Age-related Structural Changes Research Articles

Telomere length and brain aging: A systematic review and meta-analysis.

The current evidence on the association of leukocyte telomere length (LTL) with age-related structural and cognitive changes in the brain is mixed. Herein conforming to PRISMA 2020 guidelines, we performed a systematic review and meta-analysis using data from 27 observational studies in non-demented individuals. We used effect size and p-value based meta-analysis methods considering marked heterogeneity among studies. We found that the longer LTL was associated with higher brain volume (β=0.43, 95%CI: 0.36-0.50%, p=0.008, N=1102) and with higher global cognition (β=0.01; 95%CI: 0.00-0.02, p=0.03, N=19609) by effect size based meta-analysis and with brain volume, hippocampal volume, global cognition, cognitive domains of attention/speed as well as executive functions by p-value based meta-analysis. No significant association of LTL with brain white matter hyperintensities was detected. Furthermore, the evidence strongly suggests a subgroup-specific canonical effect of telomeres, notably in older individuals and females. In conclusion, we provide meta-analytic evidence on the beneficial effect of telomeres on brain structure as well as cognition and advocate for a beneficial subgroup-specific effect that warrants further attention.

Predicting demographic characteristics from anterior segment OCT images with deep learning: A study protocol.

IntroductionAnterior segment optical coherence tomography (AS-OCT) is a non-contact, rapid, and high-resolution in vivo modality for imaging of the eyeball’s anterior segment structures. Because progressive anterior segment deformation is a hallmark of certain eye diseases such as angle-closure glaucoma, identification of AS-OCT structural changes over time is fundamental to their diagnosis and monitoring. Detection of pathologic damage, however, relies on the ability to differentiate it from normal, age-related structural changes.Methods and analysisThis proposed large-scale, retrospective cross-sectional study will determine whether demographic characteristics including age can be predicted from deep learning analysis of AS-OCT images; it will also assess the importance of specific anterior segment areas of the eyeball to the prediction. We plan to extract, from SUPREME®, a clinical data warehouse (CDW) of Seoul National University Hospital (SNUH; Seoul, South Korea), a list of patients (at least 2,000) who underwent AS-OCT imaging between 2008 and 2020. AS-OCT images as well as demographic characteristics including age, gender, height, weight and body mass index (BMI) will be collected from electronic medical records (EMRs). The dataset of horizontal AS-OCT images will be split into training (80%), validation (10%), and test (10%) datasets, and a Vision Transformer (ViT) model will be built to predict demographics. Gradient-weighted Class Activation Mapping (Grad-CAM) will be used to visualize the regions of AS-OCT images that contributed to the model’s decisions. The accuracy, sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve (AUC) will be applied to evaluate the model performance.ConclusionThis paper presents a study protocol for prediction of demographic characteristics from AS-OCT images of the eyeball using a deep learning model. The results of this study will aid clinicians in understanding and identifying age-related structural changes and other demographics-based structural differences.Trial registrationRegistration ID with open science framework: 10.17605/OSF.IO/FQ46X.

P85. Sex Differences in Regional Patterns of Brain-Age-Gap Estimates

Neuroimaging studies have been instrumental in identifying sex-differences in brain structure, and there is robust evidence for age-related changes in brain structure throughout the lifespan. However, the literature on sex-differences in regional patterns of age-related changes in young adulthood remains limited. To address this, we availed of a machine learning model to obtain local brain-age-gap estimates (L-brainAGE), which reflect voxel-wise differences between an individual’s chronological and biological brain age.

Association of Age and Structural Brain Changes With Functional Connectivity and Executive Function in a Middle-Aged to Older Population-Based Cohort.

Aging is accompanied by structural brain changes that are thought to underlie cognitive decline and dementia. Yet little is known regarding the association between increasing age, structural brain damage, and alterations of functional brain connectivity. The aim of this study was to evaluate whether cortical thickness and white matter damage as markers of age-related structural brain changes are associated with alterations in functional connectivity in non-demented healthy middle-aged to older adults. Therefore, we reconstructed functional connectomes from resting-state functional magnetic resonance imaging (MRI) (rsfMRI) data of 976 subjects from the Hamburg City Health Study, a prospective population-based study including participants aged 45–74 years from the metropolitan region Hamburg, Germany. We performed multiple linear regressions to examine the association of age, cortical thickness, and white matter damage quantified by the peak width of skeletonized mean diffusivity (PSMD) from diffusion tensor imaging on whole-brain network connectivity and four predefined resting state networks (default mode, dorsal, salience, and control network). In a second step, we extracted subnetworks with age-related decreased functional connectivity from these networks and conducted a mediation analysis to test whether the effect of age on these networks is mediated by decreased cortical thickness or PSMD. We observed an independent association of higher age with decreased functional connectivity, while there was no significant association of functional connectivity with cortical thickness or PSMD. Mediation analysis identified cortical thickness as a partial mediator between age and default subnetwork connectivity and functional connectivity within the default subnetwork as a partial mediator between age and executive cognitive function. These results indicate that, on a global scale, functional connectivity is not determined by structural damage in healthy middle-aged to older adults. There is a weak association of higher age with decreased functional connectivity which, for specific subnetworks, appears to be mediated by cortical thickness.

Morphometric aspects of studying the features of age structural reconstruction of the walls of the prostate arteries

Summary. Age structural changes in the organ artery to date are the subject of study for morphologists and clinicians. At the same time, the age features of remodeling of the prostate arteries remain poorly understood. The aim of the study – morphometric study of the features of age structural reconstruction of the prostate artery wall. Materials and Methods. Morphometrically studied the structural age reconstruction of the prostate artery wall of 45 white rats, which were divided into 2 groups. Group 1 consisted of 15 animals aged 6 months, group 2 – 30 rats aged 24 months. Euthanasia of animals was performed by bloodletting under conditions of thiopental anesthesia. Histological micropreparations were made from the prostate gland, which morphometrically determined the outer and inner diameters, intima thicknesses, media, adventitia, intimo-medial, intimo-adventitia, adventitial-medial indices of arteries of small and medium calibers, relative volumes of damage endotheliocytes. Quantitative morphological parameters were processed statistically. Results. The age structural reorganization of the arterial walls of the prostate gland, which was characterized by an increase in the thickness of the media, adventitia, atrophy of the intima, violation of the relationship between their morphometric parameters, increasing the number of damaged endothelial cells. The detected structural changes dominated in the arteries of small caliber of the studied organ, which play a major role in ensuring blood supply to the studied organ. The increase in the relative volume of damaged endothelial cells in the arterial bed of the prostate in laboratory white male rats was mainly due to apoptotically altered endotheliocytes, the number of which increases with age. Conclusions. With age, morphological changes in the walls of the prostate arteries of laboratory adult white male rats are characterized by their thickening, narrowing of the lumen, atrophic processes in the intima, increasing thickness of the media and adventitia, disruption of relations between them, increasing the relative volume of damaged endoteliocytes. The severity of age-related structural changes in the walls of the arterial bed of the prostate dominates in the arteries of small caliber

Withdrawal Notice: A New Perspective on the Treatment of Alzheimer's disease and Sleep Deprivation-related Consequences: Curcumin

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Accumulation of systematic TPM1 mediates inflammation and neuronal remodeling by phosphorylating PKA and regulating the FABP5/NF-κB signaling pathway in the retina of aged mice.

The molecular mechanisms underlying functional decline during normal brain aging are poorly understood. Here, we identified the actin‐associated protein tropomyosin 1 (TPM1) as a new systemic pro‐aging factor associated with function deficits in normal aging retinas. Heterochronic parabiosis and blood plasma treatment confirmed that systemic factors regulated age‐related inflammatory responses and the ectopic dendritic sprouting of rod bipolar (RBC) and horizontal (HC) cells in the aging retina. Proteomic analysis revealed that TPM1 was a potential systemic molecule underlying structural and functional deficits in the aging retina. Recombinant TPM1 protein administration accelerated the activation of glial cells, the dendritic sprouting of RBCs and HCs and functional decline in the retina of young mice, whereas anti‐TPM1 neutralizing antibody treatment ameliorated age‐related structural and function changes in the retina of aged mice. Old mouse plasma (OMP) induced glial cell activation and the dendritic outgrowth of RBCs and HCs in young mice, and yet TMP1‐depleted OMP failed to reproduce the similar effect in young mice. These results confirmed that TPM1 was a systemic pro‐aging factor. Moreover, we demonstrated that systematic TPM1 was an immune‐related molecule, which elicited endogenous TPM1 expression and inflammation by phosphorylating PKA and regulating FABP5/NF‐κB signaling pathway in normal aging retinas. Interestingly, we observed TPM1 upregulation and the ectopic dendritic sprouting of RBCs and HCs in young mouse models of Alzheimer's disease, indicating a potential role of TPM1 in age‐related neurodegenerative diseases. Our data indicate that TPM1 could be targeted for combating the aging process.

A deep ensemble hippocampal CNN model for brain age estimation applied to Alzheimer’s diagnosis

Age-associated diseases rise as life expectancy increases. The brain presents age-related structural changes across life, with different extends between subjects and groups. During the development of neurodegenerative diseases, these changes are more intense and accentuated. As Alzheimer’s disease (AD) develops, the brain reflects accelerated aging with minor extends associated with mild cognitive impairment (MCI), i.e., the prodromal stage of AD. Therefore, it is crucial to understand a healthy brain aging process to predict a cognitive decline. This study produced an efficient age estimation framework using only the hippocampal regions that explores the associations of the brain age prediction error of age-matched cognitively normal (CN) subjects with AD and MCI subjects. For this, we have developed two convolutional neural networks. The first achieved very competitive state-of-the-art metrics, i.e., mean absolute error (MAE) of 3.31 and root mean square error (RMSE) of 4.65. The second has also achieved competitive metrics, but more importantly, we founded a statistically significant analysis of our delta estimation error between the compared groups. Further, we correlated our results with clinical measurements, e.g., Mini-Mental State Examination (MMSE) score, and obtained a significant negative correlation. In addition, we compared our results with other published studies. Therefore, our findings suggest that our delta could become a biomarker to support AD and MCI diagnosis.

Comparative morphometric analysis of age-related changes in the pyramidal neurons of the human prefrontal and posterior associative cortex from birth to 7 years

Aim: This article is devoted to the study of age-related changes in the body volume of pyramidal neurons (VP) of the human prefrontal (PFC) and posterior associative cortex (PAC) in children from birth to 7 years of age. Methods: The material consisted of left cerebral hemispheres obtained from 60 male individuals. We studied the areas 8, 45 and 10 in the PFC and area 37 in subareas 37ac, 37a, 37d in the PAC. For morphometry of pyramidal neurons in cortical sublayer III3, we used virtual images of serial frontal paraffin sections of cortex 10 thick stained by Nissl. We determined the mean value of VP (mean VP), the standard error of the mean, and the confidence interval for each age group. Results: The most significant changes in the mean VP in all studied cortical areas occurred during the first 6 months of life. The greatest increase in the VP was detected in the PFC from 3.5 to 7 years, and in the PAC from 1.5 to 3 years of age. There are close positive correlations between agerelated changes in the size of neurons in the PFC and in the PAC. Conclusion: In children, the development of pyramidal neurons of the external pyramidal plate in the PAC occurs earlier and at a more intensive pace compared to the PFC. We suggest that VP is an important quantitative indicator that allows us to assess the timing and rate of age-related structural changes in the cerebral cortex.

A New Perspective on the Treatment of Alzheimer's Disease and Sleep Deprivation-Related Consequences: Can Curcumin Help?

Sleep disturbances, as well as sleep-wake rhythm disorders, are characteristic symptoms of Alzheimer's disease (AD) that may head the other clinical signs of this neurodegenerative disease. Age-related structural and physiological changes in the brain lead to changes in sleep patterns. Conditions such as AD affect the cerebral cortex, basal forebrain, locus coeruleus, and the hypothalamus, thus changing the sleep-wake cycle. Sleep disorders likewise adversely affect the course of the disease. Since the sleep quality is important for the proper functioning of the memory, impaired sleep is associated with problems in the related areas of the brain that play a key role in learning and memory functions. In addition to synthetic drugs, utilization of medicinal plants has become popular in the treatment of neurological diseases. Curcuminoids, which are in a diarylheptanoid structure, are the main components of turmeric. Amongst them, curcumin has multiple applications in treatment regimens of various diseases such as cardiovascular diseases, obesity, cancer, inflammatory diseases, and aging. Besides, curcumin has been reported to be effective in different types of neurodegenerative diseases. Scientific studies exclusively showed that curcumin leads significant improvements in the pathological process of AD. Yet, its low solubility hence low bioavailability is the main therapeutic limitation of curcumin. Although previous studies have focused different types of advanced nanoformulations of curcumin, new approaches are needed to solve the solubility problem. This review summarizes the available scientific data, as reported by the most recent studies describing the utilization of curcumin in the treatment of AD and sleep deprivation-related consequences.

Age-related structural changes show that loss of fibers is not a significant contributor to muscle atrophy in old mice.

Age-related loss of skeletal muscle mass is widely considered a consequence of both fiber atrophy and fiber death. Evidence for fiber death derives largely from an age-related reduction in fiber numbers in muscle cross-sections, however it is unclear how age-related alterations in muscle morphology affect accuracy of such counts. To explore this we performed an examination of muscle and tendon length, muscle mass and girth, and pennation angle, in addition to histological section fiber counts of parallel-fibered (sternomastoid), fusiform (biceps brachii), and pennate (tibialis anterior, extensor digitorum longus, soleus) muscles from 31 mice aged 6-32months. Age-related decline in mass and girth occurred in soleus (p=0.026; p=0.040), tibialis anterior (p=0.004; p=0.039), and extensor digitorum longus (p=0.040; p=0.022) muscles, for which location of maximal girth also changed. Tendon length and pennation angle remained consistent across the lifespan in all except soleus which showed elongation of both proximal and distal tendons coupled with alterations in pennation angle. Age-related decreases in fiber number were observed in transversely sectioned soleus and extensor digitorum longus muscles however when age-related changes in morphology were accounted for via oblique sectioning the age-related decrease in fiber number was eliminated. Findings show loss of fibers is not a significant contributor to age-related muscle wasting in mice, and that age-related changes in connective tissue selectively impact muscle structure. Fiber shortening is a likely contributor to loss of mass and change in function in muscles of old mice.

Quantity versus quality: Age-related differences in muscle volume, intramuscular fat, and mechanical properties in the triceps surae.

With aging comes reductions in the quality and size of skeletal muscle. These changes influence the force-generating capacity of skeletal muscle and contribute to movement deficits that accompany aging. Although declines in strength remain a significant barrier to mobility in older adults, the association between age-related changes in muscle structure and function remain unresolved. In this study, we compared age-related differences in (i) muscle volume and architecture, (ii) the quantity and distribution of intramuscular fat, and (iii) muscle shear modulus (an index of stiffness) in the triceps surae in 21 younger (24.6±4.3years) and 15 older (70.4±2.4years) healthy adults. Additionally, we explored the relationship between muscle volume, architecture, intramuscular fat and ankle plantar flexion strength in young and older adults. Magnetic resonance imaging was used to determine muscle volume and intramuscular fat content. B-mode ultrasound was used to quantify muscle architecture, shear-wave elastography was used to measure shear modulus, and ankle strength was measured during maximal isometric plantar flexion contractions. We found that older adults displayed higher levels of intramuscular fat yet similar muscle volumes in the medial (MG) and lateral gastrocnemius (LG) and soleus, compared to younger adults. These age-related higher levels of intramuscular fat were associated with lower muscle shear modulus in the LG and MG. We also found that muscle physiological cross-sectional area (PCSA) that accounted for age-associated differences in intramuscular fat showed a modest increase in its association with ankle strength compared to PCSA that did not account for fat content. This highlights that skeletal muscle fat infiltration plays a role in age-related strength deficits, but does not fully explain the age-related loss in muscle strength, suggesting that other factors play a more significant role.

Neural Presbyacusis in Humans Inferred from Age-Related Differences in Auditory Nerve Function and Structure.

A common complaint of older adults is difficulty understanding speech, particularly in challenging listening conditions. Accumulating evidence suggests that these difficulties may reflect a loss and/or dysfunction of auditory nerve (AN) fibers. We used a novel approach to study age-related changes in AN structure and several measures of AN function, including neural synchrony, in 58 older adults and 42 younger adults. AN activity was measured in response to an auditory click (compound action potential; CAP), presented at stimulus levels ranging from 70 to 110 dB pSPL. Poorer AN function was observed for older than younger adults across CAP measures at higher but not lower stimulus levels. Associations across metrics and stimulus levels were consistent with age-related AN disengagement and AN dyssynchrony. High-resolution T2-weighted structural imaging revealed age-related differences in the density of cranial nerve VIII, with lower density in older adults with poorer neural synchrony. Individual differences in neural synchrony were the strongest predictor of speech recognition, such that poorer synchrony predicted poorer recognition of time-compressed speech and poorer speech recognition in noise for both younger and older adults. These results have broad clinical implications and are consistent with an interpretation that age-related atrophy at the level of the AN contributes to poorer neural synchrony and may explain some of the perceptual difficulties of older adults.SIGNIFICANCE STATEMENT Differences in auditory nerve (AN) pathophysiology may contribute to the large variations in hearing and communication abilities of older adults. However, current diagnostics focus largely on the increase in detection thresholds, which is likely because of the absence of indirect measures of AN function in standard clinical test batteries. Using novel metrics of AN function, combined with estimates of AN structure and auditory function, we identified age-related differences across measures that we interpret to represent age-related reductions in AN engagement and poorer neural synchrony. Structure-function associations are consistent with an explanation of AN deficits that arise from age-related atrophy of the AN. Associations between neural synchrony and speech recognition suggest that individual and age-related deficits in neural synchrony contribute to speech recognition deficits.

The effect of aging on inter-limb coordination: Establishing a novel transcranial alternating current stimulation (tACS) protocol by means of electroencephalography (EEG)

Abstract Healthy aging is a societal challenge with a significant socioeconomic impact. Gaining knowledge about neurodegenerative changes that impact functional independence is thus of high scientific importance. Age-related structural and functional neural changes have consequences for inter-limb coordination, which forms an intrinsic part of everyday life (e.g., driving, buttoning a shirt). Research has demonstrated that transcranial alternating current stimulation (tACS) targeting neural oscillations can alter behavioral performance. Nevertheless, profound understanding of tACS in the context of inter-limb coordination is yet to be achieved. In order to accomplish this, a more thorough understanding of the neural oscillations underlying inter-limb coordination is of utmost importance. The current study used electroencephalography (EEG) in healthy right-handed participants during two inter-limb coordination tasks; the bimanual tracking task (BTT) and the multi-limb reaction time task (MLT). The BTT consists of rotating two dials with both hands in a coordinated fashion. Three conditions were used, differing in left- and right-hand movement frequency. The MLT requires participants to lift multiple limbs in a correct manner. Six conditions were used, differing in required motor response (e.g., lifting right arm and left leg, lifting left arm and both legs). Twenty healthy right-handed young adults (age: 22.3 ± 1.0 (mean ± standard deviation)) and nineteen older adults (age: 70.7 ± 3.0) participated. Laplacian filtered EEG data will be analyzed in the time-frequency domain using morlet wavelet convolution. EEG time-frequency data between 4 and 35 hertz will be analyzed by means of repeated measures ANOVA, investigating differences across conditions and groups for each task respectively. In addition, bivariate channel-level functional connectivity will be analyzed using inter-site phase clustering. Behavioral data will be analyzed with a mixed model approach. These insights will be used to establish novel tACS protocols. If significant differences between young and older adults are present, these findings can lead to age-adapted tACS protocols. Keywords: Electroencephalography, Transcranial alternating current stimulation, Ageing, Functional connectivity

Comparative Study on the Effect of Adipose tissue derived Mesenchymal Stem Cells versus Metformin on Age-related Structural Changes of the Cerebellum in Albino Rat

Abstract Introduction Aging is a normal physiological process that affects all organs in the body including the cerebellum. Metformin is an anti-diabetic drug that is used in some age-related diseases. Regenerative medicine using adipose tissue derived mesenchymal stem cells (ADMSCs) is an emerging promising strategy. Aim to compare between the role of ADMSCs and metformin on the age-related structural changes of the cerebellum in female albino rats. Materials and methods Fifty-five female rats of different ages (4, 12 and 24 months) were included in this study. They were divided into three groups according to their ages: Group I (Adult rats), Group II (Old rats) and Group III (Senile rats). Group II and Group III were subdivided into three subgroups, Subgroup a: rats were left without treatment, Subgroup b: rats were given a single dose of 1X106 ADMSCs via tail vein. Subgroup c: Rats received300 mg/kg metformin/day orally. Rats were sacrificed after four weeks. The cerebellum was collected and processed for H&E, Toluidine blue and immuno-histochemical reaction using glial fibrillary acidic protein (GFAP). Results Histological examination of the cerebellum of the subgroups IIa and IIIa revealed age-related structural changes in comparison to group I. Purkinje cells appeared distorted with irregular outline. Some Purkinje cells were seen shrunken while others appeared ballooned. Focal loss of Purkinje cells was also noticed. Granular layer contained small widely separated granule cells. GFAP reaction revealed an apparent decrease in number of astrocytes and their processes. The structural changes were more obvious in subgroup IIIa. In ADMSCs treated subgroups (IIbandIIIb); more noticeable improvement of these changes was noticed compared to the corresponding metformin treated subgroups (IIc and IIIc). Conclusion ADMSCs was more effective than metformin in preventing some age-related structural changes of the cerebellum.

The alkaloid centcyamine increases expression of klotho and lamin B1, slowing the onset of skin ageing in vitro and in vivo.

Klotho is a protein known for its beneficial effects on longevity. Centcyamine is an alkaloid present in certain plants whose extracts have an anti-inflammatory effect. Skin fibroblasts are essential to the formation and structure of the dermis. Centcyamine is an indole-based alkaloid composed of coumaric acid, a resveratrol precursor and methoxytryptamine, which can be both a precursor, or a derivative, of melatonin. Given these building blocks and their well-known bioactivities, it was of interest to explore the potential benefits of using this aryl-alkaloid, in cosmetic skincare applications. We tested cultured normal human dermal fibroblasts (NHDF) in vitro to observe how supplementation with centcyamine improves properties of the cells to counteract the effect of ageing. The expression of genes and proteins of interest was quantified. The effect on doubling time and cell function was evaluated following treatment of the cells over several replication cycles. Skin firmness, red spot index and skin isotropy were measured with Dynaskin® , Visia® and Primos® equipment, respectively, and compared over two months in a vehicle-controlled clinical trial on 60 persons. Centcyamine activates the expression of the gene KL and the related protein Klotho in dermal fibroblasts. Moreover, centcyamine slows the replicative ageing process of fibroblasts in culture. These cells retain cellular functions identical to those of young cells: the synthesis of lamin B1, a crucial regulatory protein of proliferation, as well as of collagen I and elastin is retained in aged cells. The clinical data are shown to improve skin isotropy in a majority of subjects, to reduce the red spot intensity and to maintain skin firmness in the treated group vs. the vehicle. The alkaloid centcyamine induces changes in the metabolism of the ageing process of human dermal fibroblasts. The up-to-now unobserved implication of both Klotho and lamin B1 to maintain homeostasis of the skin opens new venues for the prevention of age-related changes in skin structure. The in vitro and clinical data, while not demonstrated to be causally related, converge towards a common goal of skin repair and slower ageing processes.

Presbylarynx, Functional Voice Disorders, Muscle Tension Dysphonia

Presbylarynx refers to age-related structural changes of the vocal folds that include muscle atrophy, reduced neuromuscular control, loss of superficial lamina propria layer, and reduced pliability. The changes result in thin and bowed vocal folds, increased vocal effort requirements, breathy voice, change in habitual pitch, and strain. The primary treatment options are voice therapy focused on strengthening breath support and the intrinsic muscles of the larynx, and optimization of resonance; injection augmentation of the vocal folds; and type I thyroplasty. Functional dysphonia is defined as change in voice quality in the absence of structural or neurological abnormalities of the larynx. Muscle tension dysphonia (MTD) is a subtype of functional voice disorders and involves laryngeal muscle tension imbalance due to excessive or dysregulated activation resulting often in strained or breathy voice. MTD can be divided into primary (psychological etiology or vocal misuse) and secondary (compensatory for organic laryngeal pathology). The mainstay of treatment for MTD is voice therapy, along with medical or surgical treatment of the underlying vocal pathology in secondary MTD. Mutational falsetto, or puberphonia, is a functional voice disorder where a high-pitched, pre-adolescent voice fails to transition to the lower pitch of adulthood. This review contains 5 figures, 7 tables, 4 videos and 10 references Key Words: Presbylarynx, Injection augmentation, Type I thyroplasty, Primary muscle tension dysphonia, Secondary muscle tension dysphonia, Muscle tension patterns, Manual circumlaryngeal therapy, Functional dysphonia, Mutational falsetto

Abstract P440: Cardiac Tissue Chip Model Provides A Platform For Studying Age-related Cardiovascular Complications By Recapitulating Important Hallmarks Of Senescence And Myocardial Ischemia

Introduction: With the rise in the elderly population, there has been an exponential growth in cardiovascular diseases and age-related complications. This necessitates a platform for studying cardiovascular disease in the context of aging. Hypothesis: An engineered cardiac tissue model that can recapitulate critical aspects of aging can be used to study age-related diseases of the cardiovascular system. Methods: Senescence was induced in rat cardiomyoblasts using an acute low-dose doxorubicin treatment. The presence of important senescent markers in the cells like enlarged and flattened nuclei, increased ROS activity, elevated p53 production, DNA damage response foci, and increased expression of cell cycle inhibitor p16 INK4a was evaluated. These senescent cells were then used to engineer cardiac tissue, which was subjected to hemodynamic stresses associated with the pressure-volume changes in the heart. Myocardial ischemia was imposed in the aging cardiac tissue model using hypoxic treatment. Results: Under normal hemodynamic loading, the engineered cardiac tissue retained its cardiac cell characteristics and showed cell alignment along with age-related changes in structure and gene expression. The myocardial ischemic model of the tissue revealed major pathological hallmarks of the disease like increased cell death and natriuretic peptide expression. Conclusion: Our model and methodology provide an effective platform for studying the cardiovascular disease pathologies associated with aging and screening drugs against age-related complications.

Inter-linkage between the health status and socio-economic life of Indian Elderly: An exploration based on 71st Round of NSS data

Like many other countries in the world, India is also in the process of major age-related structural changes with an acceleration of growth in its elderly populations. The present study focused on economic independence andliving arrangements and about how such factors shape perceived health status among the elderly. On the basis of the unit level data from the NSS 71 st Round taken for the 18 major Indian states, an attempt was made in this analysis to establish the inter-linkage between the perceived health status and the financial self-dependence along with aspects of filial status and the factor of co-residence. “Self-reported health status” has been used as a response variable in the present study. The perception of “Poor” health status was significantly reported more by the economically dependent elderly as compared to their independent counterparts, irrespective of their place of residence. The study found that when the elderly are co-residing with their spouse, psychologically they remain more satisfied and on such occasions fifty percent or more of them expressed their health status to be either excellent or good. It has also been empirically found that whenever the elderly lack financial autonomy, they are increasingly found to reveal poor health status may be because of feeling mentally distressed and are having low self-esteem.

Age-dependent mechanical and microstructural properties of the rabbit soleus muscle

During growth there are serious changes in the skeletal muscles to compensate for the changed requirements in terms of body weight and size. In this study, the age-dependent (between 21 and 100 days) mechanical and microstructural properties of rabbit soleus muscle tissue were investigated. For this purpose, morphological properties (animal mass, soleus muscle mass, tibial length) were measured at 5 different times during aging. On the other hand, fibre orientation-dependent axial and semi-confined compression experiments were realised. In addition, the essential components (muscle fibres, extracellular matrix, remaining components), dominating the microstructure of muscle tissue, were analysed. While the mechanical results show hardly any age-dependent differences, the morphological and microstructural results show clear age-dependent differences. All morphological parameters increase significantly (animal mass by 839.2%, muscle mass 1050.6%, tibial length 233.6%). In contrast, microstructural parameters change differently. The percentage of fibres (divided into slow-twitch (ST) and fast-twitch (FT) fibres) increases significantly (137.6%), while the proportions of the extracellular matrix and the remaining components (48.2% and 46.1%) decrease. At the same time, the cross-sectional area of the fibres increases significantly (697.9%). The totality of this age-dependent information provides a deeper understanding of age-related changes in muscle structure and function and may contribute to successful development and validation of growth models in the future. Statement of significanceThis article reports the first comprehensive data set on age-dependent morphological (animal mass, soleus muscle mass, tibial length), mechanical (axial and semi-confined compression), and microstructural (muscle fibres, extracellular matrix, remaining components) properties of the rabbit soleus muscle. On the one hand, the results of this study contribute to the understanding of muscle mechanics and thus to understanding of load transfer mechanisms inside the muscle tissue during growth. On the other hand, these results are relevant to the fields of constitutive formulation of age-dependent muscle tissue.