0000000000236791
AUTHOR
Paula H. A. Ronkainen
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…
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…
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…
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…
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…
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,…
Muscle function in monozygotic female twin pairs discordant for hormone replacement therapy
Introduction: Postmenopausal monozygotic twin pairs discordant for hormone replacement therapy (HRT) provide an advantageous study design controlling for genetic background for elucidating the relationships between aging, sex hormone levels, muscle strength, contractile capacity, and fatigability. Methods: Thirteen postmenopausal monozygotic twin pairs discordant for HRT were measured for maximal voluntary torque (MVC) and twitch characteristics using electrical stimulation before and after intermittent dynamic plantarflexor exercise until exhaustion. Results: Peak twitch torque was 32% higher in HRT users than in their non-HRT, genetically identical sisters (P = 0.002), but MVC did not dif…
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…
Baculovirus-mediated immediate-early gene expression and nuclear reorganization in human cells
Baculovirus, Autographa californica multiple nucleopolyhedrovirus (AcMNPV), has the ability to transduce mammalian cell lines without replication. The general objective of this study was to detect the transcription and expression of viral immediate-early genes in human cells and to examine the interactions between viral components and subnuclear structures. Viral capsids were seen in large, discrete foci in nuclei of both dividing and non-dividing human cells. Concurrently, the transcription of viral immediate-early transregulator genes (ie-1, ie-2) and translation of IE-2 protein were detected. Quantitative microscopy imaging and analysis showed that virus transduction altered the size of …