Effect of aging on the recovery following contraction-induced injury in muscles of female mice

2006 ◽  
Vol 101 (3) ◽  
pp. 887-892 ◽  
Author(s):  
Erik P. Rader ◽  
John A. Faulkner

By the age of 80 yr, the skeletal muscles of men and women decrease in mass and maximum force by ∼30%. Severe contraction-induced injury may contribute to these age-related declines. One to two months after a 225 lengthening contraction protocol (LCP), muscles of young/adult male mice recovered completely, whereas those of old male mice sustained deficits of ∼15% in mass and ∼25% in maximum force. Although gender-related differences in the early events of contraction-induced injury have been reported, the recovery phase of muscles in old female animals has not been investigated. The hypothesis tested was that 2 mo after a severe LCP to the plantar flexor muscle group, the magnitude of recovery of mass and force for old female mice is less than that for adult female mice. The LCP was administered to muscles of adult and old, female C57BL/6 mice. At 3 days, 1 mo, and 2 mo following the LCP, maximum isometric force was measured, and muscles were removed and weighed. Two months following the LCP, the muscles of adult female mice recovered mass and force. In contrast, for old female mice, even after 2 mo, muscle masses were decreased by 11% and maximum forces by 38%. We conclude that, as reported previously for old male mice, a severe contraction-induced injury to muscles of old female mice results in prolonged deficits in mass and force.

2018 ◽  
Vol 75 (6) ◽  
pp. 1042-1049
Author(s):  
Seongjoon Park ◽  
Erkhembayar Nayantai ◽  
Toshimitsu Komatsu ◽  
Hiroko Hayashi ◽  
Ryoichi Mori ◽  
...  

Abstract The orexigenic hormone neuropeptide Y (NPY) plays a pivotal role in the peripheral regulation of fat metabolism. However, the mechanisms underlying the effects of sex on NPY function have not been extensively analyzed. In this study, we examined the effects of NPY deficiency on fat metabolism in male and female mice. Body weight was slightly decreased, whereas white adipose tissue (WAT) mass was significantly decreased as the thermogenic program was upregulated in NPY-/- female mice compared with that in wild-type mice; these factors were not altered in response to NPY deficiency in male mice. Moreover, lack of NPY resulted in an increase in luteinizing hormone (LH) expression in the pituitary gland, with concomitant activation of the estradiol-mediated thermogenic program in inguinal WAT, and alleviated age-related modification of adiposity in female mice. Taken together, these data revealed a novel intracellular mechanism of NPY in the regulation of fat metabolism and highlighted the sexual dimorphism of NPY as a promising target for drug development to reduce postmenopausal adiposity.


2021 ◽  
Vol 11 ◽  
Author(s):  
Anca Hermenean ◽  
Maria Consiglia Trotta ◽  
Sami Gharbia ◽  
Andrei Gelu Hermenean ◽  
Victor Eduard Peteu ◽  
...  

Age and gender are two important factors that may influence the function and structure of the retina and its susceptibility to retinal diseases. The aim of this study was to delineate the influence that biological sex and age exert on the retinal structural and ultrastructural changes in mice and to identify the age-related miRNA dysregulation profiles in the retina by gender. Experiments were undertaken on male and female Balb/c aged 24 months (approximately 75–85 years in humans) compared to the control (3 months). The retinas were analyzed by histology, transmission electron microscopy, and age-related miRNA expression profile analysis. Retinas of both sexes showed a steady decline in retinal thickness as follows: photoreceptor (PS) and outer layers (p < 0.01 for the aged male vs. control; p < 0.05 for the aged female vs. control); the inner retinal layers were significantly affected by the aging process in the males (p < 0.01) but not in the aged females. Electron microscopy revealed more abnormalities which involve the retinal pigment epithelium (RPE) and Bruch’s membrane, outer and inner layers, vascular changes, deposits of amorphous materials, and accumulation of lipids or lipofuscins. Age-related miRNAs, miR-27a-3p (p < 0.01), miR-27b-3p (p < 0.05), and miR-20a-5p (p < 0.05) were significantly up-regulated in aged male mice compared to the controls, whereas miR-20b-5p was significantly down-regulated in aged male (p < 0.05) and female mice (p < 0.05) compared to the respective controls. miR-27a-3p (5.00 fold; p < 0.01) and miR-27b (7.58 fold; p < 0.01) were significantly up-regulated in aged male mice vs. aged female mice, whereas miR-20b-5p (−2.10 fold; p < 0.05) was significantly down-regulated in aged male mice vs. aged female mice. Interestingly, miR-27a-3p, miR-27b-3p, miR-20a-5p, and miR-20b-5p expressions significantly correlated with the thickness of the retinal PS layer (p < 0.01), retinal outer layers (p < 0.01), and Bruch’s membrane (p < 0.01). Our results showed that biological sex can influence the structure and function of the retina upon aging, suggesting that this difference may be underlined by the dysregulation of age-related mi-RNAs.


Author(s):  
Jazmin A Cole ◽  
Mackenzie N Kehmeier ◽  
Bradley R Bedell ◽  
Sahana Krishna Kumaran ◽  
Grant D Henson ◽  
...  

Abstract Vascular endothelial function declines with age on average, but there is high variability in the magnitude of this decline within populations. Measurements of frailty, known as frailty index (FI), can be used as surrogates for biological age, but it is unknown if frailty relates to the age-related decline in vascular function. To examine this relation, we studied young (4-9 months) and old (23-32 months) C57BL6 mice of both sexes. We found that FI was greater in old compared with young mice, but did not differ between old male and female mice. Middle cerebral artery (MCA) and mesenteric artery endothelium-dependent dilation (EDD) also did not differ between old male and female mice; however, there were sex differences in the relations between FI and EDD. For the MCA, FI was inversely related to EDD among old female mice, but not old male mice. In contrast, for the mesenteric artery, FI was inversely related to EDD among old male mice, but not old female mice. A higher FI was related to a greater improvement in EDD with the superoxide scavenger TEMPOL in the MCAs for old female mice and in the mesenteric arteries for old male mice. FI related to mesenteric artery gene expression negatively for extracellular superoxide dismutase (Sod3) and positively for interleukin-1β (Il1b). In summary, we found that the relation between frailty and endothelial function is dependent on sex and the artery examined. Arterial oxidative stress and pro-inflammatory signaling are potential mediators of the relations of frailty and endothelial function.


1992 ◽  
Vol 73 (1) ◽  
pp. 71-74 ◽  
Author(s):  
B. M. Block ◽  
S. R. Barry ◽  
J. A. Faulkner

We hypothesized that methylxanthines, such as aminophylline, increase the power developed by submaximally activated frog skeletal muscles by increasing the force developed at any given velocity of shortening. Frog semitendinosus muscles were excised and tested at 20 degrees C in oxygenated control and aminophylline Ringer solutions. Force-velocity relationships were determined and power was calculated from muscles stimulated at frequencies of 80 and 300 Hz. The 300-Hz frequency of stimulation produced a maximum rate of force development. In 50 and 500 microM aminophylline, twitch force increased by 25 +/- 12 and 75 +/- 13%, respectively. Aminophylline did not affect maximum isometric force generation or the shortening velocity at any relative load. At 80-Hz stimulation and in the presence of 500 microM aminophylline, power increased by an average of 11% at 10 of 14 relative loads. At maximum frequencies of stimulation, aminophylline had no effect on any measured parameter. We conclude that aminophylline increases the power developed by submaximally activated frog muscles through an increase in the force generated particularly at the lower velocities of shortening.


2019 ◽  
Author(s):  
Gabriel Galea ◽  
Peter J Delisser ◽  
Lee Meakin ◽  
Lance E Lanyon ◽  
Joanna S Price ◽  
...  

AbstractThe primary aim of bone anabolic therapies is to strategically increase bone mass in skeletal regions likely to experience high strains. This is naturally achieved by mechanical loading of the young healthy skeleton. However, these bone anabolic responses fail with age. Here, we applied site specificity analysis to map regional differences in bone anabolic responses to axial loading of the tibia (tri-weekly, for two weeks) between young (19-week-old) and aged (19-month-old), male and female mice. Loading increased bone mass specifically in the proximal tibia in both sexes and ages. Young female mice gained more cortical bone than young males in specific regions of the tibia. However, these site-specific sex difference were lost with age such that bone gain following loading was not significantly different between old males and females. Having previously demonstrated that prior and concurrent disuse enhances bone gain following loading in old females, we established whether this “rescue” is sex-specific. Old male mice were subjected to sciatic neurectomy or sham surgery, and tri-weekly loading was initiated four days after surgery. Disuse augmented cortical bone gain in response to loading in old male mice, but only in the regions of the tibia which were load-responsive in the young. Increased understanding of how locally-activated load-responsive processes lead to site-specific bone formation, and how the age-related diminution of these processes can be site-specifically enhanced by disuse, may lead to the next generation of strategic bone anabolic therapies.HighlightsSex differences in cortical tissue area of young and old mice are not site-specificThe loading response in young, but not old, mice is sex- and site-specificThe cortical loading response is site-specifically enhanced by disuse in old mice of both sexesThe trabecular loading response can be rescued by disuse in old male, but not female, mice


2019 ◽  
Vol 69 (5) ◽  
pp. 374-383
Author(s):  
Brian J Smith ◽  
Kate E P Bruner ◽  
Lon V Kendall

Female urine-induced male mice ultrasonic vocalizations (FiUSV) are ultrasonic vocalizations produced by adult male mice after presentation of adult female urine, whereas intruder-induced ultrasonic vocalizations (IiUSV) are produced by resident adult female mice when interacting with an intruder female mouse. These affiliative behaviors may be reduced when mice have decreased wellbeing or are in pain and distress. To determine whether FiUSV and IiUSV can be used as proxy indicators of animal wellbeing, we assessed FiUSV produced by male C57BL/6J mice in response to female urine and IiUSV produced by female C57BL/6J mice in response to a female intruder at baseline and 1 and 3 h after administration of a sublethal dose of LPS (6 or 12.5 mg/kg IP) or an equal volume of saline. Behavior was assessed by evaluating orbital tightness, posture, and piloerection immediately after USV collection. We hypothesized that LPS-injected mice would have a decreased inclination to mate or to interact with same-sex conspecifics and therefore would produce fewer USV. At baseline, 32 of 33 male mice produced FiUSV (149 ± 127 USV in 2 min), whereas all 36 female mice produced IiUSV (370 ± 156 USV in 2 min). Saline-injected mice showed no change from baseline at the 1- and 3-h time points, whereas LPS-injected mice demonstrated significantly fewer USV than baseline, producing no USV at both 1 and 3 h. According to orbital tightness, posture, and piloerection, LPS-injected mice showed signs of poor wellbeing at 3 h but not 1 h. These findings indicate that FiUSV and IiUSV can be used as proxy indicators of animal wellbeing associated with acute inflammation in mice and can be detected before the onset of clinical signs.


2008 ◽  
Vol 104 (4) ◽  
pp. 1109-1115 ◽  
Author(s):  
Nicole C. Lockhart ◽  
Susan V. Brooks

Skeletal muscles can be injured by their own contractions, especially when the muscle is stretched during a lengthening contraction. Exposing a muscle to a conditioning protocol of stretches without activation (passive stretches) before lengthening contractions reduces contraction-induced injury. Although passive stretching does not damage muscle fibers, neutrophils are elevated in the muscle after passive stretches. Our purpose was to investigate the relationship between neutrophil accumulation following passive stretches and the protection from subsequent contraction-induced injury provided by the passive stretches. Our hypothesis was that passive stretch conditioning would not provide protection from subsequent lengthening contraction-induced injury under circumstances when the increase in muscle neutrophils in response to the conditioning was prevented. Extensor digitorum longus muscles of mice were conditioned with passive stretches 14 days before exposure to a protocol of damaging lengthening contractions. Mice were either untreated or treated with an antibody (RB6-8C5) that reduced the level of circulating neutrophils by over 95% before administration of passive stretches. Neutrophil levels recovered in treated mice by the time lengthening contractions were performed. Lengthening contractions were also administered to muscles with no prior exposure to passive stretches. Maximum isometric force, number of damaged fibers, and muscle neutrophil concentration were measured 3 days after lengthening contractions. Compared with nonconditioned control muscles, the severity of contraction-induced injury was not reduced by prior passive stretch conditioning when mice were treated with RB6-8C5 before conditioning. We conclude that neutrophils contribute to adaptations that protect muscles from injury.


2001 ◽  
Vol 8 (2) ◽  
pp. 95-106 ◽  
Author(s):  
Richard Aspinall ◽  
Deborah Andrew

Age associated thymic atrophy has been shown to be linked to problems with rearrangement of the β chain of the T cell receptor (TCR) in male mice during the early phases of the intrathymic T cell developmental pathway. In this study, thymic atrophy in female mice was found to occur at a different rate than in male mice. At 9 months of age there was a significantly greater number of cells in the thymus of female mice compared with male mice, with the major difference found in the CD4+CD8+populations. The thymii of female mice at 9 months of age contained double the number of these cells compared with male mice. Analysis of the CD4+CD8+cells at 9 months of age demonstrated increased numbers of cells expressing higher levels of CD3 in females compared with males indicating that in females more of these cells were producing successful αβTCR pairings. In F5 transgenic mice comparison of the CD4+CD8+population revealed no significant difference in their absolute numbers at 9 months of age. These results indicate that the gender differences at this time point were due to fewer permitted divisions prior to the expression of a selectable TCR α chain within the CD4+CD8+populations in male compared with female mice. This gender difference was not due to the action of testosterone and unlikely to be due to differences in the level of oestrogen. The potential mechanisms of this difference may be related to a regulatory feedback of peripheral T cells on the developing thymocyte populations. Such age related changes in the numbers of cells within distinct thymic subpopulations leads to the possibility that the potential repertoire in females is greater than in males later in life.


1955 ◽  
Vol 12 (4) ◽  
pp. 261-266 ◽  
Author(s):  
JUNE EAST

SUMMARY Dry powdered seeds of the legume Psoralea corylifolia L. proved to be oestrogenic when included in the normal diet of adult female mice at levels calculated to give an intake of 0·35 g or 0·175 g seed/day. Both spayed and intact females exhibited intense vaginal cornification during treatment, but the effect was reversible. The fertility of adult females was impaired by consumption of 0·35 g Psoralea seed for 37–77 days, and an abnormal proportion of matings made with treated or normal partners was infertile, resulting in pseudopregnancies. The animals recovered within 1 week of transfer to a normal diet. The fertility of male mice was not impaired by treatment for 46 days. Consumption of 0·25 g Psoralea seed daily precipitated vaginal opening in immature female mice. The oestrogenic potency of the plant material was low and psoralen(e) (furo-2:3:7:6-coumarin), known to occur in the kernel of Psoralea corylifolia, was not the active constituent.


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