The role of physical activity in the link between menopausal status and mental well-being

OBJECTIVE To examine the relationship between menopausal status and mental well-being, and whether this relationship varies as a function of physical activity (PA). METHODS Based on a hormonal analysis and bleeding diary, women aged 47 to 55 were categorized as pre (n = 304), early peri (n = 198), late peri (n = 209), or postmenopausal (n = 387). Mental well-being was assessed using the Centre for Epidemiologic Studies Depression Scale, the International Positive and Negative Affect Schedule Short Form, and the Satisfaction with Life Scale. PA was self-reported and categorized as low, medium, and high. Associations between variables were analyzed using multivariate linear regression adjuste…

Estrogen Regulates the Satellite Cell Compartment in Females

SUMMARY Skeletal muscle mass, strength, and regenerative capacity decline with age, with many measures showing a greater deterioration in females around the time estrogen levels decrease at menopause. Here, we show that estrogen deficiency severely compromises the maintenance of muscle stem cells (i.e., satellite cells) as well as impairs self-renewal and differentiation into muscle fibers. Mechanistically, by hormone replacement, use of a selective estrogen-receptor modulator (bazedoxifene), and conditional estrogen receptor knockout, we implicate 17β-estradiol and satellite cell expression of estrogen receptor α and show that estrogen signaling through this receptor is necessary to preven…

Hormone replacement therapy enhances IGF-1 signaling in skeletal muscle by diminishing miR-182 and miR-223 expressions : a study on postmenopausal monozygotic twin pairs

MiRNAs are fine-tuning modifiers of skeletal muscle regulation, but knowledge of their hormonal control is lacking. We used a co-twin case-control study design, that is, monozygotic postmenopausal twin pairs discordant for estrogen-based hormone replacement therapy (HRT) to explore estrogen-dependent skeletal muscle regulation via miRNAs. MiRNA profiles were determined from vastus lateralis muscle of nine healthy 54-62-years-old monozygotic female twin pairs discordant for HRT (median 7 years). MCF-7 cells, human myoblast cultures and mouse muscle experiments were used to confirm estrogen's causal role on the expression of specific miRNAs, their target mRNAs and proteins and finally the act…

Strength, [corrected] endurance or combined training elicit diverse skeletal muscle myosin heavy chain isoform proportion but unaltered androgen receptor concentration in older men.

We investigated whether the myosin heavy chain (MyHC) proportion and androgen receptor (AR) concentration in skeletal muscle differ following 21 weeks of strength, endurance and combined training in untrained older men. Strength (S) and endurance (E) groups trained twice per week and combined (S+E) group trained four times per week (two strength and two endurance). Muscle biopsies were obtained before and after the training period from m. vastus lateralis (VL) and AR mRNA and protein concentration and MyHC proportion were determined. 1RM increased during the training period in S, S+E and E but the changes were greater in S and S+E than in E. Statistically significant increases were observed…

Volumetric changes of articular cartilage during stress relaxation in unconfined compression

The time-dependent lateral expansion and load relaxation of cartilage cylinders subjected to unconfined compression were simultaneously recorded. These measurements were used to (1) test the assumption of incompressibility for articular cartilage, (2) measure the Poisson's ratio of articular cartilage in compression and (3) investigate the relationship between stress relaxation and volumetric change. Mechanical tests were performed on fetal, calf, and adult humeral head articular cartilage. The instantaneous Poisson's ratio of adult cartilage was 0.49+/-0.08 (mean+S.D.), thus confirming the assumption of incompressibility for this tissue. The instantaneous Poisson's ratio was significantly …

Increased mRNAs for procollagens and key regulating enzymes in rat skeletal muscle following downhill running.

The purpose of the study was to investigate pre-translational regulation of collagen expression after a single bout of exercise. We analysed steady-state messenger ribonucleic acid (mRNA) levels for collagen types I, III and IV, alpha- and beta-subunits of prolyl 4-hydroxylase and lysyl oxidase (enzymes modifying procollagen chains), and enzyme activity of prolyl 4-hydroxylase from rat soleus muscle (MS) and the red parts of quadriceps femoris muscle (MQF) after 12 h and after 1, 2, 4, 7 and 14 days of downhill (-13.5 degrees ) treadmill running at a speed of 17 m.min-1 for 130 min. Histological and biochemical assays revealed exercise-induced muscle damage in MQF but not MS. Steady-state m…

Menopause and adipose tissue: miR-19a-3p is sensitive to hormonal replacement

Tissue-specific effects of 17 beta-estradiol are delivered via both estrogen receptors and microRNAs (miRs). Menopause is known to affect the whole-body fat distribution in women. This investigation aimed at identifying menopause-and hormone replacement therapy (HRT)-associated miR profiles and miR targets in subcutaneous abdominal adipose tissue and serum from the same women. A discovery phase using array technology was performed in 13 women, including monozygotic twin pairs discordant for HRT and premenopausal young controls. Seven miRs, expressed in both adipose tissue and serum, were selected for validation phase in 34 women from a different cohort. An age/menopause-related increase of …

Androgen receptors and testosterone in men—Effects of protein ingestion, resistance exercise and fiber type

The purpose of this study was to examine the impact of protein ingestion on circulating testosterone and muscle androgen receptor (AR) as well as on insulin-like growth factor-I (MGF and IGF-IEa) responses to a resistance exercise (RE) bout in (57-72 year) men. Protein (15 g whey) (n=9) or placebo (n=9) was consumed before and after a RE bout (5 sets of 10 repetition maximums), and vastus lateralis muscle biopsies were taken pre, 1 and 48 h post-RE. The protein ingestion blunted the RE-induced increase in serum free and total testosterone while the RE bout significantly increased muscle AR mRNA levels in older men (P<0.05). However, protein ingestion did not significantly affect AR mRNA or …

Catechol-O-Methyltransferase Gene Polymorphism Is Associated with Skeletal Muscle Properties in Older Women Alone and Together with Physical Activity

BackgroundMuscle strength declines on average by one percent annually from midlife on. In postmenopausal women this decrement coincides with a rapid decline in estrogen production. The genetics underlying the effects of estrogen on skeletal muscle remains unclear. In the present study, we examined whether polymorphisms within COMT and ESR1 are associated with muscle properties and assessed their interaction and their combined effects with physical activity.Methodology/principal findingsA cross-sectional data analysis was conducted with 434 63-76-year-old women from the population-based Finnish Twin Study on Aging. Body anthropometry, muscle cross-sectional area (mCSA), isometric hand grip a…

Hormone therapy is associated with better body composition and adipokine/glucose profiles

Objective: The aim of this study was to evaluate the possibility of preventing the metabolic health consequences of postmenopausal hypogonadism with the use of long-term hormone therapy (HT). Methods: We used a monozygotic co-twin control design including 10 twin pairs (aged 56-62 y) discordant for HT (duration of HT, 2-10 y). In addition, 14 premenopausal women (aged 29-35 y) who did not use HT were studied to evaluate the differences in metabolic health between the premenopausal and postmenopausal states. Body composition was determined, and waist-to-hip ratio was used as an estimate for fat distribution. Serum sex steroids, sex hormone-binding globulin, and serum lipid and glucose profil…

Validity and Reliability of a Single Question for Leisure-Time Physical Activity Assessment in Middle-Aged Women.

Purpose: To investigate the validity and test–retest reliability of a single seven-level scale physical activity assessment question (SR-PA L7) and its three-level categorization (SR-PA C3). Methods: The associations of SR-PA L7 and C3 with accelerometer-measured leisure-time physical activity (ACC-LTPA) and with the results of four different physical performance tests (6-min walk [n = 733], knee extension [n = 695], vertical jump [n = 731], and grip force [n = 780]) were investigated among women aged 47–55 years participating in the Estrogenic Regulation of Muscle Apoptosis study (n = 795). The reliability was studied using Spearman correlations with 4-month test–retest period (n = 152). R…

Human Achilles tendon glycation and function in diabetes

Diabetic patients have an increased risk of foot ulcers, and glycation of collagen may increase tissue stiffness. We hypothesized that the level of glycemic control (glycation) may affect Achilles tendon stiffness, which can influence gait pattern. We therefore investigated the relationship between collagen glycation, Achilles tendon stiffness parameters, and plantar pressure in poorly ( n = 22) and well ( n = 22) controlled diabetic patients, including healthy age-matched (45–70 yr) controls ( n = 11). There were no differences in any of the outcome parameters (collagen cross-linking or tendon stiffness) between patients with well-controlled and poorly controlled diabetes. The overall effe…

Hormone Replacement Therapy Associated White Blood Cell DNA Methylation and Gene Expression are Associated With Within-Pair Differences of Body Adiposity and Bone Mass.

The loss of estrogen during menopause causes changes in the female body, with wide-ranging effects on health. Estrogen-containing hormone replacement therapy (HRT) leads to a relief of typical menopausal symptoms, benefits bone and muscle health, and is associated with tissue-specific gene expression profiles. As gene expression is controlled by epigenetic factors (including DNA methylation), many of which are environmentally sensitive, it is plausible that at least part of the HRT-associated gene expression is due to changes in DNA methylation profile. We investigated genome-wide DNA methylation and gene expression patterns of white blood cells (WBCs) and their associations with body compo…

Recovery after Heavy Resistance Exercise and Skeletal Muscle Androgen Receptor and Insulin-Like Growth Factor-I Isoform Expression in Strength Trained Men

The effects of heavy resistance exercise on skeletal muscle androgen receptor (AR) protein concentration and mRNAs of AR, insulin-like growth factor-I (IGF)-IEa, and mechano growth factor (MGF) expression were examined from biopsies of vastus lateralis (VL) muscle before and 48 hours after heavy resistance exercise (5 × 10 repetition maximum [RM] leg press and 4 × 10RM squats) in 8 adult strength trained men. The present exercise induced an acute decrease in maximal isometric force and increased serum total testosterone (T) and free testosterone (FT) concentrations. During 2 recovery days, maximal isometric force and subjective perception of physical fitness remained significantly lowered, …

Impact of oral contraceptive use and menstrual phases on patellar tendon morphology, biochemical composition, and biomechanical properties in female athletes

Sex differences exist with regards to ligament and tendon injuries. Lower collagen synthesis has been observed in exercising women vs. men, and in users of oral contraceptives (OC) vs. nonusers, but it is unknown if OC will influence tendon biomechanics of women undergoing regular training. Thirty female athletes (handball players, 18–30 yr) were recruited: 15 long-term users of OC (7.0 ± 0.6 yr) and 15 nonusers (&gt;5 yr). Synchronized values of patellar tendon elongation (obtained by ultrasonography) and tendon force were sampled during ramped isometric knee extensor maximum voluntary contraction to estimate mechanical tendon properties. Furthermore, tendon cross-sectional area and lengt…

COL1A1 Sp1 polymorphism associates with bone density in early puberty.

Optimal acquisition of bone mass in puberty is a key determinant of the lifetime risk of osteoporosis and has a strong genetic basis. We investigated the relationship between the COL1A1 Sp1 polymorphism and BMD in early puberty, and how the genotypes relate to bone size and geometry as well as bone turnover and material properties in 247 10- to 13-year-old girls. Bone properties were measured using DXA, pQCT, and ultrasound. Also, serum P1NP, OC, B-ALP, and TRACP 5b were assessed. Our results showed that girls with the TT genotype had significantly lower BMC and BMD of the total body, lumbar spine, and proximal femur, as well as BUA at the calcaneus, than those with the GT and GG genotype. …

OGT and OGA expression in postmenopausal skeletal muscle associates with hormone replacement therapy and muscle cross-sectional area

Protein glycosylation via O-linked N-acetylglucosaminylation (O-GlcNAcylation) is an important post-translational regulatory mechanism mediated by O-GlcNAc transferase (OGT) and responsive to nutrients and stress. OGT attaches an O-GlcNAc moiety to proteins, while O-GlcNAcase (OGA) catalyzes O-GlcNAc removal. In skeletal muscle of experimental animals, prolonged increase in O-GlcNAcylation associates with age and muscle atrophy. Here we examined the effects of hormone replacement therapy (HRT) and power training (PT) on muscle OGT and OGA gene expression in postmenopausal women generally prone to age-related muscle weakness. In addition, the associations of OGT and OGA gene expressions with…

Effects of resistance training on expression of IGF-I splice variants in younger and older men.

Insulin-like growth factor-I (IGF-I) and its splice variants Insulin-like growth factor-I isoform Ea (IGF-IEa) and mechano growth factor (MGF) may play an important role in muscular adaptations to resistance training (RT) that may be modulated by ageing. It has been suggested that IGF-I induces cellular responses via AKT8 virus oncogene cellular homolog (Akt) and Extracellular signal-regulated kinase (Erk) signalling pathways. Therefore, resistance exercise-induced changes in skeletal muscle IGF-IEa and MGF messenger ribonucleic acid (mRNA), and MGF, Erk1/2, Akt and p70S6K protein expression were investigated before and after 21 weeks of RT in younger (YM, 20–34 yrs., n = 7) and older men (…

DIFFERENTIAL INFLUENCE OF PERIPHERAL AND SYSTEMIC SEX STEROIDS ON SKELETAL MUSCLE QUALITY IN PRE- AND POSTMENOPAUSAL WOMEN.

Aging is associated with gradual decline of skeletal muscle strength and mass often leading to diminished muscle quality. This phenomenon is known as sarcopenia and affects about 30% of the over 60-year-old population. Androgens act as anabolic agents regulating muscle mass and improving muscle performance. The role of female sex steroids as well as the ability of skeletal muscle tissue to locally produce sex steroids has been less extensively studied. We show that despite the extensive systemic deficit of sex steroid hormones in postmenopausal compared to premenopausal women, the hormone content of skeletal muscle does not follow the same trend. In contrast to the systemic levels, muscle t…

Effects of aging and life-long physical training on collagen in slow and fast skeletal muscle in rats. A morphometric and immuno-histochemical study.

Intramuscular collagen in a slow (m. soleus) and a fast (m. rectus femoris) skeletal muscle was studied by biochemical, morphometric, and immunohistochemical methods. Wistar white rats of 1, 4, 10, and 24 months were used as experimental animals. Our aim was to evaluate the effects of life-long physical training (treadmill running, 5 days a week for 1, 3, 9, and 23 months depending on the age attained). The biochemical concentration of collagen was higher in m. soleus than in m. rectus femoris and it increased in youth and in old age in m. soleus. The trained rats had higher concentrations of collagen than the untrained rats at 10 and 24 months. The morphometrically measured area-fractions …

Improved Bone Biomechanical Properties in Rats after Oral Xylitol Administration

The effects of 5, 10, and 20% dietary xylitol supplementations on the biomechanical properties, histological architecture, and the contents of collagen, pyridinoline, and deoxypyridinoline in long bones of rats were studied. Tibiae were used for the three-point bending test, and femurs were used for the torsion and loading test of the femoral neck. The 10 and 20% oral xylitol administrations caused a significant increase of tibial stress, femoral shear stress, and stress of the femoral neck as compared with the controls. Parallel, but not significant, effects were also seen in the 5% xylitol supplementation group. No significant differences in strain or Young's modulus of the tibiae were de…

Influence of Oral Contraceptive Use on Adaptations to Resistance Training

Introduction: The majority of young women use oral contraceptives (OCs). Use of OCs has been associated with lower myofibrillar protein and tendon collagen synthesis rates, but it is unknown whether OCs will limit the adaptive response of myotendinous tissue to resistance training. Design and Methods: Fourteen healthy untrained young regular OC users (24 +/- 1 years, fat% 32 +/- 1, 35 +/- 2 ml.min(-1).kg(-1)) and 14 NOC users (non-OC, controls) (24 +/- 1 years, fat% 32 +/- 2, 34 +/- 2 ml.min(-1).kg(-1)) performed a 10-week supervised lower extremity progressive resistance training program. Before and after the intervention biopsies from the vastus lateralis muscle and the patellar tendon we…

Muscular transcriptome in postmenopausal women with or without hormone replacement.

The loss of muscle mass and strength with aging is well characterized, but our knowledge of the molecular mechanisms underlying the development of sarcopenia remains incomplete. Although menopause is often accompanied with first signs of age-associated changes in muscle structure and function, the effects of hormone replacement therapy (HRT) or menopause-related decline in estrogen production in the muscles of postmenopausal women is not well understood. Furthermore the knowledge of the global transcriptional changes that take place in skeletal muscle in relation to estrogen status has thus far been completely lacking. We used a randomized double-blinded study design together with an explor…

Effects of 32-year leisure time physical activity discordance in twin pairs on health (TWINACTIVE study): aims, design and results for physical fitness.

AbstractThe physically active lifestyle is associated with low future morbidity and mortality, but the causality between physical activity and health is not always clear. As some inherited biological characteristics and childhood experiences may cause selection bias in observational studies, we sought to take them into account by identifying 16 twin pairs (7 MZ, 9 DZ, mean age 60 years) discordant for leisure time physical activity habits for thirty years. We conducted detailed health-related examinations among these twin pairs. Our main aims were to study the effects of physical activity and genes on fitness and body composition, with special reference to body fat compartments, metabolic s…

Hormone replacement therapy improves contractile function and myonuclear organization of single muscle fibres from postmenopausal monozygotic female twin pairs

Ageing is associated with a decline in muscle mass and strength leading to increased physical dependency in old age. Postmenopausal women experience a greater decline than men of similar age in parallel with the decrease in female sex steroid hormone production. We recruited six monozygous female twin pairs (55-59 years old) where only one twin pair was on hormone replacement therapy (HRT use = 7.8 ± 4.3 years) to investigate the association of HRT with the cytoplasmic volume supported by individual myonuclei (myonuclear domain (MND) size,) together with specific force at the single fibre level. HRT use was associated with a significantly smaller (∼27%; P < 0.05) mean MND size in muscle fib…

Declining Physical Performance Associates with Serum FasL, miR-21, and miR-146a in Aging Sprinters.

Aging is associated with systemic inflammation and cellular apoptosis accelerating physiological dysfunctions. Whether physically active way of life affects these associations is unclear. This study measured the levels of serum inflammatory and apoptotic molecules, their change over 10 years, and their associations with physical performance in sprint-trained male athletes. HsCRP, cell counts, HGB, FasL, miR-21, and miR-146a were measured cross-sectionally (n=67, 18–90 yrs) and serum FasL, miR-21, and miR-146a and their aging-related associations with physical performance were assessed over a 10-year follow-up (n=49, 50–90 yrs). The cross-sectional study showed positive age correlations for …

Effects of age and life-time physical training on fibre composition of slow and fast skeletal muscle in rats.

The effects of age and endurance training on muscle fibre characteristics were studied in a slow (m. soleus, MS) and in a fast (m. rectus femoris, MRF) skeletal muscle. Wistar rats at ages of 1, 2, 4, 10, and 24 months were used as experimental animals. The trained rats were put to run on a motor-driven treadmill 5 d/wk beginning from the age of 1 month. The body weights of the animals increased continuously throughout their lives. The muscle weights increased up to the age of 10 months, after which they tended to decrease. The trained adult rats had lower body weights as well as lower muscle weights than the untrained adult rats. The amount of the intramuscular lipid decreased with age, es…

Predicting the age at natural menopause in middle-aged women

Objective To predict the age at natural menopause (ANM). Methods Cox models with time-dependent covariates were utilized for ANM prediction using longitudinal data from 47 to 55-year-old women (n = 279) participating in the Estrogenic Regulation of Muscle Apoptosis study. The ANM was assessed retrospectively for 105 women using bleeding diaries. The predictors were chosen from the set of 32 covariates by using the lasso regression (model 1). Another easy-to-access model (model 2) was created by using a subset of 16 self-reported covariates. The predictive performance was quantified with c-indices and by studying the means and standard deviations of absolute errors (MAE ± SD) between the pre…

Do More Highly Organized Collagen Fibrils Increase Bone Mechanical Strength in Loss of Mineral Density After One-Year Running Training?

The aim of this study was to evaluate the effects of long-term running training on the structural properties of bone. Ten beagle dogs ran according to a strenuous progressive program (up to 40 km/day) for 1 year. At the end of the training program, there was a significant reduction in bone mineral density (up to 9.7%) in the vertebrae of the runner dogs as compared with 10 sedentary control dogs. Polarized light microscopy of the vertebral trabecular bone, however, displayed proportionally higher retardation values of the collagen network of the runner dogs than of the sedentary dogs, suggesting a reorganization in a more parallel manner in the collagen fibrils. The concentration and cross-…

Fracture Mechanics of Collagen Fibrils: Influence of Natural Cross-Links

AbstractTendons are important load-bearing structures, which are frequently injured in both sports and work. Type I collagen fibrils are the primary components of tendons and carry most of the mechanical loads experienced by the tissue, however, knowledge of how load is transmitted between and within fibrils is limited. The presence of covalent enzymatic cross-links between collagen molecules is an important factor that has been shown to influence mechanical behavior of the tendons. To improve our understanding of how molecular bonds translate into tendon mechanics, we used an atomic force microscopy technique to measure the mechanical behavior of individual collagen fibrils loaded to failu…

Physical Performance During the Menopausal Transition and the Role of Physical Activity

Abstract Background To examine longitudinal changes in physical performance during the menopausal transition and the role of physical activity (PA) in these changes. Methods Based on follicle-stimulating hormone levels and bleeding diaries, women (47–55 years) were classified as early (n = 89) and late perimenopausal (n = 143) and followed prospectively until postmenopausal status, with mean duration of 17.5 and 13.8 months, respectively. Physical performance was measured by handgrip force, knee extension torque, vertical jumping height, maximal walking speed, and 6-minute walking distance. Physical activity was self-reported and categorized as inactive, low, medium, and high. Longitudinal …

Global gene expression profiles in skeletal muscle of monozygotic female twins discordant for hormone replacement therapy

Aging is accompanied by inexorable loss of muscle tissue. One of the underlying causes for this is the massive change in the hormonal milieu of the body. The role of a female sex steroid – estrogen – in these processes is frequently neglected, although the rapid decline in its production coincides with a steep deterioration in muscle performance. We recruited 54- to 62-year-old monozygotic female twin pairs discordant for postmenopausal hormone replacement therapy (HRT, n = 11 pairs; HRT use 7.3 ± 3.7 years) from the Finnish Twin Cohort to investigate the association of long-term, estrogen-based HRT with skeletal muscle transcriptome. Pathway analysis of muscle transcript profiles revealed …

Collagen of slow twitch and fast twitch muscle fibres in different types of rat skeletal muscle

The appearance of collagen around individual fast twitch (FT) and slow twitch (ST) muscle fibres was investigated in skeletal muscles with different contractile properties using endurance trained and untrained rats as experimental animals. The collagenous connective tissue was analyzed by measuring hydroxyproline biochemically and by staining collagenous material histochemically in M. soleus (MS), M. rectus femoris (MRF), and M. gastrocnemius (MG). The concentration of hydroxyproline in the ST fibres dissected from MS (2.72 +/- 0.35 micrograms X mg-1 d.w.) was significantly higher than that of the FT fibres dissected from MRF (1.52 +/- 0.33 micrograms X mg-1 d.w.). Similarly, the concentrat…

The Older Finnish Twin Cohort : 45 Years of Follow-up

AbstractThe older Finnish Twin Cohort (FTC) was established in 1974. The baseline survey was in 1975, with two follow-up health surveys in 1981 and 1990. The fourth wave of assessments was done in three parts, with a questionnaire study of twins born during 1945–1957 in 2011–2012, while older twins were interviewed and screened for dementia in two time periods, between 1999 and 2007 for twins born before 1938 and between 2013 and 2017 for twins born in 1938–1944. The content of these wave 4 assessments is described and some initial results are described. In addition, we have invited twin-pairs, based on response to the cohortwide surveys, to participate in detailed in-person studies; these …

Physical performance in relation to menopause status and physical activity

Objective: The aim of this study was to examine differences in physical performance (muscle power, muscle strength, aerobic capacity, and walking speed) across menopausal stages and potential of leisure physical activity (PA) to modify the impact of menopause on physical performance. Methods: In this cross-sectional study, women aged 47 to 55 were randomly selected from the Finnish National Registry and categorized as premenopausal (n ¼ 233), perimenopausal (n ¼ 381), or postmenopausal (n ¼ 299) based on serum concentrations of follicle-stimulating hormone and bleeding diary. Physical performance was measured by knee extension force, handgrip force, vertical jumping height, maximal walking …

Enhanced prolylhydroxylase activity in the posterior annulus fibrosus of canine intervertebral discs following long-term running exercise

The effect of long-term excercise on the intervertebral disc collagen concentration (hydroxyproline), collagen-synthesizing enzymes (prolyl-4-hydroxylase, PH, and galactosyl-hydroxylysyl glucosyltransferase, GGT) and hydroxypyridinium crosslinks was studied in ten female beagle dogs. The dogs were run on a treadmill for 1 year starting at the age of 15 weeks. The daily running distance was gradually increased to 40km, which distance the dogs ran for the final 15 weeks. Ten untrained dogs from the same breeding colony served as controls. The nucleus pulposus and anterior and posterior halves of the annulus fibrosus of C2-3, T10-12, L4-5 disc segments were analysed. Crosslinks were measured f…

Metabolic health, menopause, and physical activity : a 4-year follow-up study

Background In women, metabolic health deteriorates after menopause, and the role of physical activity (PA) in mitigating the change is not completely understood. This study investigates the changes in indicators of metabolic health around menopause and evaluates whether PA modulates these changes. Methods Longitudinal data of 298 women aged 48–55 years at baseline participating in the ERMA and EsmiRs studies was used. Mean follow-up time was 3.8 (SD 0.1) years. Studied indicators of metabolic health were total and android fat mass, waist circumference, waist-to-hip ratio (WHR), systolic (SBP) and diastolic (DBP) blood pressure, blood glucose, triglycerides, serum total cholesterol, and high…

Lower strength of the human posterior patellar tendon seems unrelated to mature collagen cross-linking and fibril morphology

The human patellar tendon is frequently affected by tendinopathy, but the etiology of the condition is not established, although differential loading of the anterior and posterior tendon may be associated with the condition. We hypothesized that changes in fibril morphology and collagen cross-linking would parallel differences in material strength between the anterior and posterior tendon. Tendon fascicles were obtained from elective ACL surgery patients and tested micromechanically. Transmission electron microscopy was used to assess fibril morphology, and collagen cross-linking was determined by HPLC and calorimetry. Anterior fascicles were markedly stronger (peak stress: 54.3 ± 21.2 vs.…

Associations of physical performance and physical activity with mental well-being in middle-aged women

Abstract Background To investigate whether physical performance is independently of physical activity (PA) associated with positive and negative dimensions of mental well-being in middle-aged women. Methods Data were drawn from the Estrogenic Regulation of Muscle Apoptosis (ERMA) study in which women 47 to 55 years were randomly selected from the Finnish National Registry. They (n = 909) participated in measurements of physical performance (handgrip force, knee extension force, vertical jumping height, maximal walking speed, and six-minute walking distance). Both mental well-being (the Centre for Epidemiologic Studies Depression Scale, the International Positive and Negative Affect Schedule…

Micromechanical Properties and Collagen Composition of Ruptured Human Achilles Tendon

Background:The Achilles tendon is one of the strongest tendons in the human body, and yet it frequently ruptures, which is a substantial clinical problem. However, the cause of ruptures remains elusive.Hypothesis:Ruptured human Achilles tendon displays inferior biomechanical properties and altered collagen composition compared with noninjured tendon.Study Design:Controlled laboratory study.Methods:Biopsy specimens were obtained at the rupture site and the noninjured part of the tendon (internal controls) in 17 patients with acute Achilles tendon rupture. Age- and weight-matched human cadaveric Achilles tendons (external controls) were also obtained. Tendon samples were tested micromechanica…

Leisure-time physical activity and high-risk fat: a longitudinal population-based twin study.

Exercise is thought to reduce high-risk body fat, but intervention studies are frequently limited by short follow-ups and observational studies by genetic selection. Therefore, we studied the effects of a physically inactive vs active lifestyle on high-risk (visceral, liver and intramuscular) fat in twin pairs discordant for leisure-time physical activity habits for over 30 years.A longitudinal population-based twin study.Sixteen middle-aged (50-74 years) same-sex twin pairs (seven monozygotic (MZ), nine dizygotic (DZ)) with long-term discordance for physical activity habits were comprehensively identified from the Finnish Twin Cohort (TWINACTIVE study). Discordance was initially defined in…

Additional file 1 of Blood and skeletal muscle ageing determined by epigenetic clocks and their associations with physical activity and functioning

Additional file 1: Within-pair correlations in age acceleration in blood and in muscle. Additional file 2: Associations between DNAmAge age acceleration estimates and body composition and physical activity in blood. Additional file 3: Sensitivity analyses related to twin pair discordance in body mass index.

Adolescent Sport Participation and Age at Menarche in Relation to Midlife Body Composition, Bone Mineral Density, Fitness, and Physical Activity

This study aimed to investigate the associations of competitive sport participation in adolescence and age at menarche (AAM) with body composition, femoral neck bone mineral density (BMD), physical performance, and physical activity (PA) in middle-aged women. 1098 women aged 47&ndash

Aging and systemic hormonal status affects the circulating miR-21, miR-146a and FasL levels

MicroRNAs are small molecules, found in all cell types and body fluids, which most commonly affect negatively to gene expressions by translational repression. Their role in various physiological conditions and diseases has been emphasized during the last twenty years. In our recent studies with postmenopausal monozygotic twin sisters (n=11), we have investigated how different systemic hormonal status affects the levels of specific circulating microRNAs and other molecules related to inflammation and apoptosis, both processes associated with aging. Our results have shown that the systemic levels of miR-21, miR-146a and Fas ligand are lower within the postmenopausal women who are using estrog…

Resistance exercise with whey protein ingestion affects mTOR signaling pathway and myostatin in men.

Signaling pathways sense local and systemic signals and regulate muscle hypertrophy. The effects of whey protein ingestion on acute and long-term signaling responses of resistance exercise are not well known. Previously untrained young men were randomized into protein ( n = 9), placebo ( n = 9), and control ( n = 11) groups. Vastus lateralis (VL) muscle biopsies were taken before and 1 h and 48 h after a leg press of 5 × 10 repetitions [resistance exercise (RE)] and after 21 wk (2 times per week) of resistance training (RT). Protein (15 g of whey) or nonenergetic placebo was ingested before and after a single RE bout and each RE workout throughout the RT. The protein group increased its bo…

Additional file 1 of Blood and skeletal muscle ageing determined by epigenetic clocks and their associations with physical activity and functioning

Additional file 1: Within-pair correlations in age acceleration in blood and in muscle. Additional file 2: Associations between DNAmAge age acceleration estimates and body composition and physical activity in blood. Additional file 3: Sensitivity analyses related to twin pair discordance in body mass index.

Effects of combined hormone replacement therapy or its effective agents on the IGF-1 pathway in skeletal muscle.

Objectives To investigate the effects of combined hormone replacement therapy (HRT) and its effective agents on the IGF-1 signaling pathway. Design and methods To examine the effects of HRT on skeletal muscle in vivo, we utilized pre- and post-intervention samples from a randomized double blinded trial with 50–57-year-old women. The intervention included the year-long use of either HRT preparation (2 mg 17β-estradiol, E2; 1 mg norethisterone acetate, NETA, n = 10) or placebo (CO, n = 9). Microarray technology and quantitative PCR (qPCR) were used to study the expression of insulin-like growth factor I (IGF-1) and its splice variants as well as IGF-1 receptor, Akt1, mTOR, FOXO1, FOXO3, atrog…

Hormone replacement therapy improves contractile function and myonuclear organization of single fibres from postmenopausal monozygotic female twin pairs.

Ageing is associated with a decline in muscle mass and strength leading to increased physical dependency in old age. Postmenopausal women experience a greater decline than men of similar age in parallel with the decrease in female sex steroid hormone production. We recruited six monozygous female twin pairs (55–59 years old) where only one twin pair was on hormone replacement therapy (HRT use = 7.8 ± 4.3 years) to investigate the association of HRT with the cytoplasmic volume supported by individual myonuclei (myonuclear domain (MND) size,) together with specific force at the single fibre level. HRT use was associated with a significantly smaller (∼27%; P < 0.05) mean MND size in muscle fib…

Changes in collagen cross-linking of articular cartilage are revealed by spectral reflectance imaging

Excessive cross-linking of collagen during aging may contribute to degeneration of articular cartilage. Traditionally, the amount of cross-links is derived by using destructive high-performance liquid chromatography (HPLC). However, a sensitive, non-destructive method could help to evaluate tissue integrity, including cross-links. We increased collagen cross-linking in bovine articular cartilage by controlled threose incubation. During the incubation, optical spectral reflectance images of the samples were captured and related to HPLC results using regression analysis. Significant correlations with reflectance and cross-links were observed. When further developed the optical method may enab…

Type IV collagen and laminin in slow and fast skeletal muscle in rats--effects of age and life-time endurance training.

The changes in the biochemical composition of basement membrane (BM) in slow-twitch (m. soleus, MS) and fast-twitch (m. rectus femoris, MRF) skeletal muscles of rats were studied during aging and life-time endurance training (treadmill running). The concentrations of the 7S domain of type IV collagen and of the P2 fragment of laminin were determined with radioimmunoassays in the muscles of rats aged 1, 2, 4, 10, and 24 months. The concentration of type IV collagen was higher in MS than in MRF and increased significantly with age. At older ages, the concentration tended to be higher in the MS of trained than untrained rats. The concentration of laminin was significantly higher in MRF than in…

Aging and serum exomiR content in women-effects of estrogenic hormone replacement therapy.

AbstractExosomes participate in intercellular messaging by transporting bioactive lipid-, protein- and RNA-molecules and -complexes. The contents of the exosomes reflect the physiological status of an individual making exosomes promising targets for biomarker analyses. In the present study we extracted exosome microRNAs (exomiRs) from serum samples of premenopausal women (n = 8) and monozygotic postmenopausal twins (n = 10 female pairs), discordant for the use of estrogenic hormone replacement therapy (HRT), in order to see whether the age or/and the use of HRT associates with exomiR content. A total of 241 exomiRs were detected by next generation sequencing, 10 showing age, 14 HRT and 10 a…

Female reproductive factors are associated with objectively measured physical activity in middle-aged women

Physical activity improves health and may delay the onset of several chronic diseases. For women in particular, the rate of these diseases accelerates at middle age; therefore it is important to identify the determinants of health-enhancing physical activity during midlife in this population. In this study, we focused on determinants that are unique to the female sex, such as childbearing and menopause. The main objective was to characterize the level of physical activity and differences between active and inactive middle-aged Finnish women. In addition, we examined the association of physical activity with female reproductive factors at midlife. The study population consisted of 647 women …

Estrogen Regulates the Satellite Cell Compartment in Females

SUMMARYSkeletal muscle mass, strength, and regenerative capacity decline with age, with many measures showing greater deterioration in females about the time estrogen levels decrease at menopause. Here we show that maintenance of muscle stem cells, satellite cells, as well as self-renewal and differentiation into muscle fibers, are severely compromised by estrogen deficiency. Mechanistically, by hormone replacement, use of a selective estrogen-receptor modulator (bazedoxifene), and conditional estrogen receptor knockout, we implicate 17β-estradiol and satellite cell expression of estrogen receptorα(ERα) and show that estrogen signaling through this receptor is necessary to prevent apoptosis…

Heavy resistance exercise training and skeletal muscle androgen receptor expression in younger and older men

Effects of heavy resistance exercise on serum testosterone and skeletal muscle androgen receptor (AR) concentrations were examined before and after a 21-week resistance training period. Seven healthy untrained young adult men (YT) and ten controls (YC) as well as ten older men (OT) and eight controls (OC) volunteered as subjects. Heavy resistance exercise bouts (5 × 10 RM leg presses) were performed before and after the training period. Muscle biopsies were obtained before and 1h and 48 h after the resistance exercise bouts from m.vastus lateralis (VL) to determine cross-sectional area of muscle fibers (fCSA) and AR mRNA expression and protein concentrations. No changes were observed in YC …

Mechanical Properties of Human Patellar Tendon at the Hierarchical levels of Tendon and Fibril

Tendons are strong hierarchical structures, but how tensile forces are transmitted between different levels remains incompletely understood. Collagen fibrils are thought to be primary determinants of whole tendon properties, and therefore we hypothesized that the whole human patellar tendon and its distinct collagen fibrils would display similar mechanical properties. Human patellar tendons ( n = 5) were mechanically tested in vivo by ultrasonography. Biopsies were obtained from each tendon, and individual collagen fibrils were dissected and tested mechanically by atomic force microscopy. The Young's modulus was 2.0 ± 0.5 GPa, and the toe region reached 3.3 ± 1.9% strain in whole patellar …

Age- and training-related changes in the collagen metabolism of rat skeletal muscle

The effects of ageing and life-long endurance training on the collagen metabolism of skeletal muscle were evaluated in a longitudinal study. Wistar rats performed treadmill running 5 days a week for 2 years. The activities of collagen biosynthesis enzymes, prolyl-4-hydroxylase and galactosylhydroxylysyl glucosyltransferase, were highest in the muscles of the youngest animals, decreased up to the age of 2 months and from then on remained virtually unchanged. The enzyme activity in young animals was higher in the slow collagenous soleus muscle than in the rectus femoris muscle. The enzyme activity in the soleus muscle was higher for older trained rats than older untrained rats. The relative p…

Computed tomography detects changes in contrast agent diffusion after collagen cross-linking typical to natural aging of articular cartilage

SummaryObjectiveThe effect of threose-induced collagen cross-linking on the mechanical and diffusive properties of cartilage was investigated in vitro. In particular, we investigated the potential of Contrast Enhanced Computed Tomography (CECT) to detect changes in articular cartilage after increased collagen cross-linking, which is an age-related phenomenon.MethodsOsteochondral plugs (Ø=6.0mm, n=28) were prepared from intact bovine patellae (n=7). Two of the four adjacent samples, prepared from each patella, were treated with threose to increase the collagen cross-linking, while the other two specimen served as paired controls. One sample pair was mechanically tested and then mechanically …

Intramuscular sex steroid hormones are associated with skeletal muscle strength and power in women with different hormonal status

International audience; Estrogen (E2)-responsive peripheral tissues, such as skeletal muscle, may suffer from hormone deficiency after menopause potentially contributing to the aging of muscle. However, recently E2 was shown to be synthesized by muscle and its systemic and intramuscular hormone levels are unequal. The objective of the study was to examine the association between intramuscular steroid hormones and muscle characteristics in premenopausal women (n = 8) and in postmenopausal monozygotic twin sister pairs (n = 16 co-twins from eight pairs) discordant for the use of E2-based hormone replacement. Isometric skeletal muscle strength was assessed by measuring knee extension strength.…

Regulation of synthesis of fibrillar collagens in rat skeletal muscle during immobilization in shortened and lengthened positions

Immobilization has been shown to cause muscle atrophy and decreased total collagen synthesis in skeletal muscle. These changes can be counteracted by stretch. The purpose of this study was to find out the early effects of immobilization in shortened and lengthened positions on expression of type I and III collagen at pre- and post-translational level. The mRNA levels of type I and III collagen, prolyl 4-hydroxylase activity, total collagen concentration and the proportions of type I and III collagens were analysed in soleus (SOL), gastrocnemius (GM), extensor digitorum longus and tibialis anterior (TA) muscles during immobilization in shortened and lengthened positions for 1, 3 and 7 days. …

Nondestructive fluorescence-based quantification of threose-induced collagen cross-linking in bovine articular cartilage.

Extensive collagen cross-linking affects the mechanical competence of articular cartilage: it can make the cartilage stiffer and more brittle. The concentrations of the best known cross-links, pyridinoline and pentosidine, can be accurately determined by destructive high-performance liquid chromatography (HPLC). We explore a nondestructive evaluation of cross-linking by using the intrinsic fluorescence of the intact cartilage. Articular cartilage samples from bovine knee joints were incubated in threose solution for 40 and 100 h to increase the collagen cross-linking. Control samples without threose were also prepared. Excitation-emission matrices at wavelengths of 220 to 950 nm were acquir…

Combination of hormone replacement therapy and high physical activity is associated with differences in Achilles tendon size in monozygotic female twin pairs.

Estrogen concentration has been suggested to play a role in tendon abnormalities and injury. In physically active postmenopausal women, hormone replacement therapy (HRT) has been suggested to decrease tendon diameter. We hypothesized that HRT use and physical activity are associated with Achilles tendon size and tissue structure. The study applied cotwin analysis of fourteen 54- to 62-yr-old identical female twin pairs with current discordance for HRT use for an average of 7 yr. Achilles tendon thickness and cross-sectional areas were determined by ultrasonography, and tendon structural organization was analyzed from the images using linear discriminant analysis (LDA). Maximal voluntary and…

Long-term Leisure-time Physical Activity and Serum Metabolome

Background— Long-term physical inactivity seems to cause many health problems. We studied whether persistent physical activity compared with inactivity has a global effect on serum metabolome toward reduced cardiometabolic disease risk. Methods and Results— Sixteen same-sex twin pairs (mean age, 60 years) were selected from a cohort of twin pairs on the basis of their &gt;30-year discordance for physical activity. Persistently (≥5 years) active and inactive groups in 3 population-based cohorts (mean ages, 31–52 years) were also studied (1037 age- and sex-matched pairs). Serum metabolome was quantified by nuclear magnetic resonance spectroscopy. We used permutation analysis to estimate the …

Accelerometer-measured and self-reported physical activity in relation to extraversion and neuroticism: a cross-sectional analysis of two studies

Background Personality reflects relatively stable and pervasive tendencies in feeling, thinking and behaving. While previous studies have found higher extraversion and lower neuroticism to be linked to higher self-reported physical activity levels, larger studies using accelerometer-measured physical activity are lacking. This study investigated the cross-sectional associations of extraversion and neuroticism with both accelerometer-measured and self-reported physical activity and the role of these personality traits in possible discrepancies between these two measures of physical activity among Finnish adults. Methods Two community-dwelling samples were used in this study: a) 47–55-yr-old …

Global gene expression profiles in skeletal muscle of monozygotic female twins discordant for hormone replacement therapy

Summary Aging is accompanied by inexorable loss of muscle tissue. One of the underlying causes for this is the massive change in the hormonal milieu of the body. The role of a female sex steroid – estrogen – in these processes is frequently neglected, although the rapid decline in its production coincides with a steep deterioration in muscle performance. We recruited 54- to 62-year-old monozygotic female twin pairs discordant for postmenopausal hormone replacement therapy (HRT, n = 11 pairs; HRT use 7.3 ± 3.7 years) from the Finnish Twin Cohort to investigate the association of long-term, estrogen-based HRT with skeletal muscle transcriptome. Pathway analysis of muscle transcript profiles r…

Power training and postmenopausal hormone therapy affect transcriptional control of specific co-regulated gene clusters in skeletal muscle

At the moment, there is no clear molecular explanation for the steeper decline in muscle performance after menopause or the mechanisms of counteractive treatments. The goal of this genome-wide study was to identify the genes and gene clusters through which power training (PT) comprising jumping activities or estrogen containing hormone replacement therapy (HRT) may affect skeletal muscle properties after menopause. We used musculus vastus lateralis samples from early stage postmenopausal (50–57 years old) women participating in a yearlong randomized double-blind placebo-controlled trial with PT and HRT interventions. Using microarray platform with over 24,000 probes, we identified 665 diffe…

Menopause modulates the circulating metabolome: evidence from a prospective cohort study

Abstract Aims We studied the changes in the circulating metabolome and their relation to the menopausal hormonal shift in 17β-oestradiol and follicle-stimulating hormone levels among women transitioning from perimenopause to early postmenopause. Methods and results We analysed longitudinal data from 218 Finnish women, 35 of whom started menopausal hormone therapy during the study. The menopausal transition was monitored with menstrual diaries and serum hormone measurements. The median follow-up was 14 months (interquartile range: 8–20). Serum metabolites were quantified with targeted nuclear magnetic resonance metabolomics. The model results were adjusted for age, follow-up duration, educat…

Corticosteroid injections, eccentric decline squat training and heavy slow resistance training in patellar tendinopathy.

Udgivelsesdato: Sep-28 A randomized-controlled single-blind trial was conducted to investigate the clinical, structural and functional effects of peritendinous corticosteroid injections (CORT), eccentric decline squat training (ECC) and heavy slow resistance training (HSR) in patellar tendinopathy. Thirty-nine male patients were randomized to CORT, ECC or HSR for 12 weeks. We assessed function and symptoms (VISA-p questionnaire), tendon pain during activity (VAS), treatment satisfaction, tendon swelling, tendon vascularization, tendon mechanical properties and collagen crosslink properties. Assessments were made at 0 weeks, 12 weeks and at follow-up (half-year). All groups improved in VISA-…

Association Between Exercise and Pubertal BMD Is Modulated by Estrogen Receptor α Genotype

Genetic and environmental factors contribute to bone mass, but the ways they interact remain poorly understood. This study of 245 pre- and early pubertal girls found that the PvuII polymorphism in the ER- gene modulates the effect of exercise on BMD at loaded bone sites. Introduction: Impaired achievement of bone mass at puberty is an important risk factor for the development of osteoporosis in later life. Genetic, as well as environmental, factors contribute to bone mass, but the ways they interact with each other remain poorly understood. Materials and Methods: We investigated the interaction between a PvuII polymorphism at the ER- gene and physical activity (PA) on the modulation of bone…

Diffusion of ionic and non-ionic contrast agents in articular cartilage with increased cross-linking--contribution of steric and electrostatic effects.

Abstract Objective To investigate the effect of threose-induced collagen cross-linking on diffusion of ionic and non-ionic contrast agents in articular cartilage. Design Osteochondral plugs (O=6mm) were prepared from bovine patellae and divided into two groups according to the contrast agent to be used in contrast enhanced computed tomography (CECT) imaging: (I) anionic ioxaglate and (II) non-ionic iodixanol. The groups I and II contained 7 and 6 sample pairs, respectively. One of the paired samples served as a reference while the other was treated with threose to induce collagen cross-linking. The equilibrium partitioning of the contrast agents was imaged after 24h of immersion. Fixed char…

Genetics of maximal walking speed and skeletal muscle characteristics in older women.

AbstractThe aim of this study was to examine whether maximal walking speed, maximal isometric muscle strength, leg extensor power and lower leg muscle cross-sectional area (CSA) shared a genetic effect in common. In addition, we wanted to identify the chromosomal areas linked to maximal walking speed and these muscle characteristics and also investigate whether maximal walking speed and these three skeletal muscle characteristics are regulated by the same chromosomal areas. We studied 217 monozygotic (MZ) and dizygotic (DZ) female twin pairs aged 66 to 75 years in the Finnish Twin Study on Aging study. The DZ pairs (94) were genotyped for 397 microsatellite markers in 22 autosomes and X-chr…

Menopausal symptoms and cardiometabolic risk factors in middle-aged women : A cross-sectional and longitudinal study with 4-year follow-up

Objective To study associations of menopausal symptoms with cardiometabolic risk factors. Study design A cross-sectional and longitudinal study of a representative population sample of 1393 women aged 47–55 years with a sub-sample of 298 followed for four years. The numbers of vasomotor, psychological, somatic or pain, and urogenital menopausal symptoms were ascertained at baseline through self-report. Their associations with cardiometabolic risk factors were studied using linear regression and linear mixed-effect models. Models were adjusted for age, menopausal status, body mass index, the use of hormonal preparations, education, smoking, and alcohol consumption. Main outcome measures Card…

The glycosyltransferase activities of lysyl hydroxylase 3 (LH3) in the extracellular space are important for cell growth and viability.

Abstract Lysyl hydroxylase (LH) isoform 3 is a post-translational enzyme possessing LH, collagen galactosyltransferase (GT) and glucosyltransferase (GGT) activities. We have demonstrated that LH3 is found not only intracellularly, but also on the cell surface and in the extracellular space, suggesting additional functions for LH3. Here we show that the targeted disruption of LH3 by siRNA causes a marked reduction of both glycosyltransferase activities, and the overexpression of LH3 in HT-1080 cells increases hydroxylation of lysyl residues and the subsequent galactosylation and glucosylation of hydroxylysyl residues. These data confirm the multi-functionality of LH3 in cells. Furthermore, t…

Estrogenic regulation of skeletal muscle proteome : a study of premenopausal women and postmenopausal MZ cotwins discordant for hormonal therapy

Female middle age is characterized by a decline in skeletal muscle mass and performance, predisposing women to sarcopenia, functional limitations, and metabolic dysfunction as they age. Menopausal loss of ovarian function leading to low circulating level of 17b-estradiol has been suggested as a contributing factor to aging-related muscle deterioration. However, the underlying molecular mechanisms remain largely unknown and thus far androgens have been considered as a major anabolic hormone for skeletal muscle. We utilized muscle samples from 24 pre- and postmenopausal women to establish proteome-wide profiles, associated with the difference in age (30–34 years old vs. 54– 62 years old), men…

Influence of long-term postmenopausal hormone-replacement therapy on estimated structural bone strength: A study in discordant monozygotic twins

Although postmenopausal hormone-replacement therapy (HRT) is known to prevent fractures, knowledge on the influence of long-term HRT on bone strength and its determinants other than areal bone mineral density is scarce. This study used a genetically controlled design with 24 monozygotic female twin pairs aged 54 to 72 years in which one cotwin was using HRT (mean duration 8 years) and the other had never used HRT. Estimated bone strength, cross-sectional area, volumetric bone mineral density, bone mineral mass, and cross-sectional density and mass distributions were assessed in the tibial shaft, distal tibia, and distal radius with peripheral computed tomography (pQCT). In the tibial shaft,…

Circulating miR-21, miR-146a and Fas ligand respond to postmenopausal estrogen-based hormone replacement therapy--a study with monozygotic twin pairs.

Biological aging is associated with physiological deteriorations and its’ remodeling, which are partly due to changes in the hormonal profile. MicroRNAs are known to post-transcriptionally regulate various cellular processes associated with cell senescence; differentiation, replication and apoptosis. Measured from the serum, microRNAs have the potential to serve as noninvasive markers for diagnostics/prognostics and therapeutic targets. We analysed the association of estrogen-based hormone replacement therapy (HRT) with selected microRNAs and inflammation markers from the serum, leukocytes and muscle tissue biopsy samples obtained from 54-62 year-old postmenopausal monozygotic twins (n=11 p…

Influence of long-term postmenopausal hormone replacement therapy on estimated structural bone strength: A study in discordant monozygotic twins.

Although postmenopausal hormone-replacement therapy (HRT) is known to prevent fractures, knowledge on the influence of long-term HRT on bone strength and its determinants other than areal bone mineral density is scarce. This study used a genetically controlled design with 24 monozygotic female twin pairs aged 54 to 72 years in which one cotwin was using HRT (mean duration 8 years) and the other had never used HRT. Estimated bone strength, cross-sectional area, volumetric bone mineral density, bone mineral mass, and cross-sectional density and mass distributions were assessed in the tibial shaft, distal tibia, and distal radius with peripheral computed tomography (pQCT). In the tibial shaft,…

Menopausal Status and Physical Activity Are Independently Associated With Cardiovascular Risk Factors of Healthy Middle-Aged Women: Cross-Sectional and Longitudinal Evidence

Cardiovascular disease (CVD) is the primary cause of mortality in women in developed countries. CVD risk rises with age, yet for women there is a rapid increase in CVD risk that occurs after the onset of menopause. This observation suggests the presence of factors in the middle-aged women that accelerate the progression of CVD independent of chronological aging. Leisure time physical activity (LTPA) is a well-established protective factor against CVD. However, its role in attenuating atherogenic lipid profile changes and CVD risk in post-menopausal women has not been well-established. The present study is part of the Estrogenic Regulation of Muscle Apoptosis (ERMA) study, a population-based…

Synthesis and degradation of type IV collagen in rat skeletal muscle during immobilization in shortened and lengthened positions

Aim:  Type IV collagen is a major protein in basement membranes surrounding and supporting skeletal muscle cells. In the present study, we tested the hypotheses that immobilization down-regulates synthesis and up-regulates degradation of type IV collagen in skeletal muscle. Methods:  mRNA level and concentration of type IV collagen as well as mRNA levels and activities of proteins involved in its degradation were analysed from soleus (SOL), gastrocnemius (GAS) and extensor digitorum longus muscles after immobilization in shortened and lengthened positions for 1, 3 and 7 days. Results:  Following immobilization, type IV collagen mRNA level was decreased in SOL and GAS suggesting down-regulat…

Acute exercise induced changes in rat skeletal muscle mRNAs and proteins regulating type IV collagen content

This experiment tested the hypothesis that running-induced damage to rat skeletal muscle causes changes in synthesis and degradation of basement membrane type IV collagen and to proteins regulating its degradation. Samples from soleus muscle and red and white parts of quadriceps femoris muscle (MQF) were collected 6 h or 1, 2, 4, or 7 days after downhill running. Increased muscle β-glucuronidase activity indicated greater muscle damage in the red part of MQF than in the white part of MQF or soleus. In the red part of MQF, type IV collagen expression was upregulated at the pretranslational level and the protein concentration decreased, whereas matrix metalloproteinase-2 (MMP-2), a protein th…

Effects of military training on plasma amino acid concentrations and their associations with overreaching.

Amino acids are thought to have a key role in the processes contributing to overreaching development through their metabolic properties and neuronal functions. In the present study, the effects of 10-week military training on the concentrations of 19 amino acids were investigated. Plasma amino acid concentrations were measured at rest from 53 healthy male conscripts on weeks 1, 4, 7, and 9 of their military service. Conscripts were classified as overreached and non-overreached. Overreaching classification was based on fulfilling at least three of five criteria: greater than 5% decrease in maximal oxygen uptake, increased rating perceived exertion (RPE), and decreased lactate-RPE ratio in s…

Relation of PvuII site polymorphism in the COL1A2 gene to the risk of fractures in prepubertal Finnish girls.

Genetic susceptibility to fractures may be detectable in early childhood. We evaluated the associations between the polymorphic PvuII site of the COL1A2 gene and bone properties assessed by different modalities (dual-energy X-ray absorptiometry; peripheral quantitative computed tomography; gel coupling scanning quantitative ultrasonometry; ultrasound bone sonometry), bone turnover markers, and the occurrence of fractures in 244 prepubertal Finnish girls. Tanner stage and physical characteristics did not differ significantly among girls with different COL1A2 genotypes. The polymorphism was not significantly associated with different bone properties or any of the bone turnover markers when gi…

Intramuscular Extracellular Matrix: Complex Environment of Muscle Cells

KOVANEN, V. Intramuscular extracellular matrix: Complex environment of muscle cells. Exerc. Sport Sci. Rev., Vol. 30, No. 1, pp 20–25, 2002. Different collagen types among other extracellular matrix molecules, remodeling of the extracellular matrix with the aid of matrix metalloproteinases, and inte

Infrared microspectroscopic determination of collagen cross-links in articular cartilage

Collagen forms an organized network in articular cartilage to give tensile stiffness to the tissue. Due to its long half-life, collagen is susceptible to cross-links caused by advanced glycation end-products. The current standard method for determination of cross-link concentrations in tissues is the destructive high-performance liquid chromatography (HPLC). The aim of this study was to analyze the cross-link concentrations nondestructively from standard unstained histological articular cartilage sections by using Fourier transform infrared (FTIR) microspectroscopy. Half of the bovine articular cartilage samples ( n = 27 ) were treated with threose to increase the collagen cross-linking whi…

Physical Activity, Fitness, Glucose Homeostasis, and Brain Morphology in Twins

The main aim of the present study (FITFATTWIN) was to investigate how physical activity level is associated with body composition, glucose homeostasis, and brain morphology in young adult male monozygotic twin pairs discordant for physical activity.From a population-based twin cohort, we systematically selected 10 young adult male monozygotic twin pairs (age range, 32-36 yr) discordant for leisure time physical activity during the past 3 yr. On the basis of interviews, we calculated a mean sum index for leisure time and commuting activity during the past 3 yr (3-yr LTMET index expressed as MET-hours per day). We conducted extensive measurements on body composition (including fat percentage …

Muscle and bone mass in middle‐aged women : role of menopausal status and physical activity

Background. Women experience drastic hormonal changes during midlife due to the menopausal transition. Menopausal hormonal changes are known to lead to bone loss and potentially also to loss of lean mass. The loss of muscle and bone tissue coincide due to the functional relationship and interaction between these tissues. If and how physical activity counteracts deterioration in muscle and bone during the menopausal transition remains partly unresolved. This study investigated differences between premenopausal, early perimenopausal, late perimenopausal, and postmenopausal women in appendicular lean mass (ALM), appendicular lean mass index (ALMI), femoral neck bone mineral density (BMD) and T…

Effects of strength and endurance training on muscle fibrecharacteristics in elderly women

The effects of 18 weeks' intensive strength and endurance training on fibre characteristics of the vastus lateralis muscle were studied in 76- to 78-year-old women. Type I and type IIa fibres constituted over 90% of the cell population and were almost equally represented. No changes were observed in the proportions of the different fibre types. When comparing the baseline and the 18-week measurements within the groups, the strength group showed a mean increase of 34% (P = 0.028) in mean type I fibre area. The frequency histograms showed an increased proportion of larger type I fibres after strength training and a decreased proportion of smaller type IIa fibres after endurance training. In t…

Differential influence of peripheral and systemic sex steroids on skeletal muscle quality in pre- and postmenopausal women

Aging is associated with gradual decline of skeletal muscle strength and mass often leading to diminished muscle quality. This phenomenon is known as sarcopenia and affects about 30% of the over 60-year-old population. Androgens act as anabolic agents regulating muscle mass and improving muscle performance. The role of female sex steroids as well as the ability of skeletal muscle tissue to locally produce sex steroids has been less extensively studied. We show that despite the extensive systemic deficit of sex steroid hormones in postmenopausal compared to premenopausal women, the hormone content of skeletal muscle does not follow the same trend. In contrast to the systemic levels, muscle t…

Postmenopausal hormone replacement therapy modifies skeletal muscle composition and function: a study with monozygotic twin pairs

We investigated whether long-term hormone replacement therapy (HRT) is associated with mobility and lower limb muscle performance and composition in postmenopausal women. Fifteen 54- to 62-yr-old monozygotic female twin pairs discordant for HRT were recruited from the Finnish Twin Cohort. Habitual (HWS) and maximal (MWS) walking speeds over 10 m, thigh muscle composition, lower body muscle power assessed as vertical jumping height, and maximal isometric hand grip and knee extension strengths were measured. Intrapair differences (IPD%) with 95% confidence intervals (CI) were calculated. The mean duration of HRT use was 6.9 ± 4.1 yr. MWS was on average 7% (0.9 to 13.1%, P = 0.019) and muscle…

Physical Exercise Increases mRNA Levels of Fibrillar Collagen Types I and Iii and α-Subunit of Prolyl 4-Hydroxylase in Rat Skeletal Muscle

The influence of physical activity during youth on structural and functional properties of the Achilles tendon

Achilles tendinopathy is a highly prevalent sports injury. Animal studies show a growth response in tendons in response to loading in the immature phase but not after puberty maturation. The aim of this investigation was to examine the structural and material properties in long distance runners who were either physically active (HAY) or inactive (LAY) in young age. Twelve men in HAY group and eight men in LAY group participated. Structural, functional, and biochemical properties of Achilles tendon were estimated from magnetic resonance imaging, ultrasound video recordings, mechanical tests, and tendon biopsies, respectively. There was no difference between the groups with respect to tendon …

Postexercise myostatin and activin IIb mRNA levels: effects of strength training.

ABSTRACTHULMI, J. J., J. P. AHTIAINEN, T. KAASALAINEN, E. PO¨LLA¨NEN, K. HA¨KKINEN, M. ALEN, H. SELA¨NNE, V. KOVANEN,and A. A. MERO. Postexercise Myostatin and Activin IIb mRNA Levels: Effects of Strength Training. Med. Sci. Sports Exerc., Vol.39, No. 2, pp. 289–297, 2007. Purpose: Muscle hypertrophy is likely to result from the cumulative effects of repeated bouts ofresistance exercise (RE) on postexercise molecular responses. Therefore, we determined muscle growth- and regeneration-relatedmRNA expression in response to a single RE bout both before and after a strength-training (ST) period. By means of this novellongitudinal setting, we examined whether postexercise gene expression at the …

Total and regional body adiposity increases during menopause : evidence from a follow‐up study

For women, menopausal transition is a time of significant hormonal changes, which may contribute to altered body composition and regional adipose tissue accumulation. Excess adiposity, and especially adipose tissue accumulation in the central body region, increases women's risk of cardiovascular and metabolic conditions and affects physical functioning. We investigated the associations between menopausal progression and total and regional body adiposity measured with dual-energy X-ray absorptiometry and computed tomography in two longitudinal cohort studies of women aged 47–55 (n = 230 and 148, mean follow-up times 1.3 ± 0.7 and 3.9 ± 0.2 years, mean baseline BMI 25.5 kg/m2). We also examin…

Design and protocol of Estrogenic Regulation of Muscle Apoptosis (ERMA) study with 47 to 55-year-old women's cohort : novel results show menopause-related differences in blood count

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Perimenopausal women show modulation of excitatory and inhibitory neuromuscular mechanisms.

Background Menopausal transition exposes women to an early decline in muscle force and motor function. Changes in muscle quality and function, especially in lower limbs, are crucial, as they expose individuals to increased risk of falls. To elucidate some of the related neuromuscular mechanisms, we investigated cortical inhibition and peripheral muscle twitch force potentiation in women during the early and late stages of perimenopause. Methods Participants were 63 women aged 48–55 years categorized as early (EP, n = 25) or late (LP, n = 38) perimenopausal according to serum follicle-stimulating hormone (FSH) levels and menstrual diaries. EP women had an irregular menstrual cycle and FSH  2…

Connective tissue of “fast” and “slow” skeletal muscle in rats…effects of endurance training

The connective tissue of two skeletal muscles having different contractile properties was investigated in trained and untrained rats. The animals to be trained were put to run on a treadmill 5 days a week for 4 weeks. The "slow" m. soleus (MS) showed higher malate dehydrogenase activity but lower lactate dehydrogenase activity compared to the "fast" m. rectus femoris (MRF). When whole muscles were taken into account, the concentrations of both hydroxyproline and hexosamines were higher for MS compared to MRF. In the middle section of MS there were more hexosamines than in that of MRF, but no similar difference existed in hydroxyproline. The histochemical staining of collagen, however, sugge…

Leukocyte and Skeletal Muscle Telomere Length and Body Composition in Monozygotic Twin Pairs Discordant for Long-term Hormone Replacement Therapy

Estrogen-based hormone replacement therapy (HRT) may be associated with deceleration of cellular aging. We investigated whether long-term HRT has effects on leukocyte (LTL) or mean and minimum skeletal muscle telomere length (SMTL) in a design that controls for genotype and childhood environment. Associations between telomeres, body composition, and physical performance were also examined. Eleven monozygotic twin pairs (age 57.6 ± 1.8 years) discordant for HRT were studied. Mean duration of HRT use was 7.3 ± 3.7 years in the user sister, while their co-twins had never used HRT. LTL was measured by qPCR and SMTLs by southern blot. Body and muscle composition were estimated by bioimpedance an…

Design and protocol of Estrogenic Regulation of Muscle Apoptosis (ERMA) study with 47 to 55-year-old women's cohort : novel results show menopause-related differences in blood count

Objective: The multidisciplinary Estrogenic Regulation of Muscle Apoptosis (ERMA) study was designed to reveal how hormonal differences over the menopausal stages affect the physiological and psychological functioning of middle-aged women. This paper describes the protocol and nonrespondent analysis of ERMA and novel findings on menopausal differences in blood count variables and their association with female sex hormones. Methods: Women aged 47 to 55 years were assigned to pre, early peri, late peri, and postmenopausal groups based on follicle-stimulating hormone (FSH) and bleeding diary. Multivariate linear regression models were constructed to estimate the association of 17b-estradiol (E…

Endogenous Hormones, Muscle Strength, and Risk of Fall-Related Fractures in Older Women

Background. Among older people, fracture-causing fall often leads to health deterioration. The role of endogenous hormone status and muscle strength on fall-related fracture risk is unclear. This study investigates if, after adjustment for bone density, endogenous hormones and muscle strength would predict fall-related limb fracture incidence in older community-dwelling women followed-up over 10 years. Methods. As a part of a prospective population-based study, 187 75-year-old women were investigated. Serum estradiol, testosterone, sex hormone binding globulin, and dehydroepiandrosterone sulfate concentrations were analyzed, and isometric muscle strength and bone mineral density were assess…

Differences in muscle and adipose tissue gene expression and cardio-metabolic risk factors in the members of physical activity discordant twin pairs

High physical activity/aerobic fitness predicts low morbidity and mortality. Our aim was to identify the most up-regulated gene sets related to long-term physical activity vs. inactivity in skeletal muscle and adipose tissues and to obtain further information about their link with cardio-metabolic risk factors. We studied ten same-sex twin pairs (age range 50-74 years) who had been discordant for leisure-time physical activity for 30 years. The examinations included biopsies from m. vastus lateralis and abdominal subcutaneous adipose tissue. RNA was analyzed with the genome-wide Illumina Human WG-6 v3.0 Expression BeadChip. For pathway analysis we used Gene Set Enrichment Analysis utilizing…

Role of Menopausal Transition and Physical Activity in Loss of Lean and Muscle Mass : A Follow-Up Study in Middle-Aged Finnish Women

In midlife, women experience hormonal changes due to menopausal transition. A decrease especially in estradiol has been hypothesized to cause loss of muscle mass. This study investigated the effect of menopausal transition on changes in lean and muscle mass, from the total body to the muscle fiber level, among 47–55-year-old women. Data were used from the Estrogenic Regulation of Muscle Apoptosis (ERMA) study, where 234 women were followed from perimenopause to early postmenopause. Hormone levels (estradiol and follicle stimulating hormone), total and regional body composition (dual-energy X-ray absorptiometry (DXA) and computed tomography (CT) scans), physical activity level (self-reported…

Blood and skeletal muscle ageing determined by epigenetic clocks and their associations with physical activity and functioning

AbstractThe aim of this study was to investigate the correspondence of different biological ageing estimates (i.e. epigenetic age) in blood and muscle tissue and their associations with physical activity (PA), physical function and body composition. Two independent cohorts (N = 139 and N = 47) were included, whose age span covered adulthood (23–69 years). Whole blood and m. vastus lateralis samples were collected, and DNA methylation was analysed. Four different DNA methylation age (DNAmAge) estimates were calculated using genome-wide methylation data and publicly available online tools. A novel muscle-specific methylation age was estimated using the R-package ‘MEAT’. PA was measured with q…

Hormone replacement therapy enhances IGF-1 signaling in skeletal muscle by diminishing miR-182 and miR-233 expressions: A study on postmenopausal monozygotic twin pairs

MiRNAs are fine-tuning modifiers of skeletal muscle regulation, but knowledge of their hormonal control is lacking. We used a co-twin case–control study design, that is, monozygotic postmenopausal twin pairs discordant for estrogen-based hormone replacement therapy (HRT) to explore estrogen-dependent skeletal muscle regulation via miRNAs. MiRNA profiles were determined from vastus lateralis muscle of nine healthy 54–62- years-old monozygotic female twin pairs discordant for HRT (median 7 years). MCF-7 cells, human myoblast cultures and mouse muscle experiments were used to confirm estrogen’s causal role on the expression of specific miRNAs, their target mRNAs and proteins and finally the ac…