scholarly journals Transgenic Expression of Bmp3b in Mesenchymal Progenitors Mitigates Age-Related Muscle Mass Loss and Neuromuscular Junction Degeneration

2021 ◽  
Vol 22 (19) ◽  
pp. 10246
Author(s):  
Tamaki Kurosawa ◽  
Keitaro Minato ◽  
Madoka Ikemoto-Uezumi ◽  
Jun Hino ◽  
Kunihiro Tsuchida ◽  
...  
Keyword(s):  
Neuromuscular Junctions ◽  
Effective Means ◽  
Specific Gene ◽  
Cross Sectional ◽  
Protective Function ◽  
Transgenic Expression ◽  
Mesenchymal Progenitors ◽  
Age Related ◽  
Muscle Mass Loss ◽  
And Function

Skeletal muscle is a vital organ for a healthy life, but its mass and function decline with aging, resulting in a condition termed sarcopenia. The etiology of sarcopenia remains unclear. We recently demonstrated that interstitial mesenchymal progenitors are essential for homeostatic muscle maintenance, and a diminished expression of the mesenchymal-specific gene Bmp3b is associated with sarcopenia. Here, we assessed the protective function of Bmp3b against sarcopenia by generating conditional transgenic (Tg) mice that enable a forced expression of Bmp3b specifically in mesenchymal progenitors. The mice were grown until they reached the geriatric stage, and the age-related muscle phenotypes were examined. The Tg mice had significantly heavier muscles compared to control mice, and the type IIB myofiber cross-sectional areas were preserved in Tg mice. The composition of the myofiber types did not differ between the genotypes. The Tg mice showed a decreasing trend of fibrosis, but the degree of fat infiltration was as low as that in the control mice. Finally, we observed the preservation of innervated neuromuscular junctions (NMJs) in the Tg muscle in contrast to the control muscle, where the NMJ degeneration was conspicuous. Thus, our results indicate that the transgenic expression of Bmp3b in mesenchymal progenitors alleviates age-related muscle deterioration. Collectively, this study strengthens the beneficial role of mesenchymal Bmp3b against sarcopenia and suggests that preserving the youthfulness of mesenchymal progenitors may be an effective means of combating sarcopenia.

scholarly journals The aging neuromuscular system and motor performance

2016 ◽  
Vol 121 (4) ◽  
pp. 982-995 ◽  
Author(s):  
Sandra K. Hunter ◽  
Hugo M. Pereira ◽  
Kevin G. Keenan
Keyword(s):  
Motor Unit ◽  
Motor Performance ◽  
Neuromuscular Junctions ◽  
Myosin Heavy Chain Isoforms ◽  
Motor Unit Action Potential ◽  
Neuromuscular System ◽  
Cross Sectional ◽  
Very Old ◽  
Age Related ◽  
Age Related Changes

Age-related changes in the basic functional unit of the neuromuscular system, the motor unit, and its neural inputs have a profound effect on motor function, especially among the expanding number of old (older than ∼60 yr) and very old (older than ∼80 yr) adults. This review presents evidence that age-related changes in motor unit morphology and properties lead to impaired motor performance that includes 1) reduced maximal strength and power, slower contractile velocity, and increased fatigability; and 2) increased variability during and between motor tasks, including decreased force steadiness and increased variability of contraction velocity and torque over repeat contractions. The age-related increase in variability of motor performance with aging appears to involve reduced and more variable synaptic inputs that drive motor neuron activation, fewer and larger motor units, less stable neuromuscular junctions, lower and more variable motor unit action potential discharge rates, and smaller and slower skeletal muscle fibers that coexpress different myosin heavy chain isoforms in the muscle of older adults. Physical activity may modify motor unit properties and function in old men and women, although the effects on variability of motor performance are largely unknown. Many studies are of cross-sectional design, so there is a tremendous opportunity to perform high-impact and longitudinal studies along the continuum of aging that determine 1) the influence and cause of the increased variability with aging on functional performance tasks, and 2) whether lifestyle factors such as physical exercise can minimize this age-related variability in motor performance in the rapidly expanding numbers of very old adults.

scholarly journals Telomeres and Age-Related Diseases

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1335
Author(s):  
Hans-Jürgen Gruber ◽  
Maria Donatella Semeraro ◽  
Wilfried Renner ◽  
Markus Herrmann
Keyword(s):  
Telomere Length ◽  
Analytical Techniques ◽  
Telomerase Activity ◽  
Dimensional Structure ◽  
Protective Function ◽  
3 Dimensional ◽  
Age Related ◽  
Telomere Biology ◽  
Linear Chromosomes ◽  
And Function

Telomeres are at the non-coding ends of linear chromosomes. Through a complex 3-dimensional structure, they protect the coding DNA and ensure appropriate separation of chromosomes. Aging is characterized by a progressive shortening of telomeres, which compromises their structure and function. Because of their protective function for genomic DNA, telomeres appear to play an important role in the development and progression of many age-related diseases, such as cardiovascular disease (CVD), malignancies, dementia, and osteoporosis. Despite substantial evidence that links telomere length with these conditions, the nature of these observations remains insufficiently understood. Therefore, future studies should address the question of causality. Furthermore, analytical methods should be further improved with the aim to provide informative and comparable results. This review summarize the actual knowledge of telomere biology and the possible implications of telomere dysfunction for the development and progression of age-related diseases. Furthermore, we provide an overview of analytical techniques for the measurement of telomere length and telomerase activity.

scholarly journals Gut Microbiota, Muscle Mass and Function in Aging: A Focus on Physical Frailty and Sarcopenia

Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1633 ◽  
Author(s):  
Andrea Ticinesi ◽  
Antonio Nouvenne ◽  
Nicoletta Cerundolo ◽  
Pamela Catania ◽  
Beatrice Prati ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Physical Function ◽  
Muscle Mass ◽  
Physical Performance ◽  
Microbiota Composition ◽  
Physical Frailty ◽  
Deficit Accumulation ◽  
Cross Sectional ◽  
Age Related ◽  
And Function

Human gut microbiota is able to influence the host physiology by regulating multiple processes, including nutrient absorption, inflammation, oxidative stress, immune function, and anabolic balance. Aging is associated with reduced microbiota biodiversity, increased inter-individual variability, and over-representation of pathobionts, and these phenomena may have great relevance for skeletal muscle mass and function. For this reason, the presence of a gut-muscle axis regulating the onset and progression of age-related physical frailty and sarcopenia has been recently hypothesized. In this narrative review, we summarize the studies supporting a possible association between gut microbiota-related parameters with measures of muscle mass, muscle function, and physical performance in animal models and humans. Reduced muscle mass has been associated with distinct microbiota composition and reduced fermentative capacity in mice, and the administration of probiotics or butyrate to mouse models of muscle wasting has been associated with improved muscle mass. However, no studies have targeted the human microbiome associated with sarcopenia. Limited evidence from human studies shows an association between microbiota composition, involving key taxa such as Faecalibacterium and Bifidobacterium, and grip strength. Similarly, few studies conducted on patients with parkinsonism showed a trend towards a different microbiota composition in those with reduced gait speed. No studies have assessed the association of fecal microbiota with other measures of physical performance. However, several studies, mainly with a cross-sectional design, suggest an association between microbiota composition and frailty, mostly assessed according to the deficit accumulation model. Namely, frailty was associated with reduced microbiota biodiversity, and lower representation of butyrate-producing bacteria. Therefore, we conclude that the causal link between microbiota and physical fitness is still uncertain due to the lack of targeted studies and the influence of a large number of covariates, including diet, exercise, multimorbidity, and polypharmacy, on both microbiota composition and physical function in older age. However, the relationship between gut microbiota and physical function remains a very promising area of research for the future.

scholarly journals Lynx1 regulates nAChRs to preserve the structure and function of neuromuscular synapses during aging

2020 ◽  
Author(s):  
Sydney V. Doss ◽  
Sébastien Barbat-Artigas ◽  
Tracey Myers ◽  
Bhola Shankar Pradhan ◽  
Tomasz J. Prószyński ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Neuromuscular Junctions ◽  
Structure And Function ◽  
Neuromuscular Synapses ◽  
Adult Mice ◽  
Homeostatic Synaptic Plasticity ◽  
Age Related ◽  
And Function ◽  
The Brain

AbstractNicotinic acetylcholine receptors (nAChRs) undergo aberrant changes in diseases and with advancing age that compromise the structure and function of neuromuscular junctions (NMJs). Despite this recognition, the mechanisms that regulate muscle nAChRs remain poorly understood. Here, we ask if Lynx1, shown to regulate nAChRs in the brain, plays a similar role at NMJs. We show that Lynx1 concentrates in the postsynaptic region of NMJs where it modulates the function and stability of nAChRs in young adult mice. However, Lynx1 levels decrease at aged NMJs suggesting roles in synaptic maintenance. Supporting this possibility, deletion of Lynx1 prematurely and progressively increases the incidence of NMJs with age-related features, culminating in the atrophy of muscle fibers. These data show that by promoting homeostatic synaptic plasticity and NMJ remodeling, Lynx1 regulation of nAChRs mitigates age-related damages at NMJs.

scholarly journals Cross-sectional study on the drug utilization and evaluation indicator of antibiotics used in pediatric population

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xu Hu ◽  
Xueting Zhang ◽  
Yao Wang ◽  
Xuefeng Xie
Keyword(s):  
Anatomical Therapeutic Chemical ◽  
Pediatric Population ◽  
Effective Means ◽  
Drug Dose ◽  
Defined Daily Dose ◽  
Dose Frequency ◽  
Cross Sectional ◽  
Age Related ◽  
Antibiotic Drug ◽  
Daily Dose

Abstract Background The lack of medication standards is a serious problem in paediatrics mainly because of age-related differences in organ development and physiological functions in children. Consequently, dosage measurement becomes inaccurate. For this reason, methods for evaluating and monitoring rational paediatric medications should be developed. Drug use indicators, such as those similar to the drug utilisation index (DUI) based on the Anatomical Therapeutic Chemical/Defined Daily Dose (DDD) and widely used for the assessment of appropriate dosage in adults, should be explored in terms of their applicability to children. Methods A total of 5,538 prescriptions of antibiotics selected from a general teaching hospital were included. Drug, dose, frequency and treatment duration were obtained from each prescription. The prescription daily dose (PDD) of each antibiotic drug was calculated as the average of the daily doses. Underdose and overdose were determined in terms of the PDD/DDD ratio for each prescription. Children’s DUI (cDUI) was explored in terms of the appropriate dosage for children as follows: the meaning of children’s DDD (cDDD) and the evaluation of paediatric drug dosage. Results The top five antibiotics and their utilisation rates were as follows: cefmetazole sodium injection (18.47 %), erythromycin lactobionate injection (15.07 %), amoxicillin/clavulanate potassium injection (10.72 %), ceftriaxone sodium injection (9.50 %) and azithromycin dry suspension (8.02 %). The ratio of cDUI and PDD/cDDD was mostly not close to 1. Conclusions The establishment of a cDUI system is an effective means of paediatric dosage evaluation. In addition to DDDs, cDUI and PDD/cDDD should be used to analyse the utilisation of antibiotics in children.

scholarly journals Prolonged Immobilization Exacerbates the Loss of Muscle Mass and Function Induced by Cancer-Associated Cachexia through Enhanced Proteolysis in Mice

2020 ◽  
Vol 21 (21) ◽  
pp. 8167
Author(s):  
Laura Mañas-García ◽  
Antonio Penedo-Vázquez ◽  
Adrián López-Postigo ◽  
Jorieke Deschrevel ◽  
Xavier Durán ◽  
...  
Keyword(s):  
Muscle Damage ◽  
Muscle Mass ◽  
Muscle Regeneration ◽  
Troponin I ◽  
Hindlimb Unloading ◽  
Cross Sectional ◽  
Muscle Mass Loss ◽  
Prolonged Immobilization ◽  
And Function ◽  
Fast Twitch

We hypothesized that in mice with lung cancer (LC)-induced cachexia, periods of immobilization of the hindlimb (7 and 15 days) may further aggravate the process of muscle mass loss and function. Mice were divided into seven groups (n = 10/group): (1) non-immobilized control mice, (2) 7-day unloaded mice (7-day I), (3) 15-day unloaded mice (15-day I), (4) 21-day LC-cachexia group (LC 21-days), (5) 30-day LC-cachexia group (LC 30-days), (6) 21-day LC-cachexia group besides 7 days of unloading (LC 21-days + 7-day I), (7) 30-day LC-cachexia group besides 15 days of unloading (LC 30-days + 15-day I). Physiological parameters, body weight, muscle and tumor weights, phenotype and morphometry, muscle damage (including troponin I), proteolytic and autophagy markers, and muscle regeneration markers were identified in gastrocnemius muscle. In LC-induced cachexia mice exposed to hindlimb unloading, gastrocnemius weight, limb strength, fast-twitch myofiber cross-sectional area, and muscle regeneration markers significantly decreased, while tumor weight and area, muscle damage (troponin), and proteolytic and autophagy markers increased. In gastrocnemius of cancer-cachectic mice exposed to unloading, severe muscle atrophy and impaired function was observed along with increased muscle proteolysis and autophagy, muscle damage, and impaired muscle regeneration.

Mouse heart valve structure and function: echocardiographic and morphometric analyses from the fetus through the aged adult

2008 ◽  
Vol 294 (6) ◽  
pp. H2480-H2488 ◽  
Author(s):  
Robert B. Hinton ◽  
Christina M. Alfieri ◽  
Sandra A. Witt ◽  
Betty J. Glascock ◽  
Philip R. Khoury ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Normal Mouse ◽  
Structure And Function ◽  
Mouse Heart ◽  
Morphometric Data ◽  
Cross Sectional ◽  
Age Related ◽  
Morphometric Analyses ◽  
Valve Structure ◽  
And Function

The purpose of this study is to provide standard echocardiographic and morphometric data for normal mouse valve structure and function from late fetal to aged adult stages. Cross-sectional, two-dimensional and Doppler transthoracic echocardiography was performed in C57BL6 mice anesthetized with 1% to 2% isoflurane at embryonic day 18.5 (late fetal), 10 days (neonate), 1 mo (juvenile), 2 mo (young adult), 9 mo (old adult), and 16 mo (aged adult). Normal annulus dimensions indexed to age or weight, and selected flow velocities, were established by echocardiography. After echocardiographic imaging, hearts were harvested and histological and morphometric analyses were performed. Morphometric analysis demonstrated a progressive valve thinning and elongation during the fetal and juvenile stages that plateaued during adult stages (ANOVA, P < 0.01); however, there was increased thickening of the hinge of the aortic valve with advanced age, reminiscent of human aortic valve sclerosis. There was no age-related calcification. The results of this study provide comprehensive echocardiographic and morphometric data for normal mouse valve structure and function from late fetal to aged adult stages and should prove useful as a reference standard for future studies using mouse models of progressive valve disease.

Age related volume of cadaver-prostates in Bangladesh

1970 ◽  
Vol 4 (2) ◽  
pp. 74-77
Author(s):  
Rukshana Ahmed ◽  
Shamim Ara
Keyword(s):  
Prostate Gland ◽  
Age Groups ◽  
Clinical Settings ◽  
Cross Sectional ◽  
Medical College ◽  
Age Related ◽  
Group A ◽  
Key Words Prostate ◽  
The Mean ◽  
Group B

Pathological changes in the prostate gland occur commonly with advancing age including inflammation, atrophy, hyperplasia and carcinoma and a change in volume is also evident. Estimation of volume of prostate may be useful in a variety of clinical settings. A cross-sectional descriptive study was designed to see the changes in volume of the prostate with advancing age and done in the Department of Anatomy, Dhaka Medical College, Dhaka from August 2006 to June 2007. The study was performed on 70 post-mortem human prostates collected from the unclaimed dead bodies that were under examination in the Department of Forensic Medicine, Dhaka Medical College, Dhaka. The samples were divided into three age groups; group A (10-20 years), group B (21-40 years) and group C (41-70 years). Volume of the sample was measured by using the ellipsoid formula. The mean ± SD volume of prostate was 7.68 ± 3.64 cm3 in group A, 10.61 ± 3.99 cm3 in group B and 15.40 ± 6.31 cm3 in group C. Mean difference in volume between group A and group C, group B and group C were statistically significant (p<0.001). Statistically significant positive correlation was found between age and volume of prostate (r = + 0.579, p < 0.001). Key Words: Prostate; volume; Bangladeshi. DOI: 10.3329/imcj.v4i2.6501Ibrahim Med. Coll. J. 2010; 4(2): 74-77

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