Measuring Exercise Capacity and Physical Function in Adult and Older Mice.
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ABSTRACT:
SUBMITTER: Graber TG
PROVIDER: S-EPMC8087272 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Micro-dystrophin (μDys) gene therapeutics can improve striated muscle structure and function in different animal models of Duchenne muscular dystrophy. Most studies, however, used young mdx mice that lack a pronounced dystrophic phenotype, short treatment periods, and limited muscle function tests. We, therefore, determined the relative efficacy of two previously described μDys gene therapeutics (rAAV6:μDysH3 and rAAV6:μDys5) in 6-month-old mdx mice using a 6-month treatment regimen and forced exercise. Forelimb and hindlimb grip strength, metabolic rate (VO2 max), running efficiency (energy expenditure), and serum creatine kinase levels similarly improved in mdx mice treated with either vector. Both vectors produced nearly identical dose-responses in all assays. They also partially prevented the degenerative effects of repeated high-intensity exercise on muscle histology, although none of the metrics examined was restored to normal wild-type levels. Moreover, neither vector had any consistent effect on respiration while exercising. These data together suggest that, although μDys gene therapy can improve isolated and systemic muscle function, it may be only partially effective when dystrophinopathies are advanced or when muscle structure is significantly challenged, as with high-intensity exercise. This further suggests that restoring muscle function to near-normal levels will likely require ancillary or combinatorial treatments capable of enhancing muscle strength.
| S-EPMC6939027 | biostudies-literature
Project description:Sarcopenia, the age-related loss of muscle mass and strength, contributes to frailty, functional decline, and reduced quality of life in older adults. Exercise is a recognized therapy for sarcopenia and muscle dysfunction, though not a cure. Muscle power declines at an increased rate compared to force, and force output declines earlier than mass. Thus, there is a need for research of exercise focusing on improving power output and functionality in older adults. Our primary purpose was proof-of-concept that a novel individualized power exercise modality would induce positive adaptations in adult mice, before the exercise program was applied to an aged cohort. We hypothesized that after following our protocol, both adult and older mice would show improved function, though there would be evidence of anabolic resistance in the older mice. Male C57BL/6 mice (12 months of age at study conclusion) were randomized into control (n?=?9) and exercise (n?=?6) groups. The trained group used progressive resistance (with a weighted harness) and intensity (~?4-10 rpm) on a custom motorized running wheel. The mice trained similarly to a human workout regimen (4-5 sets/session, 3 sessions/week, for 12 weeks). We determined significant (p?<?0.05) positive adaptations post-intervention, including: neuromuscular function (rotarod), strength/endurance (inverted cling grip test), training physiology (force/power output per session), muscle size (soleus mass), and power/velocity of contraction (in vitro physiology). Secondly, we trained a cohort of older male mice (28 months old at conclusion): control (n?=?12) and exercised (n?=?8). While the older exercised mice did preserve function and gain benefits, they also demonstrated evidence of anabolic resistance.
| S-EPMC6544743 | biostudies-literature
Project description:Exercise has been shown to improve physical function, mitigate aspects of chronic disease and to potentially alter the trajectory of age-related onset of frailty and sarcopenia. Reliable and valid preclinical models are necessary to elucidate the underlying mechanisms at the intersection of age, exercise, and functional decline. The purpose of this study was to compare, head to head, the effects of two common pre-clinical models of endurance exercise: high intensity interval training (HIIT) and voluntary wheel running (VWR). The hypothesis was that a prescribed and regimented exercise program, HIIT, would prove to be a superior training method to unregulated voluntary exercise, VWR. To investigate this hypothesis, we evaluated adult (n = 24, designated 10 m, aged 6 months at the beginning of the study, 10 months at its completion) and older adult (n = 18, designated 26 m, aging from 22 months to 26 months over the course of the study) C57BL/6 male mice. These mice were randomly assigned (with selection criteria) to a 13-week program of voluntary wheel running (VWR), high intensity interval training (HIIT), or sedentary control (SED). The functional aptitude of each mouse was determined pre- and post-training using our composite CFAB (comprehensive functional assessment battery) scoring system consisting of voluntary wheel running (volitional exercise and activity rate), treadmill (endurance), rotarod (overall motor function), grip meter (forelimb strength), and inverted cling (whole body strength/endurance). To measure sarcopenia, we tracked body mass, body composition (with EchoMRI), plantar flexor torque (in 10 m), and measured muscle wet mass post-training. Overall, adult CFAB scores decreased while body mass and percent body fat increased as they matured; however, exercise significantly mitigated the changes (p < 0.05) compared to SED. Older adults demonstrated preservation of function (CFAB) and reduced body fat (p < 0.05) compared to SED. To conclude, both types of exercise maintained physical function equally in older mice.
| S-EPMC10958787 | biostudies-literature
Project description:OBJECTIVES:Skeletal muscle weakness and an increase in fatigability independently contribute to age-related functional decline. The objective of this study was to examine the combined contribution of these deficiencies (i.e., torque capacity) to physical function, and then to assess the functional implications of progressive resistance training (PRT) mediated-torque capacity improvements in mobility-limited older adults. DESIGN:Randomized controlled trial. SETTING:Exercise laboratory on the Health Sciences campus of an urban university. PARTICIPANTS:Seventy mobility-limited (Short Physical Performance Battery (SPPB) ?9) older adults (~79 yrs). INTERVENTION:Progressive resistance training or home-based flexibility 3 days/week for 12 weeks. MEASUREMENTS:Torque capacity was defined as the sum of peak torques from an isokinetic knee extension fatigue test. Relationships between torque capacity and performance-based and patient-reported functional measures before and after PRT were examined using partial correlations adjusted for age, sex, and body mass index. RESULTS:Torque capacity explained (P<0.05) 10 and 28% of the variance in six-minute walk distance and stair climb time, respectively. PRT-mediated torque capacity improvements were paralleled by increases (P<0.05) in self-reported activity participation (+20%) and advanced lower extremity function (+7%), and associated (P<0.05) with a reduction in activity limitations (r=0.44) and an improved SPPB score (r=0.32). CONCLUSION:Skeletal muscle torque capacity, a composite of strength and fatigue, may be a proximal determinant of physical function in mobility-limited older individuals. To more closely replicate the musculoskeletal demands of real-life tasks, future studies are encouraged to consider the combined interaction of distinct skeletal muscle faculties to overall functional ability in older adults.
| S-EPMC7386562 | biostudies-literature
Project description:ObjectivesThe topic of older adult loneliness commands increasing media and policy attention around the world. Are surveys of aging equipped to measure it? We assess the measurement of loneliness in large-scale aging studies in 31 countries by describing the available measures, testing correlations between them, and documenting their construct validity.MethodsWe use data from several "sister studies" of aging adults around the world. In each country, we document available loneliness measures, test for measurement reliability by examining correlations between different measures of loneliness, and assess how these correlations differ by gender and age group. We then evaluate construct validity by estimating correlations between loneliness measures and theoretically hypothesized constructs related to loneliness: living alone and not having a spouse.ResultsThere is substantial heterogeneity in available measures of loneliness across countries. Within countries with multiple measures, the correlations between measures are high (range 0.384-0.777, median 0.636). Although we find several statistically significant differences in these correlations by gender and age, the differences are small (gender: range -0.098 to 0.081, median -0.026; age group: range -0.194 to 0.092, median -0.003). Correlations between loneliness measures and living alone and being without a spouse are all positive, almost universally statistically significant, and similar in magnitude across countries, supporting construct validity.DiscussionThis article establishes that even single-item measures of loneliness contribute meaningful information in diverse settings. Similar to the measurement of self-rated health, there are nuances to the measurement of older adult loneliness in different contexts, but it has reliable and consistent measurement properties within many countries.
| S-EPMC8363044 | biostudies-literature
Project description:BackgroundObesity exacerbates the age-related decline in physical function and causes frailty in older adults; however, the appropriate treatment for obese older adults is controversial.MethodsIn this 1-year, randomized, controlled trial, we evaluated the independent and combined effects of weight loss and exercise in 107 adults who were 65 years of age or older and obese. Participants were randomly assigned to a control group, a weight-management (diet) group, an exercise group, or a weight-management-plus-exercise (diet-exercise) group. The primary outcome was the change in score on the modified Physical Performance Test. Secondary outcomes included other measures of frailty, body composition, bone mineral density, specific physical functions, and quality of life.ResultsA total of 93 participants (87%) completed the study. In the intention-to-treat analysis, the score on the Physical Performance Test, in which higher scores indicate better physical status, increased more in the diet-exercise group than in the diet group or the exercise group (increases from baseline of 21% vs. 12% and 15%, respectively); the scores in all three of those groups increased more than the scores in the control group (in which the score increased by 1%) (P<0.001 for the between-group differences). Moreover, the peak oxygen consumption improved more in the diet-exercise group than in the diet group or the exercise group (increases of 17% vs. 10% and 8%, respectively; P<0.001); the score on the Functional Status Questionnaire, in which higher scores indicate better physical function, increased more in the diet-exercise group than in the diet group (increase of 10% vs. 4%, P<0.001). Body weight decreased by 10% in the diet group and by 9% in the diet-exercise group, but did not decrease in the exercise group or the control group (P<0.001). Lean body mass and bone mineral density at the hip decreased less in the diet-exercise group than in the diet group (reductions of 3% and 1%, respectively, in the diet-exercise group vs. reductions of 5% and 3%, respectively, in the diet group; P<0.05 for both comparisons). Strength, balance, and gait improved consistently in the diet-exercise group (P<0.05 for all comparisons). Adverse events included a small number of exercise-associated musculoskeletal injuries.ConclusionsThese findings suggest that a combination of weight loss and exercise provides greater improvement in physical function than either intervention alone. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00146107.).
| S-EPMC3114602 | biostudies-literature
Project description:BackgroundHyperkyphosis is common in older adults and associated with low physical function and reduced health related quality of life (HrQol). Improved kyphosis has been previously established in kyphosis-targeted interventions in randomized controlled trials in older adults with hyperkyphosis; however, evidence for improved physical function is conflicting. Few studies have investigated change in physical function after a targeted kyphosis intervention in older adults with low physical function. The primary aim in this descriptive study was to explore change in physical function after a progressive high-intensity 3-month targeted kyphosis exercise and posture training intervention in older adults with low physical function and hyperkyphosis. Secondary aims were to explore change in HrQol, spinal strength and spinal curvature, and adherence and safety of the intervention.MethodsIn this secondary analysis of the Specialized Center of Research (SCOR) Kyphosis randomized trial, 101 community dwelling older men and women with hyperkyphosis who completed the intervention were divided into a low function group (LFG) and high function group (HFG). Baseline characteristics were compared between LFG and HFG. Physical function, HrQol, spinal strength and spinal curvature (kyphosis and lordosis) pre/post intervention change scores were explored within and between groups. Adherence and adverse events were examined in the LFG and HFG.ResultsTwenty-six (26%) older adults were LFG, mean Short Phyiscal Performance Battery (SPPB) 9.62 (SD = 1.17) points. At baseline, the LFG was older than HFG (p = 0.005), experienced more pain, (p = 0.060), had worse physical function and HrQol (p ≤ 0.001), and comparable kyphosis (p = 0.640). SPPB changed 0.62 (95% CI: - 0.20 to 1.44) points in the LFG and - 0.04 (95%CI: - 0.28 to 0.19) points in the HFG, p = 0.020. Gait speed changed 0.04 (95% CI: - 0.02 to 0.10) m/s in the LFG. Kyphosis improved equally in both groups. Adherence to the intervention was 83% in the LFG and 79% in the HFG. There were no adverse events in either group.ConclusionsOlder adults with low physical function and hyperkyphosis may improve physical function after a kyphosis targeted intervention. Older adults with low physical function may safely participate in targeted high-intensity kyphosis exercise and posture training. This observation needs to be confirmed in larger adequately powered studies.Trial registrationClinicaltrials.gov identifier: NCT01766674 .
| S-EPMC7901174 | biostudies-literature
Project description:Cancer treatment increases cardiovascular disease risk, but physical activity (PA) may prevent cardiovascular disease. This study examined whether greater PA was associated with better submaximal exercise capacity and cardiac function during cancer therapy. Participants included 223 women with stage I to III breast cancer (BC) before and 3 months after undergoing treatment and 126 control participants. Leisure-time PA (LTPA) was reported using the Godin-Shephard LTPA questionnaire. Cardiac function was assessed by cardiac magnetic resonance. Submaximal exercise capacity was determined by 6-minute walk distance. BC participants reported similar baseline LTPA scores (24.7; 95% CI: 21.7-28.0) as control participants (29.4; 95% CI: 25.0-34.2). The BC group declined to 16.9 (95% CI: 14.4-19.6) at 3 months relative to 30.8 (95% CI: 26.2-35.8) in control participants. Among BC participants, more LTPA was related to better exercise capacity (β ± SE: 7.1 ± 1.6; 95% CI: 4.0-10.1) and left ventricular (LV) circumferential strain (-0.16 ± 0.07; 95% CI: -0.29 to -0.02). Increased LTPA over the 3 months was associated with decreased likelihood of treatment-induced cardiac dysfunction according to LV circumferential strain classifications (OR: 0.98; 95% CI: 0.97-0.998). BC participants reporting insufficient LTPA according to PA guidelines exhibited deteriorations in exercise capacity (adjusted mean difference ± SE: -29 ± 10 m; P = 0.029), LV end-systolic volume (5.8 ± 1.3 mL; P < 0.001), LV ejection fraction (-3.2% ± 0.8%; P = 0.002), and LV circumferential strain (2.5% ± 0.5%; P < 0.001), but BC participants meeting LTPA guidelines did not exhibit these adverse changes. PA declined during BC therapy; however, PA participation was associated with attenuated declines in exercise capacity and cardiac function that are often observed in this population. (Understanding and Predicting Breast Cancer Events After Treatment [WF97415 UPBEAT]; NCT02791581).
| S-EPMC10635881 | biostudies-literature
Project description:The relationship between the age-associated decline in mitochondrial function and its effect on skeletal muscle physiology and function remain unclear. In the current study, we examined to what extent physical activity contributes to the decline in mitochondrial function and muscle health during aging and compared mitochondrial function in young and older adults, with similar habitual physical activity levels. We also studied exercise-trained older adults and physically impaired older adults. Aging was associated with a decline in mitochondrial capacity, exercise capacity and efficiency, gait stability, muscle function, and insulin sensitivity, even when maintaining an adequate daily physical activity level. Our data also suggest that a further increase in physical activity level, achieved through regular exercise training, can largely negate the effects of aging. Finally, mitochondrial capacity correlated with exercise efficiency and insulin sensitivity. Together, our data support a link between mitochondrial function and age-associated deterioration of skeletal muscle.
| S-EPMC8346468 | biostudies-literature
Project description:Since aging has been associated with increased production of inflammatory biomarkers, the ability to monitor older adults repeatedly is highly desirable, and saliva is an interesting biofluid for the search of biomarkers, as it is easily accessible in a noninvasive manner. However, given the incipient knowledge of salivary biomarkers in aging and its relationship to physical exercise, the present study is aimed at evaluating the protein expression and the levels of inflammatory and NETosis biomarkers in the saliva of practitioners (PE) and nonpractitioners (NPE) of physical exercise older adults. Six (6) practitioner and 4 nonpractitioner older adults were enrolled in this study. Unstimulated whole saliva was collected for analysis of the proteome by label-free mass spectrometry, as well as of the inflammatory status by evaluation of C-reactive protein (CRP), vascular endothelial growth factor (VEGF), and cytokines (TNF-α, interleukin- (IL-) 1β, and IL-8), while NETosis was assessed by myeloperoxidase (MPO) and neutrophil elastase. Regarding oral health, the decayed, missing, and filled teeth (DMF-T) index, bleeding on probing, suppuration, and probing depth measurement (mm) were evaluated. In addition, functional capacity was investigated using the General Physical Fitness Index (GPFI). In relation to the proteome analysis, 93 and 143 proteins were found exclusively in the PE and NPE groups, respectively; 224 proteins were common to both groups. Among these proteins, 10 proteins showed statistical difference (p < 0.05) between the groups: alpha-2-macroglobulin, component 3 of the complement, serotransferrin, and protein soluble in brain acid 1 were less expressed, while lactotransferrin, alpha-amylase 1, S100-A8, S100-A9, lactoperoxidase, and galectin-3 binding protein were more expressed in the PE group. No differences between groups were observed in the analysis of inflammatory and NETosis biomarkers. This study shows the potential utility of saliva for detecting protein biomarkers in a noninvasive biological sample of the elderly population.
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