurological disease. In particular, the reasons why the outcomes of clinical trials supplementing coenzyme Q10 in these neurological disorders is discussed.

Physical and Cognitive Activity and Exercise for Older Adults: A Review

2005 ◽  
Vol 60 (2) ◽  
pp. 95-126 ◽  
Author(s):  
Michael Hogan
Keyword(s):  
Older Adults ◽  
Intervention Program ◽  
Tai Chi ◽  
Cognitive Activity ◽  
Aging Research ◽  
Tai Chi Chuan ◽  
Age Related ◽  
Increased Risk ◽  
Cognitive Exercise ◽  
System Resilience

Age-related reduction in musculoskeletal, cardiovascular, and central nervous system resilience can result in wide-ranging limitations in adaptive capacity associated with negative outcomes such as cognitive decline, increased risk of cardiovascular disease, mobility problems, and increased incidence of debilitating falls. This article reviews the benefits of both cognitive and physical activity within the broad context of multiple system resilience in adult aging. Research on a unique form of combined physical/cognitive exercise, Tai Chi Chuan, is presented. The relationship between physiological and psychological gain associated with an activity intervention program is discussed in light of principles of rehabilitation, intervention compliance, subjective and objective gain, and the hypothesized value of combining physical exercise, cognitive exercise, and relaxation into a single program designed to promote resilience in older adults.

Changes in the Dynamic Stability of Walking in Active Healthy Older Adults Independent of Changes in Walking Speed

2008 ◽  
Author(s):  
Hyun Gu Kang ◽  
Jonathan B. Dingwell
Keyword(s):  
Older Adults ◽  
Young Adults ◽  
Dynamic Stability ◽  
Walking Speed ◽  
Age Groups ◽  
Leg Strength ◽  
Age Related ◽  
Increased Risk ◽  
Risk Of Falls ◽  
Walking Speeds

Older adults commonly walk slower, which many believe helps improve their walking stability. However, they remain at increased risk of falls. We investigated how differences in age and walking speed independently affect dynamic stability during walking, and how age-related changes in leg strength and ROM affected this relationship. Eighteen active healthy older and 17 younger adults walked on a treadmill for 5 minutes each at each of 5 speeds (80–120% of preferred). Local divergence exponents and maximum Floquet multipliers (FM) were calculated to quantify each subject’s responses to small inherent perturbations during walking. These older adults exhibited the same preferred walking speeds as the younger subjects (p = 0.860). However, these older adults still exhibited greater local divergence exponents (p&lt;0.0001) and higher maximum FM (p&lt;0.007) than young adults at all walking speeds. These older adults remained more unstable (p&lt;0.04) even after adjusting for declines in both strength and ROM. In both age groups, local divergence exponents decreased at slower speeds and increased at faster speeds (p&lt;0.0001). Maximum FM showed similar changes with speed (p&lt;0.02). The older adults in this study were healthy enough to walk at normal speeds. However, these adults were still more unstable than the young adults, independent of walking speed. This greater instability was not explained by loss of leg strength and ROM. Slower speeds led to decreased instability in both groups.

scholarly journals Aging, Resistance Training, and Diabetes Prevention

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Kyle D. Flack ◽  
Kevin P. Davy ◽  
Matthew W. Hulver ◽  
Richard A. Winett ◽  
Madlyn I. Frisard ◽  
...  
Keyword(s):  
Older Adults ◽  
Resistance Training ◽  
Glucose Tolerance ◽  
Diabetes Prevention ◽  
Baby Boom ◽  
Related Factors ◽  
Age Related ◽  
Increased Risk ◽  
Factor Α ◽  
Necrosis Factor

With the aging of the baby-boom generation and increases in life expectancy, the American population is growing older. Aging is associated with adverse changes in glucose tolerance and increased risk of diabetes; the increasing prevalence of diabetes among older adults suggests a clear need for effective diabetes prevention approaches for this population. The purpose of paper is to review what is known about changes in glucose tolerance with advancing age and the potential utility of resistance training (RT) as an intervention to prevent diabetes among middle-aged and older adults. Age-related factors contributing to glucose intolerance, which may be improved with RT, include improvements in insulin signaling defects, reductions in tumor necrosis factor-α, increases in adiponectin and insulin-like growth factor-1 concentrations, and reductions in total and abdominal visceral fat. Current RT recommendations and future areas for investigation are presented.

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