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1.
HSS J ; 19(4): 453-458, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37937084

RESUMO

The progression of osteoarthritis of the hip to its end stage and ultimately to total hip arthroplasty (THA) is complex; the multifactorial pathophysiology involves myriad collaborating tissues in and around the diseased joint. We have named the heightened state of periarticular muscle inflammation at the time of surgery "muscle inflammation susceptibility" (MuIS) because it is distinct from systemic inflammation. In this review article, we discuss how MuIS and heightened atrophy-associated signaling in the periarticular skeletal muscles may contribute to reduced muscle mass, impaired muscle quality (ie, through fibrosis), and a muscle microenvironment that challenges regenerative capacity and thus functional recovery from THA. We also review directions for future research that should advance understanding of the key determinants of precision for optimized success of THA for each individual.

2.
Physiol Genomics ; 55(4): 194-212, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36939205

RESUMO

Acute exercise elicits dynamic transcriptional changes that, when repeated, form the fundamental basis of health, resilience, and performance adaptations. While moderate-intensity endurance training combined with conventional resistance training (traditional, TRAD) is often prescribed and recommended by public health guidance, high-intensity training combining maximal-effort intervals with intensive, limited-rest resistance training is a time-efficient alternative that may be used tactically (HITT) to confer similar benefits. Mechanisms of action of these distinct stimuli are incompletely characterized and have not been directly compared. We assessed transcriptome-wide responses in skeletal muscle and circulating extracellular vesicles (EVs) to a single exercise bout in young adults randomized to TRAD (n = 21, 12 M/9 F, 22 ± 3 yr) or HITT (n = 19, 11 M/8 F, 22 ± 2 yr). Next-generation sequencing captured small, long, and circular RNA in muscle and EVs. Analysis identified differentially expressed transcripts (|log2FC|>1, FDR ≤ 0.05) immediately (h0, EVs only), h3, and h24 postexercise within and between exercise protocols. In aaddition, all apparently responsive transcripts (FDR < 0.2) underwent singular value decomposition to summarize data structures into latent variables (LVs) to deconvolve molecular expression circuits and interregulatory relationships. LVs were compared across time and exercise protocol. TRAD, a longer but less intense stimulus, generally elicited a stronger transcriptional response than HITT, but considerable overlap and key differences existed. Findings reveal shared and unique molecular responses to the exercise stimuli and lay groundwork toward establishing relationships between protein-coding genes and lesser-understood transcripts that serve regulatory roles following exercise. Future work should advance the understanding of these circuits and whether they repeat in other populations or following other types of exercise/stress.NEW & NOTEWORTHY We examined small and long transcriptomics in skeletal muscle and serum-derived extracellular vesicles before and after a single exposure to traditional combined exercise (TRAD) and high-intensity tactical training (HITT). Across 40 young adults, we found more consistent protein-coding gene responses to TRAD, whereas HITT elicited differential expression of microRNA enriched in brain regions. Follow-up analysis revealed relationships and temporal dynamics across transcript networks, highlighting potential avenues for research into mechanisms of exercise response and adaptation.


Assuntos
Treinamento de Força , Transcriptoma , Humanos , Adulto Jovem , Transcriptoma/genética , Exercício Físico/fisiologia , Perfilação da Expressão Gênica , Músculo Esquelético/metabolismo
3.
Exp Gerontol ; 173: 112083, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36621699

RESUMO

BACKGROUND: Ageing of skeletal muscle is characterized in some by muscle fiber type grouping due to denervation-reinnervation cycles, but the severity of fiber type grouping varies widely across individuals of the same chronological age. It remains unknown whether fiber type grouping is associated with lower muscle mass and/or reduced physical function in elderly. Therefore, we assessed the relationship between fiber type grouping and indices of muscle mass and physical function in older adults. In addition, we assessed whether fiber type grouping is affected by prolonged resistance training in older adults. METHODS: Twenty young (21 ± 2 y) and twenty older (70 ± 4 y) healthy men participated in the present study. Body composition (DXA-scan), quadriceps cross-sectional area (CT-scan) and muscle strength (1RM) were assessed at baseline (young and old) and following 12 weeks of resistance training (old only). Percutaneous skeletal muscle biopsies from the vastus lateralis were collected at baseline (young and old) and following exercise training (old only). Immunohistochemical analyses were performed to evaluate type I and type II muscle fiber distribution, size, myonuclear content and grouping. RESULTS: At baseline, type II fibers were significantly (P < 0.05) smaller in older compared with young adults (5366 ± 1288 vs 6705 ± 1168 µm2). Whereas no differences were observed in type I, type II fiber grouping was significantly (P < 0.05) lower in older (18 ± 18 %) compared with young (32 ± 25 %) men. No significant correlations were observed between fiber type grouping and muscle mass or physical function. Prolonged resistance training in old men resulted in a significant increase (P < 0.05) in type II fiber size (from 5366 ± 1288 to 6165 ± 1484 µm2) with no significant changes in the proportion of type I muscle fibers found grouped. CONCLUSION: Muscle fiber type grouping is not associated with lower body strength or muscle mass in healthy, older men. In addition, twelve weeks of resistance exercise training results in type II muscle fiber specific hypertrophy but does not affect fiber type grouping.


Assuntos
Treinamento de Força , Masculino , Humanos , Idoso , Feminino , Treinamento de Força/métodos , Fibras Musculares Esqueléticas/fisiologia , Músculo Esquelético/fisiologia , Fibras Musculares de Contração Rápida/patologia , Exercício Físico
4.
Nat Genet ; 54(12): 1816-1826, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36411363

RESUMO

Osteoarthritis is a common progressive joint disease. As no effective medical interventions are available, osteoarthritis often progresses to the end stage, in which only surgical options such as total joint replacement are available. A more thorough understanding of genetic influences of osteoarthritis is essential to develop targeted personalized approaches to treatment, ideally long before the end stage is reached. To date, there have been no large multiancestry genetic studies of osteoarthritis. Here, we leveraged the unique resources of 484,374 participants in the Million Veteran Program and UK Biobank to address this gap. Analyses included participants of European, African, Asian and Hispanic descent. We discovered osteoarthritis-associated genetic variation at 10 loci and replicated findings from previous osteoarthritis studies. We also present evidence that some osteoarthritis-associated regions are robust to population ancestry. Drug repurposing analyses revealed enrichment of targets of several medication classes and provide potential insight into the etiology of beneficial effects of antiepileptics on osteoarthritis pain.


Assuntos
Bancos de Espécimes Biológicos , Loci Gênicos , Humanos , Reino Unido
5.
Physiol Genomics ; 54(12): 501-513, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36278270

RESUMO

The ability of individuals with end-stage osteoarthritis (OA) to functionally recover from total joint arthroplasty is highly inconsistent. The molecular mechanisms driving this heterogeneity have yet to be elucidated. Furthermore, OA disproportionately impacts females, suggesting a need for identifying female-specific therapeutic targets. We profiled the skeletal muscle transcriptome in females with end-stage OA (n = 20) undergoing total knee or hip arthroplasty using RNA-Seq. Single-gene differential expression (DE) analyses tested for DE genes between skeletal muscle overlaying the surgical (SX) joint and muscle from the contralateral (CTRL) leg. Network analyses were performed using Pathway-Level Information ExtractoR (PLIER) to summarize genes into latent variables (LVs), i.e., gene circuits, and link them to biological pathways. LV differences in SX versus CTRL muscle and across sources of muscle tissue (vastus medialis, vastus lateralis, or tensor fascia latae) were determined with ANOVA. Linear models tested for associations between LVs and muscle phenotype on the SX side (inflammation, function, and integrity). DE analysis revealed 360 DE genes (|Log2 fold-difference| ≥ 1, FDR ≤ 0.05) between the SX and CTRL limbs, many associated with inflammation and lipid metabolism. PLIER analyses revealed circuits associated with protein degradation and fibro-adipogenic cell gene expression. Muscle inflammation and function were linked to an LV associated with endothelial cell gene expression highlighting a potential regulatory role of endothelial cells within skeletal muscle. These findings may provide insight into potential therapeutic targets to improve OA rehabilitation before and/or following total joint replacement.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Osteoartrite , Feminino , Humanos , Células Endoteliais , Articulação do Joelho , Osteoartrite/genética , Músculo Esquelético
6.
Int J Mol Sci ; 23(14)2022 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-35886863

RESUMO

Duchenne muscular dystrophy (DMD) is an X-linked recessive disease characterized by skeletal muscle instability, progressive muscle wasting, and fibrosis. A major driver of DMD pathology stems from aberrant upregulation of transforming growth factor ß (TGFß) signaling. In this report, we investigated the major transducers of TGFß signaling, i.e., receptor Smads (R-Smads), in DMD patient skeletal muscle and observed a 48-fold increase in Smad8 mRNA. Smad1, Smad2, Smad3, and Smad5 mRNA were only minimally increased. A similar pattern was observed in the muscle from the mdx5cv mouse. Western blot analysis showed upregulation of phosphorylated Smad1, Smad5, and Smad8 compared to total Smad indicating activation of this pathway. In parallel, we observed a profound diminishment of muscle-enriched microRNAs (myomiRs): miR-1, miR-133a, and miR-133b. The pattern of Smad8 induction and myomiR suppression was recapitulated in C2C12 muscle cells after stimulation with bone morphogenetic protein 4 (BMP4), a signaling factor that we found upregulated in DMD muscle. Silencing Smad8 in C2C12 myoblasts derepressed myomiRs and promoted myoblast differentiation; there was also a concomitant upregulation of myogenic regulatory factors (myogenin and myocyte enhancer factor 2D) and suppression of a pro-inflammatory cytokine (interleukin-6). Our data suggest that Smad8 is a negative regulator of miR-1, miR-133a, and miR-133b in muscle cells and that the BMP4-Smad8 axis is a driver of dystrophic pathology in DMD.


Assuntos
MicroRNAs , Distrofia Muscular de Duchenne , Proteína Smad8 , Animais , Camundongos , Camundongos Endogâmicos mdx , MicroRNAs/genética , MicroRNAs/metabolismo , Músculo Esquelético/metabolismo , Distrofia Muscular de Duchenne/metabolismo , RNA Mensageiro/metabolismo , Proteína Smad8/genética , Proteína Smad8/metabolismo , Fator de Crescimento Transformador beta/metabolismo
7.
BMC Res Notes ; 15(1): 245, 2022 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-35799274

RESUMO

OBJECTIVE: Long INterspersed Element-1 (L1) is an autonomous transposable element in the genome. L1 transcripts that are not reverse transcribed back into the genome can accumulate in the cytoplasm and activate an inflammatory response via the cyclic GMP-AMP (cGAS)-STING pathway. We examined skeletal muscle L1 markers as well as STING protein levels in 10 older individuals (63 ± 11 y, BMI = 30.2 ± 6.8 kg/m2) with end-stage osteoarthritis (OA) undergoing total hip (THA, n = 4) or knee (TKA, n = 6) arthroplasty versus 10 young, healthy comparators (Y, 22 ± 2 y, BMI = 23.2 ± 2.5 kg/m2). For OA, muscle was collected from surgical (SX) and contralateral (CTL) sides whereas single vastus lateralis samples were collected from Y. RESULTS: L1 mRNA was higher in CTL and SX compared to Y (p < 0.001 and p = 0.001, respectively). Protein expression was higher in SX versus Y for ORF1p (p = 0.002) and STING (p = 0.022). While these data are preliminary due to limited n-sizes and the lack of a BMI-matched younger control group, higher L1 mRNA expression, ORF1p and STING protein are evident in older versus younger adults. More research is needed to determine whether cGAS-STING signaling contributes to heightened muscle inflammation during aging and/or OA.


Assuntos
Elementos Nucleotídeos Longos e Dispersos , Músculo Esquelético , Osteoartrite , Idoso , Biomarcadores/metabolismo , Humanos , Articulação do Joelho/metabolismo , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Nucleotidiltransferases/metabolismo , Osteoartrite/genética , RNA Mensageiro/genética , Adulto Jovem
8.
Front Sports Act Living ; 4: 903992, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35721874

RESUMO

As the fields of kinesiology, exercise science, and human movement developed, the majority of the research focused on male physiology and extrapolated findings to females. In the medical sphere, basing practice on data developed in only males resulted in the removal of drugs from the market in the late 1990s due to severe side effects (some life-threatening) in females that were not observed in males. In response to substantial evidence demonstrating exercise-induced health benefits, exercise is often promoted as a key modality in disease prevention, management, and rehabilitation. However, much like the early days of drug development, a historical literature knowledge base of predominantly male studies may leave the exercise field vulnerable to overlooking potentially key biological differences in males and females that may be important to consider in prescribing exercise (e.g., how exercise responses may differ between sexes and whether there are optimal approaches to consider for females that differ from conventional approaches that are based on male physiology). Thus, this review will discuss anatomical, physiological, and skeletal muscle molecular differences that may contribute to sex differences in exercise responses, as well as clinical considerations based on this knowledge in athletic and general populations over the continuum of age. Finally, this review summarizes the current gaps in knowledge, highlights the areas ripe for future research, and considerations for sex-cognizant research in exercise fields.

9.
Front Physiol ; 13: 872745, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35492586

RESUMO

Metformin and statins are currently the focus of large clinical trials testing their ability to counter age-associated declines in health, but recent reports suggest that both may negatively affect skeletal muscle response to exercise. However, it has also been suggested that metformin may act as a possible protectant of statin-related muscle symptoms. The potential impact of combined drug use on the hypertrophic response to resistance exercise in healthy older adults has not been described. We present secondary statin analyses of data from the MASTERS trial where metformin blunted the hypertrophy response in healthy participants (>65 years) following 14 weeks of progressive resistance training (PRT) when compared to identical placebo treatment (n = 94). Approximately one-third of MASTERS participants were taking prescribed statins. Combined metformin and statin resulted in rescue of the metformin-mediated impaired growth response to PRT but did not significantly affect strength. Improved muscle fiber growth may be associated with medication-induced increased abundance of CD11b+/CD206+ M2-like macrophages. Sarcopenia is a significant problem with aging and this study identifies a potential interaction between these commonly used drugs which may help prevent metformin-related blunting of the beneficial effects of PRT. Trial Registration: ClinicalTrials.gov, NCT02308228, Registered on 25 November 2014.

10.
Life Sci Alliance ; 5(9)2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35512829

RESUMO

miR-486 is a muscle-enriched microRNA, or "myomiR," that has reduced expression correlated with Duchenne muscular dystrophy (DMD). To determine the function of miR-486 in normal and dystrophin-deficient muscles and elucidate miR-486 target transcripts in skeletal muscle, we characterized mir-486 knockout mice (mir-486 KO). mir-486 KO mice developed disrupted myofiber architecture, decreased myofiber size, decreased locomotor activity, increased cardiac fibrosis, and metabolic defects were exacerbated in mir-486 KO:mdx 5cv (DKO) mice. To identify direct in vivo miR-486 muscle target transcripts, we integrated RNA sequencing and chimeric miRNA eCLIP sequencing to identify key transcripts and pathways that contribute towards mir-486 KO and dystrophic disease pathologies. These targets included known and novel muscle metabolic and dystrophic structural remodeling factors of muscle and skeletal muscle contractile transcript targets. Together, our studies identify miR-486 as essential for normal muscle function, a driver of pathological remodeling in dystrophin-deficient muscle, a useful biomarker for dystrophic disease progression, and highlight the use of multiple omic platforms to identify in vivo microRNA target transcripts.


Assuntos
Distrofina , MicroRNAs , Animais , Distrofina/genética , Camundongos , Camundongos Endogâmicos mdx , MicroRNAs/genética , MicroRNAs/metabolismo , Músculo Esquelético/metabolismo , Transcriptoma/genética
11.
Compr Physiol ; 12(2): 3193-3279, 2022 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-35578962

RESUMO

For centuries, regular exercise has been acknowledged as a potent stimulus to promote, maintain, and restore healthy functioning of nearly every physiological system of the human body. With advancing understanding of the complexity of human physiology, continually evolving methodological possibilities, and an increasingly dire public health situation, the study of exercise as a preventative or therapeutic treatment has never been more interdisciplinary, or more impactful. During the early stages of the NIH Common Fund Molecular Transducers of Physical Activity Consortium (MoTrPAC) Initiative, the field is well-positioned to build substantially upon the existing understanding of the mechanisms underlying benefits associated with exercise. Thus, we present a comprehensive body of the knowledge detailing the current literature basis surrounding the molecular adaptations to exercise in humans to provide a view of the state of the field at this critical juncture, as well as a resource for scientists bringing external expertise to the field of exercise physiology. In reviewing current literature related to molecular and cellular processes underlying exercise-induced benefits and adaptations, we also draw attention to existing knowledge gaps warranting continued research effort. © 2021 American Physiological Society. Compr Physiol 12:3193-3279, 2022.


Assuntos
Adaptação Fisiológica , Exercício Físico , Exercício Físico/fisiologia , Humanos
12.
Physiol Rep ; 10(10): e15266, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35611788

RESUMO

Spinal cord injury (SCI) leads to major reductions in function, independent living, and quality of life. Disuse and paralysis from SCI leads to rapid muscle atrophy, with chronic muscle loss likely playing a role in the development of the secondary metabolic disorders often seen in those with SCI. Muscle disuse is associated with mitochondrial dysfunction. Previous evidence has suggested targeting the mitochondria with the tetrapeptide SS-31 is beneficial for muscle health in preclinical models that lead to mitochondrial dysfunction, such as cast immobilization or burn injury. We gave young male mice a sham (n = 8) or 65 kdyne thoracic contusion SCI with (n = 9) or without (n = 9) daily administration of 5.0 mg/kg SS-31. Hindlimb muscle mass and muscle bundle respiration were measured at 7 days post-SCI and molecular targets were investigated using immunoblotting, RT-qPCR, and metabolomics. SS-31 did not preserve body mass or hindlimb muscle mass 7 days post-SCI. SS-31 had no effect on soleus or plantaris muscle bundle respiration. SCI was associated with elevated levels of protein carbonylation, led to reduced protein expression of activated DRP1 and reductions in markers of mitochondrial fusion. SS-31 administration did result in reduced total DRP1 expression, as well as greater expression of inhibited DRP1. Gene expression of proinflammatory cytokines and their receptors were largely stable across groups, although SS-31 treatment led to greater mRNA expression of IL1B, TNF, and TNFRSF12A. In summation, SS-31 was not an efficacious treatment acutely after a moderate thoracic contusion SCI in young male mice.


Assuntos
Contusões , Traumatismos da Medula Espinal , Animais , Contusões/complicações , Masculino , Camundongos , Músculo Esquelético/metabolismo , Atrofia Muscular/genética , Atrofia Muscular/prevenção & controle , Qualidade de Vida , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismo
13.
J Appl Physiol (1985) ; 132(6): 1432-1447, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35482328

RESUMO

In older individuals, hypertrophy from progressive resistance training (PRT) is compromised in approximately one-third of participants in exercise trials. The objective of this study was to establish novel relationships between baseline muscle features and/or their PRT-induced change in vastus lateralis muscle biopsies with hypertrophy outcomes. Multiple linear regression analyses adjusted for sex were performed on phenotypic data from older adults (n = 48 participants, 70.8 ± 4.5 yr) completing 14 wk of PRT. Results show that baseline muscle size associates with growth regardless of hypertrophy outcome measure [fiber cross-sectional area (fCSA), ß = -0.76, Adj. P < 0.01; thigh muscle area by computed tomography (CT), ß = -0.75, Adj. P < 0.01; dual-energy X-ray absorptiometry (DXA) thigh lean mass, ß = -0.47, Adj. P < 0.05]. Furthermore, loosely packed collagen organization (CO, ß = -0.44, Adj. P < 0.05) and abundance of CD11b+/CD206- immune cells (ß = -0.36, Adj. P = 0.10) were negatively associated with whole muscle hypertrophy, with a significant sex interaction on the latter. In addition, a composite hypertrophy score generated using all three measures reinforces significant fiber level findings that changes in myonuclei (MN) (ß = 0.67, Adj. P < 0.01), changes in immune cells (ß = 0.48, Adj. P < 0.05; both CD11b+/CD206+and CD11b+/CD206- cells), and capillary density (ß = 0.56, Adj. P < 0.01) are significantly associated with growth. Exploratory single-cell RNA-sequencing of CD11b+ cells in muscle in response to resistance exercise showed that macrophages have a mixed phenotype. Collagen associations with macrophages may be an important aspect in muscle response heterogeneity. Detailed histological phenotyping of muscle combined with multiple measures of growth response to resistance training in older persons identify potential new mechanisms underlying response heterogeneity and possible sex differences.NEW & NOTEWORTHY Extensive analyses of muscle features associated with muscle size and resistance training response in older persons, including sex differences, and evaluation of multiple measures of hypertrophy are discussed. Collagen organization and CD11b-expressing immune cells offer potential new targets to augment growth response in older individuals. A hypertrophy composite score reveals that changes in immune cells, myonuclei, and capillary density are critically important for overall muscle growth while sc-RNAseq reveals evidence for macrophage heterogeneity.


Assuntos
Treinamento de Força , Idoso , Idoso de 80 Anos ou mais , Colágeno , Feminino , Humanos , Hipertrofia , Masculino , Fibras Musculares Esqueléticas/fisiologia , Músculo Esquelético/fisiologia
14.
J Appl Physiol (1985) ; 132(4): 984-994, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35238652

RESUMO

Many individuals with end-stage osteoarthritis (OA) undergo elective total hip/knee arthroplasty (THA/TKA) to relieve pain, improve mobility and quality of life. However, ∼30% suffer long-term mobility impairment following surgery. This may be in part due to muscle inflammation susceptibility (MuIS+), an overt proinflammatory pathology localized to skeletal muscle surrounding the diseased joint, present in some patients with TKA/THA. We interrogated the hypothesis that MuIS+ status results in a perturbed perioperative gene expression profile and decreases skeletal muscle integrity in patients with end-stage OA. Samples were leveraged from the two-site, randomized, controlled trial R01HD084124, NCT02628795. Participants were dichotomized based on surgical (SX) muscle gene expression of TNFRSF1A (TNF-αR). MuIS+/- samples were probed for gene expression and fibrosis. Paired and independent two-tailed t tests were used to determine differences between contralateral (CTRL) and surgical (SX) limbs and between-subject comparisons, respectively. Significance was declared at P < 0.05. Seventy participants (26M/44F; mean age 62.41 ± 8.86 yr; mean body mass index 31.10 ± 4.91 kg/m2) undergoing THA/TKA were clustered as MuIS+ (n = 24) or MuIS- (n = 46). Lower skeletal muscle integrity (greater fibrosis) exists on the SX versus CTRL limb (P < 0.001). Furthermore, MuIS+ versus MuIS- muscle exhibited higher proinflammatory (IL-6R and TNF-α) and catabolic (TRIM63) gene expression (P < 0.001, P = 0.004, and 0.024 respectively), with a trend for greater fibrosis (P = 0.087). Patients with MuIS+ exhibit more inflammation and catabolic gene expression in skeletal muscle of the SX limb, accompanied by decreased skeletal muscle integrity (Trend). This highlights the impact of MuIS+ status emphasizing the potential value of perioperative MuIS assessment to inform optimal postsurgical care.NEW & NOTEWORTHY This study assessed the skeletal muscle molecular characteristics associated with end-stage osteoarthritis and refined an important phenotype, in some patients, termed muscle inflammation susceptibility (MuIS+) that may be an important consideration following surgery. Furthermore, we provide evidence of differential inflammatory and catabolic gene expression between the contralateral and surgical limbs along with differences between the skeletal muscle surrounding the diseased hip versus knee joints.


Assuntos
Miosite , Osteoartrite do Joelho , Osteoartrite , Idoso , Feminino , Fibrose , Humanos , Inflamação/genética , Masculino , Pessoa de Meia-Idade , Músculos , Osteoartrite/genética , Osteoartrite/cirurgia , Osteoartrite do Joelho/genética , Osteoartrite do Joelho/cirurgia , Qualidade de Vida
15.
Geroscience ; 44(3): 1175-1197, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35084687

RESUMO

The aim of the present study was to compare the neuromuscular, morphological, and functional responses to a high-velocity resistance training (HVRT) program between three cohorts: middle-aged adults (40-55 years, n = 18), healthy older adults (> 60 years, n = 18), and mobility-limited older adults (n = 8). Participants were tested before and after a 4-week control period and then assigned to a 12-week HVRT intervention. Investigated outcomes included ultrasound-derived muscle thickness and quality, maximal dynamic strength (1RM), maximal voluntary isometric contraction (MVIC), and muscle activation (sEMG), as well as muscle power and functional performance. After the intervention, quadriceps muscle thickness, 1RM, and sEMG improved in all three groups (all p < 0.05), whereas muscle quality improved only in middle-aged and older participants (p ≤ 0.001), and MVIC only in middle-aged and mobility-limited older adults (p < 0.05). With a few exceptions, peak power improved in all groups from 30-90% 1RM (p < 0.05) both when tested relative to pre-training or post-training 1RM workloads (all p < 0.05). Both mobility-limited older adults and older adults improved their short physical performance battery score (p < 0.05). Chair stand, stair climb, maximal gait speed, and timed up-and-go performance, on the other hand, improved in all three groups (p < 0.05), but no change was observed for habitual gait speed and 6-min walk test performance. Overall, our results demonstrate that a HVRT intervention can build a stronger foundation in middle-aged individuals so that they can better deal with age-related impairments at the same time that it can mitigate already present physiological and functional impairments in older adults with and without mobility-limitation.


Assuntos
Treinamento de Força , Idoso , Humanos , Pessoa de Meia-Idade , Limitação da Mobilidade , Força Muscular/fisiologia , Músculos , Treinamento de Força/métodos , Velocidade de Caminhada
16.
Am J Physiol Endocrinol Metab ; 322(3): E260-E277, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35068187

RESUMO

Age-related declines in cardiorespiratory fitness and physical function are mitigated by regular endurance exercise in older adults. This may be due, in part, to changes in the transcriptional program of skeletal muscle following repeated bouts of exercise. However, the impact of chronic exercise training on the transcriptional response to an acute bout of endurance exercise has not been clearly determined. Here, we characterized baseline differences in muscle transcriptome and exercise-induced response in older adults who were active/endurance trained or sedentary. RNA-sequencing was performed on vastus lateralis biopsy specimens obtained before, immediately after, and 3 h following a bout of endurance exercise (40 min of cycling at 60%-70% of heart rate reserve). Using a recently developed bioinformatics approach, we found that transcript signatures related to type I myofibers, mitochondria, and endothelial cells were higher in active/endurance-trained adults and were associated with key phenotypic features including V̇o2peak, ATPmax, and muscle fiber proportion. Immune cell signatures were elevated in the sedentary group and linked to visceral and intermuscular adipose tissue mass. Following acute exercise, we observed distinct temporal transcriptional signatures that were largely similar among groups. Enrichment analysis revealed catabolic processes were uniquely enriched in the sedentary group at the 3-h postexercise timepoint. In summary, this study revealed key transcriptional signatures that distinguished active and sedentary adults, which were associated with difference in oxidative capacity and depot-specific adiposity. The acute response signatures were consistent with beneficial effects of endurance exercise to improve muscle health in older adults irrespective of exercise history and adiposity.NEW & NOTEWORTHY Muscle transcript signatures associated with oxidative capacity and immune cells underlie important phenotypic and clinical characteristics of older adults who are endurance trained or sedentary. Despite divergent phenotypes, the temporal transcriptional signatures in response to an acute bout of endurance exercise were largely similar among groups. These data provide new insight into the transcriptional programs of aging muscle and the beneficial effects of endurance exercise to promote healthy aging in older adults.


Assuntos
Resistência Física , Transcriptoma , Idoso , Células Endoteliais , Exercício Físico/fisiologia , Humanos , Músculo Esquelético/metabolismo , Resistência Física/fisiologia
17.
FASEB J ; 36(2): e22155, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35044708

RESUMO

The extracellular matrix (ECM) in skeletal muscle plays an integral role in tissue development, structural support, and force transmission. For successful adaptation to mechanical loading, remodeling processes must occur. In a large cohort of older adults, transcriptomics revealed that genes involved in ECM remodeling, including matrix metalloproteinase 14 (MMP14), were the most upregulated following 14 weeks of progressive resistance exercise training (PRT). Using single-cell RNA-seq, we identified macrophages as a source of Mmp14 in muscle following a hypertrophic exercise stimulus in mice. In vitro contractile activity in myotubes revealed that the gene encoding cytokine leukemia inhibitory factor (LIF) is robustly upregulated and can stimulate Mmp14 expression in macrophages. Functional experiments confirmed that modulation of this muscle cell-macrophage axis facilitated Type I collagen turnover. Finally, changes in LIF expression were significantly correlated with MMP14 expression in humans following 14 weeks of PRT. Our experiments reveal a mechanism whereby muscle fibers influence macrophage behavior to promote ECM remodeling in response to mechanical loading.


Assuntos
Matriz Extracelular/metabolismo , Leucócitos Mononucleares/metabolismo , Metaloproteinase 14 da Matriz/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Adulto , Idoso , Animais , Células Cultivadas , Colágeno Tipo I/metabolismo , Feminino , Humanos , Fator Inibidor de Leucemia/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos , Contração Muscular/fisiologia , Músculo Esquelético/metabolismo , Treinamento de Força/métodos
18.
Brain Plast ; 8(2): 153-168, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36721393

RESUMO

An inaugural workshop supported by "The Leo and Anne Albert Charitable Trust," was held October 4-7, 2019 in Scottsdale, Arizona, to focus on the effects of exercise on the brain and to discuss how physical activity may prevent or delay the onset of aging-related neurodegenerative conditions. The Scientific Program Committee (led by Dr. Jeff Burns) assembled translational, clinical, and basic scientists who research various aspects of the effects of exercise on the body and brain, with the overall goal of gaining a better understanding as to how to delay or prevent neurodegenerative diseases. In particular, research topics included the links between cardiorespiratory fitness, the cerebrovasculature, energy metabolism, peripheral organs, and cognitive function, which are all highly relevant to understanding the effects of acute and chronic exercise on the brain. The Albert Trust workshop participants addressed these and related topics, as well as how other lifestyle interventions, such as diet, affect age-related cognitive decline associated with Alzheimer's and other neurodegenerative diseases. This report provides a synopsis of the presentations and discussions by the participants, and a delineation of the next steps towards advancing our understanding of the effects of exercise on the aging brain.

19.
Gait Posture ; 91: 235-239, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34749075

RESUMO

BACKGROUND: Persons with Parkinson's disease (PD) participate in low levels of physical activity. This has prompted interest in developing interventions targeting physical activity behavior in PD. However, the current cut-points to quantify moderate-to-vigorous physical activity (MVPA) developed for PD have been derived from a single, vertical axis using hip-worn accelerometers, and this cut-point may not be applicable for wrist-worn devices. Wrist-worn devices might improve accessibility and compliance with physical activity monitoring in PD. RESEARCH QUESTION: What is the relationship between wrist-based activity counts and energy expenditure during treadmill walking in persons with PD? Do cut-points for quantifying time spent in MVPA differ between persons with PD and controls matched by age and sex? METHODS: The sample included 26 persons with mild-to-moderate PD (Hoehn and Yahr stages 2-3) and 27 age- and sex-matched controls. Participants completed three, 6-minute bouts of walking on a treadmill at three increasing speeds. Vector magnitude was measured using ActiGraph GT3X+ accelerometer worn on the more affected side for persons with PD and the non-dominant side for controls. The rate of oxygen consumption, or energy expenditure, was measured using a portable, open-circuit spirometry system. RESULTS: Our results indicated a strong association between activity counts and energy expenditure for persons with PD and controls with R2 values of 0.94(0.07) and 0.95(0.06), respectively. Persons with PD had a cut-point of 2883(871) counts·min-1; this was significantly lower than the cut-point of 4389(1844) counts·min-1 for controls. CONCLUSION: We generated a PD-specific cut-point for wrist-worn ActiGraph accelerometers among persons with PD, and this was lower than controls. This disease-specific cut-point may provide more accurate measurements of time spent in MVPA in PD.


Assuntos
Doença de Parkinson , Punho , Acelerometria , Exercício Físico , Humanos , Caminhada
20.
Exp Gerontol ; 156: 111593, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34656749

RESUMO

The aging process results in several physiological impairments that, in turn, may predispose older individuals to a series of restrictions on their functional capacity. These impairments are important to understand so that suitable conditions for healthier aging can be pursued. In this review, we first summarize the effects of aging on the neuromuscular system, as well as on the relation between the main age-associated physiological impairments and functional performance with an emphasis on muscle power output. We then proceed to discuss the effects of resistance training, specifically high-velocity resistance training (HVRT), on the aforementioned neuromuscular impairments, and on functional performance in healthy and mobility-limited older adults. Collectively, available evidence suggests that HVRT seems to be a safe and effective intervention for improving muscle power, functional performance, and mobility of older individuals. It also seems that mobility-limited older adults may improve power and functional performance to a greater extent than their healthy counterparts after HVRT, which is in line with the principle of diminishing returns. Considering that only a very limited number of investigations directly compared the effects of HVRT in more than one of the aforementioned groups, studies comparing the adaptations to HVRT of middle-aged adults and older adults with distinct functional capacities would be valuable to determine whether there are differences in neuromuscular adaptations, functional performance, and functional reserve among these groups.


Assuntos
Treinamento de Força , Idoso , Envelhecimento/fisiologia , Humanos , Pessoa de Meia-Idade , Força Muscular/fisiologia , Músculo Esquelético/fisiologia , Músculos , Desempenho Físico Funcional , Treinamento de Força/métodos
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