Age-related Changes In Skeletal Muscle Research Articles

Роль вітаміну D та лікувальної фізичної культури в корекції саркопенії

Актуальність. На сьогодні основними напрямками профілактики та терапії саркопенії є корекція харчування, фізичні навантаження, терапія вітаміном D. Мета дослідження: оцінити роль вітаміну D та лікувальної фізкультури в корекції змін скелетної м’язової тканини в жінок у постменопаузальному періоді. Матеріали та методи. Обстежено 38 жінок від 53 до 82 років, які були розподілені на три групи: 1-ша група — контрольна (n = 10), 2-га — жінки (n = 11), які отримували вітамін D, 3-тя — жінки (n = 17), які отримували вітамін D та виконували комплекс фізичних вправ «Отаго» протягом 12 місяців. Візити до центру з метою оцінки їх стану проводилися кожні 3 місяці. Визначення рівня 25(OH)D здійснювали за допомогою імунохемілюмінесцентного методу ECLIA на аналізаторі Elecsys 2010 (Roche Diagnostics, Німеччина). Показники знежиреної маси оцінювали за допомогою двофотонної рентгенівської абсорбціометрії (Prodigy, GEHC Lunar, Madison, WI, США). Для оцінки сили та функції скелетної мускулатури використовували кистьову динамометрію та функціональні тести. При аналізі застосовували пакети програм Statistiсa 6.0 Copyright© StatSoft, Inc. 1984–2001, Serial number 31415926535897. Результати. У жінок контрольної групи встановлено вірогідне збільшення рівня 25(OH)D через 9 місяців (9 місяців — р = 0,03), що пояснюємо сезонними коливаннями. У жінок 2-ї та 3-ї груп рівень 25(OH)Dвірогідно збільшивсячерез 3, 6, 9 та 12 місяців спостереження (р < 0,05). При оцінці апендикулярної знежиреної маси протягом 12 місяців спостереження вірогідних відмінностей не виявлено. Сила м’язів вірогідно збільшувалась у 3-ї групі обстежених жінок через 9 місяців спостереження (р = 0,01), у жінок 1-ї та 2-ї груп — вірогідно не змінювалась. У жінок 3-ї групи було встановлено вірогідне покращання статичного балансування (р = 0,01). Частота падінь у жінок контрольної групи вірогідно зросла через 12 місяців, 2-ї групи — не змінювалась, 3-ї групи — вірогідно зменшилась. Висновки. При використанні комплексної терапії вітаміном D та лікувальною фізкультурою «Отаго» у жінок у постменопаузальному періоді протягом 12 місяців спостерігалось вірогідне покращання щоденної активності, статичного балансування, сили скелетних м’язів та зменшення частоти падінь.

Meta-analysis of genome-wide DNA methylation and integrative omics of age in human skeletal muscle.

BackgroundKnowledge of age‐related DNA methylation changes in skeletal muscle is limited, yet this tissue is severely affected by ageing in humans.MethodsWe conducted a large‐scale epigenome‐wide association study meta‐analysis of age in human skeletal muscle from 10 studies (total n = 908 muscle methylomes from men and women aged 18–89 years old). We explored the genomic context of age‐related DNA methylation changes in chromatin states, CpG islands, and transcription factor binding sites and performed gene set enrichment analysis. We then integrated the DNA methylation data with known transcriptomic and proteomic age‐related changes in skeletal muscle. Finally, we updated our recently developed muscle epigenetic clock (https://bioconductor.org/packages/release/bioc/html/MEAT.html).ResultsWe identified 6710 differentially methylated regions at a stringent false discovery rate <0.005, spanning 6367 unique genes, many of which related to skeletal muscle structure and development. We found a strong increase in DNA methylation at Polycomb target genes and bivalent chromatin domains and a concomitant decrease in DNA methylation at enhancers. Most differentially methylated genes were not altered at the mRNA or protein level, but they were nonetheless strongly enriched for genes showing age‐related differential mRNA and protein expression. After adding a substantial number of samples from five datasets (+371), the updated version of the muscle clock (MEAT 2.0, total n = 1053 samples) performed similarly to the original version of the muscle clock (median of 4.4 vs. 4.6 years in age prediction error), suggesting that the original version of the muscle clock was very accurate.ConclusionsWe provide here the most comprehensive picture of DNA methylation ageing in human skeletal muscle and reveal widespread alterations of genes involved in skeletal muscle structure, development, and differentiation. We have made our results available as an open‐access, user‐friendly, web‐based tool called MetaMeth (https://sarah‐voisin.shinyapps.io/MetaMeth/).

Effects Of Mild Hypoxic Conditions On Mrna Expression Of Spinal Cord In The Young And Old Mouse

We have developed a method to evaluate motoneuron plasticity by real-time RT-PCR analysis for whole spinal cord. PURPOSE: In this study, we examined effects of mild hypoxic conditions on mRNA expression of spinal cord as well as skeletal muscle in young and old mouse. METHODS: Young (12-week old, n=16) and old (20-month old, n=17) mice were divided into three groups of control, continuous hypoxia, and intermittent hypoxia. Both hypoxic groups were subjected to exposure for 5 days under oxygen concentration of 16%. The intermittent hypoxic group was exposed six times to an oxygen concentration of 16% intermittently every hour for 12 hours of the light day of the day. Immediately after completion of the exposure, the spinal cord (Cervical 3 - 6 and Lumber 2 - 5) as well as muscles (diaphragm and gastrocnemius muscles) were removed and mRNA expression levels were investigated using real time RT-PCR system. RESULTS: Although the mRNA expression levels of PGC1α and VEGF-A were significantly (P < 0.05) higher in diaphragm than gastrocnemius muscles, these mRNA expressions levels were not affected by hypoxic stimulation. While, the mRNA expression levels of muscle remodeling factors (Pax7, MyoD, BDNF, and MHCe) were significantly (P < 0.05) higher in hypoxic condition than control group. Compared with young mice, the expression levels of inflammatory cytokine receptor (IL-6Rα) and neurotrophic factors (BDNF, VEGF-A) of muscles increased in old mice. The increased expressions may be considered to be an indispensable adaptive change for age-related changes in skeletal muscle including neuromuscular junction. In the both hypoxia groups, the mRNA expression level of neurotrophic factors (VEGF-A, FGF2) significantly (P < 0.05) increased in the cervical, but not in the lumbar spinal cord. CONCLUSIONS: We concluded that the mRNA expressions of trophic factor were changed by hypoxic stimulation not only in the muscle but also in the cervical spinal cord.

The relationships between sarcopenic skeletal muscle loss during ageing and macronutrient metabolism, obesity and onset of diabetes

Skeletal muscle is integral to the metabolism and utilisation of macronutrients; however, substantial muscle loss and morphological changes occur with ageing. These are associated with loss of muscle function and accelerate rapidly from the age of 60 years, leading to the conditions of sarcopenia and frailty. As the relationship between muscle ageing and macronutrient metabolism and utilisation has seen limited research to date, this review focuses on the interactions between skeletal muscle changes during ageing, metabolism and utilisation of fat, carbohydrates and overall energy expenditure.Skeletal muscle contributes less to resting energy expenditure during ageing, potentially contributing to onset of obesity from middle age. Age-related changes to skeletal muscle lead to glucose dysregulation, with consequent reduction in glycaemic control, increased insulin resistance and ultimately onset of type-2 diabetes. Recent studies indicate that high total fat and SFA intake are detrimental to skeletal muscle, while higher intakes of PUFA are protective. Age-associated changes in skeletal muscle may also reduce total fatty acid utilisation.In conclusion, further research is needed to understand the relationships between macronutrient metabolism and utilisation and age-related changes to skeletal muscle. No dietary recommendations exist specifically for skeletal muscle health during ageing, but we advise individuals to follow healthy eating guidelines, by consuming sufficient protein, fruit and vegetables, and limited SFA and to maintain physically active lifestyles. Clinicians responsible for managing type-2 diabetes need to be aware of growing evidence relating age-related skeletal muscle changes to diabetes onset and progression.

The Biological Foundations of Sarcopenia: Established and Promising Markers.

Sarcopenia, the progressive loss of muscle mass and strength, is one of the major health issues in older adults, given its high prevalence accompanied by huge clinical and socioeconomic implications. Age-related changes in skeletal muscle can be attributed to mechanisms both directly and indirectly related to muscle homeostasis. Indeed, a wide spectrum of age-related modifications in the organism was shown to play a key role in the pathogenesis of sarcopenia. Not surprisingly, sarcopenia has sometimes been indicated as a syndrome stemming from the aging process, and not as univocal standalone disease. Due to the multidimensionality of sarcopenia, a single biomarker approach is not enough to explain the biology of this condition. The aim of this review is to suggest innovative and promising sarcopenia markers investigating the link between skeletal muscle and brain. Indeed, as a neurological origin of sarcopenia has been hypothesized, a new perspective on sarcopenia biomarkers may focus on the dysfunction of the neuromuscular junctions (NMJs). The core SNARE synaptosomal-associated protein of 25 kDa (SNAP25) accumulates in the plasma membrane of nerve terminals at NMJs and regulates exocytosis at peripheral and central synapses. Interestingly, mice studies have shown that SNAP25 affects the neuromuscular function. SNARE complex and, in particular, SNAP25 may represent a promising pathway to explore the molecular and cellular mechanisms regulating muscular homeostasis and concur at profiling the sarcopenia biological background.

Higher Protein Diets Oppose Changes in Skeletal Muscle Transcriptome with Age (OR18-03-19)

ObjectivesAdvancing age during adulthood is associated with deterioration of skeletal muscle (SkM) structure and function (i.e., sarcopenia). Currently, high-protein diets are one of the few recommended therapies to attenuate sarcopenia. However, the mechanisms by which high-protein diets may improve SkM health are not fully understood. The objective of this study was to compare changes in the SkM transcriptome that occur with age (AGE: old vs. young adults) to changes in the SkM transcriptome of older adults in response to protein diets (PROTEIN: high protein vs. low protein diet). MethodsTwo previously published microarray datasets were used for this analysis. The AGE dataset included SkM transcriptomic data from 15 young (25 ± 1 years) and 21 older (78 ± 1 years) adults. The PROTEIN dataset included SkM transcriptomic data obtained from 10 older (72 ± 6 years) adults who consumed either a high (1.0 g protein x kg body wt–1x d–1) or a low (0.5 g protein x kg body wt–1x d–1) protein diet for 18 days. For both studies, morning fasting SkM biopsies were obtained from the vastus lateralis. RNA was extracted, and RNA quality and quantity was checked prior to microarray analysis. A False Discovery Rate correction was used to adjust for multiple comparisons. Differentially expressed genes were uploaded into Ingenuity Pathway Analysis (IPA), and upstream regulators, canonical pathways, and cellular and molecular functions were compared between the AGE and PROTEIN. ResultsThere were 11 common upstream regulators between the AGE and PROTEIN, including TGFB1, CREB1, TP53, ATF4, and FOXO1 that had opposing differences in regulation with the higher protein diet (Table 1). Similarly, there were 4 common canonical pathways between AGE and PROTEIN. Three of the four pathways had opposing changes in regulation including the Sirtuin Signaling, Nucleotide Excision Repair, and Integrin Signaling pathways. Lastly, there were three common Cellular and Molecular Functions (Organismal Death, Apoptosis, Cell Movement), all of which had opposing changes AGE vs. PROTEIN. ConclusionsThese results suggest that high protein diets alter the SkM transcriptome in older adults and may oppose age-related changes in the SkM, particularly those of tissue remodeling, nutrient sensing, and inflammation. Additionally, inadequate protein intake may promote age-related changes in SkM. Funding SourcesNA Supporting Tables, Images and/or Graphs▪

Correlation between grip strength and pulmonary function and respiratory muscle strength in stroke patients over 50 years of age.

Age-related skeletal muscle changes may impact respiratory muscle function, and low muscle mass is associated with low pulmonary function in older adults. Stroke not only causes weakness in the muscles of the upper and lower limbs, but it can also affect the respiratory system. This study aimed to investigate the relationships between grip strength and pulmonary function and respiratory muscle strength in stroke patients over 50 years of age. Fifty-one patients (68.69±10.40 years) who had been clinically diagnosed with ischemic or hemorrhagic stroke were included in this study. We measured these patients’ forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), peak expiratory flow (PEF), maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and hand grip strength. The data were analyzed using descriptive statistics and Pearson correlation analysis. Grip strength showed significant correlations with FVC (r=0.686, P=0.000), FEV1 (r=0.607, P=0.000), PEF (r=0.494, P=0.000), MIP (r=0.239, P=0.091), and MEP (r=0.348, P=0.012). This study demonstrated that grip strength is associated with pulmonary function and MEP in stroke patients over 50 years of age.

Utilizing Next Generation Sequencing to Describe Age-Related Skeletal Muscle Changes with Bed Rest

Short-term bed rest is used to simulate periods of disuse experienced during hospital visitation. In our previous reports, we found that 5d of bed rest induced a ~4% loss of skeletal muscle mass in OLD (60-79 y) but not YOUNG (18-28 y) subjects (Interaction: P < 0.001). Identifying muscle transcriptional events that underlie this consequence of bed rest will help identify therapeutic targets to offset muscle loss in vulnerable older adult populations. PURPOSE: To compare the gene transcriptome response between YOUNG and OLD skeletal muscle after bed rest and identify a transcriptional program that underlies rapid loss of muscle mass. METHODS: RNA was isolated and sequenced (HiSeq, Illumina; DESeq, R) from muscle biopsies obtained from the vastus lateralis of YOUNG (N=9; 22.9 ± 1.1 y, 171.6 ± 2.0 cm, 65.6 ± 4.6 kg) and OLD (N=18; 67.6 ± 1.3 y, 173.7 ± 1.8 cm, 75.7 ± 2.2 kg) men and women before and after five days of bed rest (Tanner et al 2015; Reidy et al 2017). RESULTS: After bed rest, 551 genes responded similarly and 61 genes were differentially regulated between YOUNG and OLD (P < 0.05). Ingenuity Pathway Analysis identified the top commonly regulated pathways to be related to Actin Cytoskeleton Signaling, ILK Signaling, Calcium Signaling, and Mitochondrial Dysfunction. Out of the differentially regulated genes, 51 were altered in YOUNG (42 increased, 9 decreased) but were unresponsive in OLD after bed rest (P < 0.05). On the other hand, 9 genes were altered only in OLD as a result of bed rest (P < 0.05) of which 5 are protein coding (MRPL49, HIST1H2BC: increased; PXDNL, NEXN, MAGI2: decreased). These genes code for proteins related to mitochondrial function, DNA structure, oxidative stress, Z-disc stabilization, and activin signaling, respectively. CONCLUSION: Our preliminary results indicate that altered gene expression in YOUNG in response to bed rest may be indicative of a compensatory expression profile to combat muscle loss. Additional investigation of the differentially regulated gene responses in young and old adults are ongoing in efforts to further describe underlying molecular events that occur in response to bed rest. Supported by NIH Grant R01 AG050781.

Human neuromuscular aging: Sex differences revealed at the myocellular level

Age-related muscle loss (sarcopenia) is a major clinical problem affecting both men and women – accompanied by muscle weakness, dysfunction, disability, and impaired quality of life. Current definitions of sarcopenia do not fully encompass the age-related changes in skeletal muscle. We therefore examined the influence of aging and sex on elements of skeletal muscle health using a thorough histopathological analysis of myocellular aging and assessments of neuromuscular performance. Two-hundred and twenty-one untrained males and females were separated into four age cohorts [mean age 25 y (n = 47), 37 y (n = 79), 61 y (n = 51), and 72 y (n = 44)]. Total (−12%), leg (−17%), and arm (−21%) lean mass were lower in both 61 y and 72 y than in 25 y or 37 y (P < 0.05). Knee extensor strength (−34%) and power (−43%) were lower (P < 0.05) in the older two groups, and explosive sit-to-stand power was lower by 37 y (P < 0.05). At the histological/myocellular level, type IIx atrophy was noted by 37 y and type IIa atrophy by 61 y (P < 0.05). These effects were driven by females, noted by substantial and progressive type IIa and IIx atrophy across age. Aged female muscle displayed greater within-type myofiber size heterogeneity and marked type I myofiber grouping (~5-fold greater) compared to males. These findings suggest the predominant mechanisms leading to whole muscle atrophy differ between aging males and females: myofiber atrophy in females vs. myofiber loss in males. Future studies will be important to better understand the mechanisms underlying sex differences in myocellular aging and optimize exercise prescriptions and adjunctive treatments to mitigate or reverse age-related changes.

Biochemical isolation of myonuclei employed to define changes to the myonuclear proteome that occur with aging.

SummarySkeletal muscle aging is accompanied by loss of muscle mass and strength. Examining changes in myonuclear proteins with age would provide insight into molecular processes which regulate these profound changes in muscle physiology. However, muscle tissue is highly adapted for contraction and thus comprised largely of contractile proteins making the nuclear proteins difficult to identify from whole muscle samples. By developing a method to purify myonuclei from whole skeletal muscle, we were able to collect myonuclei for analysis by flow cytometry, biochemistry, and mass spectrometry. Nuclear purification dramatically increased the number and intensity of nuclear proteins detected by mass spectrometry compared to whole tissue. We exploited this increased proteomic depth to investigate age‐related changes to the myonuclear proteome. Nuclear levels of 54 of 779 identified proteins (7%) changed significantly with age; these proteins were primarily involved in chromatin maintenance and RNA processing. To determine whether the changes we detected were specific to myonuclei or were common to nuclei of excitatory tissues, we compared aging in myonuclei to aging in brain nuclei. Although several of the same processes were affected by aging in both brain and muscle nuclei, the specific proteins involved in these alterations differed between the two tissues. Isolating myonuclei allowed a deeper view into the myonuclear proteome than previously possible facilitating identification of novel age‐related changes in skeletal muscle. Our technique will enable future studies into a heretofore underrepresented compartment of skeletal muscle.

Reducing Undercarboxylated Osteocalcin With Vitamin K Supplementation Does Not Promote Lean Tissue Loss or Fat Gain Over 3 Years in Older Women and Men: A Randomized Controlled Trial.

Osteocalcin (OC) is a vitamin K-dependent protein synthesized during bone formation. Mice injected with the undercarboxylated form of OC (ucOC) had more skeletal muscle mass and less fat mass than sham-treated controls, suggesting a unique metabolic role for ucOC. UcOC decreases in response to vitamin K supplementation. Our objective was to determine the effect of reducing ucOC on change in lean tissue and fat mass in older community-dwelling adults (n = 401, mean ± SD 69 ± 6 years) using data from a randomized controlled trial of vitamin K supplementation. Over 3 years, serum ucOC was reduced by 58% in women and by 61% in men randomized to vitamin K, whereas in the control group, ucOC decreased by 1% in women and 4% in men (supplementation*time p < 0.001 in men and women). However, there were no differences in the change in appendicular lean mass (calculated as arm lean mass + leg lean mass) or total body fat mass between women randomized to vitamin K and control over 3 years (supplementation*time p values all ≥ 0.18) or between men randomized to vitamin K and control (supplementation*time p values all ≥ 0.54). Consistent with these findings, ucOC was not associated cross-sectionally with appendicular lean mass or fat mass in men or women after adjustment for total OC at baseline (all p ≥ 0.12). These findings indicate the undercarboxylated form of OC is not implicated in age-related changes in skeletal muscle or adipose tissue mass in older community-dwelling adults. © 2016 American Society for Bone and Mineral Research.

The role of vitamin D and exercises in correction of age-related skeletal muscle changes in postmenopausal women

The role of vitamin D and exercises in correction of age-related skeletal muscle changes in postmenopausal women

Age-Related Changes in Skeletal Muscle of Cattle.

Sarcopenia, the age-related loss of muscle mass and strength, is a multifactorial condition that represents a major healthcare concern for the elderly population. Although its morphologic features have been extensively studied in humans, animal models, and domestic and wild animals, only a few reports about spontaneous sarcopenia exist in other long-lived animals. In this work, muscle samples from 60 healthy Podolica-breed old cows (aged 15-23 years) were examined and compared with muscle samples from 10 young cows (3-6 years old). Frozen sections were studied through standard histologic and histoenzymatic procedures, as well as by immunohistochemistry, immunofluorescence, and Western blot analysis. The most prominent age-related myopathic features seen in the studied material included angular fiber atrophy (90% of cases), mitochondrial alterations (ragged red fibers, 70%; COX-negative fibers, 60%), presence of vacuolated fibers (75%), lymphocytic (predominantly CD8+) inflammation (40%), and type II selective fiber atrophy (40%). Immunohistochemistry revealed increased expression of major histocompatibility complex I in 36 cases (60%) and sarcoplasmic accumulations of β-amyloid precursor protein-positive material in 18 cases (30%). In aged cows, muscle atrophy was associated with accumulation of myostatin. Western blot analysis indicated increased amount of both proteins-myostatin and β-amyloid precursor protein-in muscles of aged animals compared with controls. These findings confirm the presence of age-related morphologic changes in cows similar to human sarcopenia and underline the possible role of amyloid deposition and subsequent inflammation in muscle senescence.

Vitamin D and muscle function in the elderly: the elixir of youth?

Circumstantial evidence suggests that vitamin D deficiency may contribute to age-related changes in skeletal muscle. This review discusses recent clinical trials examining effects of vitamin D on muscle function in the elderly, and poses the important question: can vitamin D reverse muscle ageing? Observational studies report an association between vitamin D and muscle atrophy/weakness in elderly subjects. Interventional studies suggest that frail, elderly subjects may benefit from vitamin D supplementation by displaying reduced falls, improved muscle function and increased muscle fibre size. However, meta-analyses do not report convincing effects of vitamin D in the elderly. This may be because of multiple factors including lack of standardized endpoints for muscle function, variable study design and different doses of vitamin D supplementation amongst these studies. The evidence base is therefore inconsistent. Vitamin D deficiency may exacerbate ageing of skeletal muscle. However, current evidence that vitamin D supplementation reverses age-related muscle dysfunction is equivocal and does not justify stringent vitamin D targets in the elderly. Until these issues are clarified, the safest option is to aim for conservative vitamin D targets that are sufficient for normal calcium homeostasis.

Effect of green tea on aged rat skeletal muscle

Background Age-related sarcopenia represents a powerful risk factor for the loss of independence and physical disability in the elderly. Green tea contains a series of polyphenols called catechins and has been applied for disease prevention and treatment. Aim of the study To determine the effects of the intake of green tea on age-related changes in skeletal muscle. Materials and methods Thirty female albino rats were divided into three equal groups: group I (control adults) included 6-month-old rats, group II (aged) included 18-month-old rats, and group III (green tea treated) included 12-month-old rats that received green tea at a dose of 300mg/kg body weight in 1.5ml distilled water orally daily by a gastric tube for 6 months. Quadriceps muscle was dissected bilaterally and prepared for light and electron microscopical examination. Morphometric and statistical studies of the mean cross-sectional area of myofibers were carried out in the three studied groups. Results With increasing age, there were focal degeneration and atrophy, and significant decrease in the mean cross-sectional area of myofibers. The connective tissue framework showed increased collagen fiber deposition and deficient reticular fibers. Ultrathin sections showed areas of myofibrillar loss and mitochondria with destroyed cristae. Dense shrunken nuclei of satellite cells were observed. After treatment with green tea, normal-appearing myofibers, except for centrally located nuclei, were observed. The mean cross-sectional area of myofibers increased significantly compared with the aged group. Collagen and reticular fibers were relatively similar to those of the control. Proliferation of satellite cells was observed with restoration of normal myofiber ultrastructure. Conclusion Good regenerative outcome was observed in aged skeletal muscle after the intake of green tea.

Molecular Mechanisms in Aging and Current Strategies to Counteract Sarcopenia

Sarcopenia, the progressive loss of muscle mass with age, is characterized by a deterioration of muscle quantity and quality leading to a gradual slowing of movement and a decline in strength and power. Sarcopenia is a highly significant public health problem. Since these age-related changes in skeletal muscle are largely attributed to various molecular mediators affecting fiber size, mitochondrial homeostatis, and apoptosis, the mechanisms responsible for these deleterious changes present numerous therapeutic targets for drug discovery. We and other researchers demonstrated that a disruption of Akt-mTOR and RhoA-SRF signaling but not Atrogin-1 or MuRF1 contributes to sarcopenia. In addition, sarcopenia seems to include a marked loss of fibers attributable to apoptosis. This review deals with molecular mechanisms of muscle atrophy and provides an update on current strategies (resistance training, myostatin inhibition, treatment with amino acids or testosterone, calorie restriction, etc) for counteracting this loss. Resistance training in combination with amino acid-containing nutrition would be the best candidate to attenuate, prevent, or ultimately reverse age-related muscle wasting and weakness.

Cellular and molecular mechanisms underlying age-related skeletal muscle wasting and weakness

Some of the most serious consequences of ageing are its effects on skeletal muscle. The term 'sarcopenia' describes the slow but progressive loss of muscle mass with advancing age and is characterised by a deterioration of muscle quantity and quality leading to a gradual slowing of movement and a decline in strength. The loss of muscle mass and strength is thought to be attributed to the progressive atrophy and loss of individual muscle fibres associated with the loss of motor units, and a concomitant reduction in muscle 'quality' due to the infiltration of fat and other non-contractile material. These age-related changes in skeletal muscle can be largely attributed to the complex interaction of factors affecting neuromuscular transmission, muscle architecture, fibre composition, excitation-contraction coupling, and metabolism. Given the magnitude of the growing public health problems associated with sarcopenia, there is considerable interest in the development and evaluation of therapeutic strategies to attenuate, prevent, or ultimately reverse age-related muscle wasting and weakness. The aim is to review our current understanding of some of the cellular and molecular mechanisms responsible for age-related changes in skeletal muscle.

Age-Related Changes in Skeletal Muscle as Detected by Diffusion Tensor Magnetic Resonance Imaging

Loss of muscle mass and strength is a common symptom in the elderly population. This is partly a result of the structural changes that occur during the aging process. We applied diffusion tensor magnetic resonance imaging (DTMRI) to determine if water diffusivity in skeletal muscle changes with age. Thirty-eight healthy men, ranging from 27 to 67 years of age, were recruited for this study. The total population was grouped by age (Young < mean age 46.4: n = 20; Old > or = mean age 46.4: n = 18) and body mass index (BMI; Normal < 25: n = 20; Over > or =25: n = 18). The principal, second, and third eigenvalues (lambda(1) > or = lambda(2) > or = lambda(3)), and fractional anisotropy (FA), were calculated from the diffusion tensor of the soleus, lateral and medial gastrocnemius, and anterior tibialis (AT). Analyses included comparison of groups and linear regressions. The older adults showed a significant reduction in the eigenvalues of the plantar flexors ( approximately 7%, p <.05) and FA of AT ( approximately 10%, p <.05) from that of the younger adults. No age differences were observed in the FA of the plantar flexors or eigenvalues of AT. lambda(1) and lambda(2) had a linear dependence on age in the plantar flexors, whereas AT showed age dependence in lambda(3) and FA. We demonstrated that DTMRI is sensitive to age-related changes in muscle, and that the effects of aging differ between the plantar flexors and AT.

Skeletal muscle aging

Average world life expectancy has seen a dramatic rise over the last two centuries although active life expectancy remains relatively unchanged. One reason for this is that aging results in skeletal muscle becoming smaller, weaker and more susceptible to contraction-induced injury. By the age of 70, muscle strength is reduced by around 30–40% and this can have catastrophic effects on quality of life. Despite a vast amount of research into age-related changes in skeletal muscle, the exact mechanisms responsible for this is still unclear and thus treatments to preserve muscle function with aging remain elusive.

Sarcopenia: Age-Related Skeletal Muscle Changes from Determinants to Physical Disability

Human aging is characterized by skeletal muscle wasting, a debilitating condition which sets the susceptibility for diseases that directly affect the quality of life and often limit life span. Sarcopenia, i.e. the reduction of muscle mass and/or function, is the consequence of a reduction of protein synthesis and an increase in muscle protein degradation. In addition, the capacity for muscle regeneration is severely impaired in aging and this can lead to disability, particularly in patients with other concomitant diseases or organ impairment. Immobility and lack of exercise, increased levels of proinflammatory cytokines, increased production of oxygen free radicals or impaired detoxification, low anabolic hormone output, malnutrition and reduced neurological drive have been advocated as being responsible for sarcopenia. It is intriguing to notice that multiple pathways converge on skeletal muscle dysfunction, but the factors involved sometimes diverge to different pathways, thus intersecting at critical points. It is reasonable to argue that the activity of these nodes results from the net balance of regulating mechanisms, as in the case of the GH/IGF-1 axis, the testosterone and cortisol functions, the pro- and anti-inflammatory cytokines and receptors. Both genetic and epigenetic mechanisms operate in regulating the final phenotype, the extent of muscle atrophy and reduction in strength and force generation. It is widely accepted that intervention on lifestyle habits represents an affordable and practical way to modify on a large scale some detrimental outcomes of aging, and particularly sarcopenia. The identification of the molecular chain able to reverse sarcopenia is a major goal of studies on human aging.