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Purpose Exercise and aging may modulate muscle protein homeostasis and autophagy, but few studies examine highly-trained middle-aged or older individuals. This study elucidated the effects of a new long-term training stimulus on markers of muscle autophagy and unfolded protein response (UPR) and on sprint running performance in masters sprinters. Methods Thirty-two male competitive sprinters (aged 40–76 years) were randomly divided into experimental (EX) and control (CTRL) groups. The EX training program was a combination of heavy and explosive strength and sprint exercises aimed at improving sprint performance. Fifteen and thirteen participants completed the 20-week intervention period in EX and CTRL, respectively. The latter were told to continue their routine exercises. Key protein markers were analyzed by western blotting from vastus lateralis (VL) muscle biopsies. Muscle thickness of VL was analyzed by ultrasonography and sprint performance by a 60-meter running test. Results EX induced improvement in 60-meter sprint performance when compared to controls (time x group, P = 0.003) without changes in VL muscle thickness. Content of lipidated microtubule-associated protein 1A/1B-light chain 3 (LC3-II) increased in EX (P = 0.022) suggesting increased autophagosome content. Additionally, an autophagosome clearance marker sequestosome 1 (p62) decreased in EX (P = 0.006). Markers of UPR selectively modulated with decreases (e.g. ATF4, P = 0.003) and increases (e.g. EIF2α, P = 0.019) observed in EX. Conclusions These findings suggest that a new intensive training stimulus that combines strength training with sprint training may increase muscle autophagosome content in a basal state without any evidence of impaired autophagosome clearance in masters sprinters. Simultaneously, the combined training may have a selective effect on the content of UPR signaling components. peerReviewed

The age-related decline in muscle function, particularly muscle power, is associated with increased risk of important clinical outcomes. Physical activity is an important determinant of muscle function, and different types of physical activity e.g. power-based versus endurance-based exercise appear to have differential effects on muscle power. Cross-sectional studies suggest that participation in power-based exercise is associated with greater muscle power across adulthood but this has not been investigated longitudinally. We recruited eighty-nine male and female power and endurance master athletes (sprint and distance runners respectively, baseline age 35–90y). Using jumping mechanography, we measured lower limb muscle function during a vertical jump including at least two testing sessions longitudinally over 4.5 ± 2.4y. We examined effects of time, discipline (power/endurance) and sex in addition to two- and three-way interactions using linear mixed-effects models. Peak relative power, relative force and jump height, but not Esslingen Fitness Index (indicating peak power relative to sex and age-matched reference data) declined with time. Peak power, force, height and EFI were greater in power than endurance athletes. There were no sex, discipline or sex*discipline interactions with time for any variable, suggesting that changes were similar over time for athletes of both sexes and disciplines. Advantages in lower limb muscle function in power athletes were maintained with time, in line with previous cross-sectional studies. These results suggest that improvements in lower limb function in less active older individuals following power-based training persist with continued adherence, although this requires further investigation in interventional studies. Supplementary Information The online version contains supplementary material available at 10.1007/s00223-021-00907-3.

The ageing-related loss of muscle mass is thought to be partly attributable to motor neuron loss and motor unit remodelling that result in fibre type grouping. We examined fibre type grouping in 19- to 85-year-old athletes and non-athletes and evaluated to which extent any observed grouping is explained by the fibre type composition of the muscle. Since regular physical activity may stimulate reinnervation, we hypothesised that fibre groups are larger in master athletes than in age-matched non-athletes. Fibre type grouping was assessed in m. vastus lateralis biopsies from 22 young (19-27 years) and 35 healthy older (66-82 years) non-athletes, and 14 young (20-29 years), 51 middle-aged (38%65 years) and 31 older (66-85 years) athletes. An "enclosed fibre" was any muscle fibre of a particular type surrounded by fibres of the same type only. A fibre type group was defined as a group of fibres with at least one enclosed fibre. Only type II fibre cross-sectional area (FCSA) showed an age-related decline that was greater in athletes (p < 0.001) than in non-athletes (p = 0.012). There was no significant age-related effect on fibre group size or fibre group number in athletes or non-athletes, and the observed grouping was similar to that expected from the fibre type composition. At face value these observations do 1) neither show evidence for an age-related loss and remodelling of motor units nor 2) improved reinnervation with regular physical activity, but 3) histological examination may not reveal the full extent of ageing-related motor unit remodelling.

Summary We investigated longitudinal changes in tibia bone strength in master power (jumping and sprinting) and endurance (distance) athletes of both sexes. Bone mass but not cross-sectional moment of inertia was better maintained in power than endurance athletes over time, particularly in men and independent of changes in performance. Objective Assessment of effects of sex and athletic discipline (lower limb power events, e.g. sprint running and jumping versus endurance running events) on longitudinal changes in bone strength in masters athletes. Methods We examined tibia and fibula bone properties at distal (4% distal-proximal tibia length) and proximal (66% length) sites using peripheral quantitative computed tomography (pQCT) in seventy-one track and field masters athletes (30 male, 41 female, age at baseline 57.0 ± 12.2 years) in a longitudinal cohort study that included at least two testing sessions over a mean period of 4.2 ± 3.1 years. Effects of time, as well as time × sex and time × discipline interactions on bone parameters and calf muscle cross-sectional area (CSA), were examined. Results Effects of time were sex and discipline-dependent, even following adjustment for enrolment age, sex and changes in muscle CSA and athletic performance. Male sex and participation in power events was associated with better maintenance of tibia bone mineral content (BMC, an indicator of bone compressive strength) at 4% and 66% sites. In contrast, there was no strong evidence of sex or discipline effects on cross-sectional moment of inertia (CSMI, an indicator of bone bending and torsional strength—P > 0.3 for interactions). Similar sex and discipline-specific changes were also observed in the fibula. Conclusions Results suggest that male athletes and those participating in lower limb power-based rather than endurance-based disciplines have better maintenance of bone compressive but not bending and torsional strength.

Exercise and aging may modulate muscle protein homeostasis and autophagy, but few studies examine highly trained middle-age or older individuals. This study elucidated the effects of a new long-term training stimulus on markers of muscle autophagy and unfolded protein response (UPR) and on sprint running performance in masters sprinters.Thirty-two male competitive sprinters (age 40-76 yr) were randomly divided into experimental (EX) and control (CTRL) groups. The EX training program was a combination of heavy and explosive strength and sprint exercises aimed at improving sprint performance. Fifteen and thirteen participants completed the 20-wk intervention period in EX and CTRL, respectively. The latter were told to continue their routine exercises. Key protein markers were analyzed by Western blotting from vastus lateralis (VL) muscle biopsies. The muscle thickness of VL was analyzed by ultrasonography and sprint performance by a 60-m running test.EX induced improvement in 60-m sprint performance when compared with controls (time-group, P = 0.003) without changes in VL muscle thickness. Content of lipidated microtubule-associated protein 1A/1B-light chain 3 (LC3-II) increased in EX (P = 0.022), suggesting increased autophagosome content. In addition, an autophagosome clearance marker sequestosome 1 (p62) decreased in EX (P = 0.006). Markers of UPR selectively modulated with decreases (e.g., ATF4, P = 0.003) and increases (e.g., EIF2α, P = 0.019) observed in EX.These findings suggest that a new intensive training stimulus that combines strength training with sprint training may increase muscle autophagosome content in a basal state without any evidence of impaired autophagosome clearance in masters sprinters. Simultaneously, the combined training may have a selective effect on the content of UPR signaling components.

Age-related reduction in muscle force generation capacity is similarly evident across different lower limb muscle groups, yet decline in locomotor performance with age has been shown to depend primarily on reduced ankle extensor muscle function. To better understand why ageing has the largest detrimental effect on ankle joint function during locomotion, we examined maximal ankle and knee extensor force development during a two-leg hopping test in older and young men, and used these forces as a reference to calculate relative operating efforts for the knee and ankle extensors as participants walked, ran and sprinted. We found that, across locomotion modes in both age groups, ankle extensors operated at a greater relative effort compared to knee extensors; however, slightly less pronounced differences between ankle and knee extensor muscle efforts were present among older men, mainly due to a reduction in the ankle extensor force generation during locomotion modes. We consider these findings as evidence that reduced ankle push-off function in older age is driven by a tendency to keep ankle extensor effort during locomotion lower than it would otherwise be, which, in turn, may be an important self-optimisation strategy to prevent locomotor-induced fatigue of ankle extensor muscles.

Diet composition influences acid-base status of the body. This may become more relevant as renal functional capacity declines with aging. We examined the effects of low (LD) versus high dietary acid load (HD) on blood acid-base status and exercise performance. Participants included 22 adolescents, 33 young adults (YA), and 33 elderly (EL), who followed a 7-day LD and HD in a randomized order. At the end of both diet periods the subjects performed a cycle ergometer test (3 × 10 min at 35%, 55%, 75%, and (except EL) until exhaustion at 100% of maximal oxygen uptake). At the beginning of and after the diet periods, blood samples were collected at rest and after all workloads. Oxygen uptake, respiratory exchange ratio (RER), and heart rate (HR) were monitored during cycling. In YA and EL, bicarbonate (HCO3−) and base excess (BE) decreased over the HD period, and HCO3−, BE, and pH were lower at rest after HD compared with LD. In YA and EL women, HCO3− and BE were lower at submaximal workloads after HD compared with LD. In YA women, the maximal workload was 19% shorter and maximal oxygen uptake, RER, and HR were lower after HD compared with LD. Our data uniquely suggests that better renal function is associated with higher availability of bases, which may diminish exercise-induced acidosis and improve maximal aerobic performance. Differences in glomerular filtration rate between the subject groups likely explains the larger effects of dietary acid load in the elderly compared with younger subjects and in women compared with men.

According to cross-sectional and interventional studies, high-intensity strength and impact-type training provide a powerful osteogenic stimulus even in old age. Longitudinal evidence on the ability of high-intensity training to attenuate age-related bone deterioration is currently lacking, however. This follow-up study assessed the role of continued strength and sprint training on bone aging in 40- to 85-year-old male sprinters (n=69) with long-term training background. pQCT-derived bone structural, strength and densitometric parameters of the distal tibia (5% distal-proximal tibia length) and tibial midshaft (50% length) were assessed at baseline and after 10 years. The groups of well-trained (actively competing, sprint training including strength training >=2 times/wk; n=36) and less-trained (

This study investigated the whole body frontal plane mechanics among young (26 ± 6 years), early old (61 ± 5 years), and old (78 ± 4 years) adults during walking, running, and sprinting. The age-groups had similar walking (1.6 m/s) and running (4.0 m/s) speeds, but different maximal sprinting speed (young 9.3 m/s, early old 7.9 m/s, and old 6.6 m/s). Surprisingly, although the old group exerted much lower vertical ground reaction force during running and sprinting, the hip frontal plane moment did not differ between the age-groups. Kinematic analysis demonstrated increased hip adduction and pelvis drop, as well as reduced trunk lateral flexion among old adults, especially during sprinting. These alterations in the hip and pelvis motions may reflect insufficient force production of hip abductors to stabilize the pelvis during single-limb support, while limited trunk lateral flexion may enhance control of the mediolateral balance. On the other hand, larger trunk side-to-side movement among the young and early old adults may provide a mechanism to prevent the increase of the hip frontal moment despite greater vertical ground reaction force. This, in turn, can assist hip abductors to maintain stability of the pelvis during sprinting while allowing powerful force generation by a large adductor muscle group.

Diets rich in animal protein and cereal grains and deficient in vegetables and fruits may cause low-grade metabolic acidosis, which may impact exercise and health. We hypothesized that (1) a normal-protein diet with high amount of vegetables and fruits (HV) induces more alkaline acid-base balance compared with a high-protein diet with no vegetables and fruits (HP) and (2) diet composition has a greater impact on acid-base balance in the elderly (ELD).In all, 12-15 (adolescents (ADO)), 25-35 (young adults (YAD)) and 60-75 (ELD)-year-old male and female subjects (n=88) followed a 7-day HV and a 7-day HP in a randomized order and at the end performed incremental cycle ergometer tests. We investigated the effect of diet composition and age on capillary (c-pH) and urine pH (u-pH), strong ion difference (SID), partial pressure of carbon dioxide (pCO2) and total concentration of weak acids (Atot). Linear regression analysis was used to examine the contribution of SID, pCO2 and Atot to c-pH.In YAD and ELD, c-pH (P⩽0.038) and u-pH (P0.001) were higher at rest after HV compared with HP. During cycling, c-pH was higher (P⩽0.034) after HV compared with HP at submaximal workloads in YAD and at 75% of VO2max (maximal oxygen consumption) in ELD. The contribution of SID, pCO2 and Atot to c-pH varied widely. Gender effects or changes in acid-base balance of ADO were not detected.A high intake of vegetables and fruits increases blood and u-pH in YAD and ELD. ELD compared with younger persons may be more sensitive for the diet-induced acid-base changes.

This randomized, controlled, high-intensity strength and sprint training trial in middle-aged and older male sprint athletes showed significant improvements in mid-tibial structure and strength. The study reveals the adaptability of aging bone, suggesting that through a novel, intensive training stimulus it is possible to strengthen bones during aging. High-load, high-speed and impact-type exercise may be an efficient way of improving bone strength even in old age. We evaluated the effects of combined strength and sprint training on indices of bone health in competitive masters athletes, who serve as a group of older people who are likely to be able to participate in vigorous exercise of this kind. Seventy-two men (age 40–85) were randomized into an experimental (EX, n = 40) and a control (CTRL, n = 32) group. EX participated in a 20-week program combining heavy and explosive strength exercises with sprint training. CTRL maintained their usual, run-based sprint training schedules. Bone structural, strength and densitometric parameters were assessed by peripheral QCT at the distal tibia and tibial midshaft. The intervention had no effects on distal tibia bone traits. At the mid-tibia, the mean difference in the change in cortical thickness (ThCO) in EX compared to CTRL was 2.0% (p = 0.007). The changes in structure and strength were more pronounced in the most compliant athletes (training adherence >75%). Compared to CTRL, total and cortical cross-sectional area, ThCO, and the area and density-weighted moments of inertia for the direction of the smallest flexural rigidity (I minA , I minD ) increased in EX by 1.6–3.2% (p = 0.023–0.006). Polar mass distribution analysis revealed increased BMC at the anteromedial site, whereas vBMD decreased (p = 0.035–0.043). Intensive strength and sprint training improves mid-tibia structure and strength in middle-aged and older male sprint athletes, suggesting that in the presence of high-intensity loading exercise, the adaptability of the bone structure is maintained during aging.

The knee and ankle extensors as human primary antigravity muscle groups are of utmost importance in a wide range of locomotor activities. Yet, we know surprisingly little about how these muscle groups work, and specifically, how close to their maximal capacities they function across different modes and intensity of locomotion. Therefore, to advance our understanding of locomotor constraints, we determined and compared relative operating efforts of the knee and ankle extensors during walking, running, and sprinting.Using an inverse dynamics biomechanical analysis, the muscle forces of the knee and ankle extensors during walking (1.6 m·s), running (4.1 m·s), and sprinting (9.3 m·s) were quantified and then related to maximum forces of the same muscle groups obtained from a reference hopping test that permitted natural elastic limb behavior.During walking, the relative effort of the ankle extensors was almost two times greater compared with the knee extensors (35% ± 6% vs 19% ± 5%, P0.001). Changing walking to running decreased the difference in the relative effort between the extensor muscle groups, but still, the ankle extensors operated at a 25% greater level than the knee extensors (84% ± 12% vs 63% ± 17%, P0.05). At top speed sprinting, the ankle extensors reached their maximum operating level, whereas the knee extensors still worked well below their limits, showing a 25% lower relative effort compared with the ankle extensors (96% ± 11% vs 72% ± 19%, P0.01).Regardless of the mode of locomotion, humans operate at a much greater relative effort at the ankle than knee extensor muscles. As a consequence, the great demand on ankle extensors may be a key biomechanical factor limiting our locomotor ability and influencing the way we locomote and adapt to accommodate compromised neuromuscular system function.

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 neutrophils and negative for lymphocytes, red blood cells, HGB, FasL, and miR-146a. During the 10-year follow-up, FasL decreased (P=0.017) and miR-21 (P<0.001) and miR-146a (P=0.005) levels increased. When combining the molecule levels, aging, and physical performance, FasL associated with countermovement jump and bench press (P<0.001), miR-21 and miR-146a with knee flexion (P=0.023;P<0.001), and bench press (P=0.004;P<0.001) and miR-146a with sprint performance (P<0.001). The studied serum molecules changed in an age-dependent manner and were associated with declining physical performance. They have potential as biomarkers of aging-related processes influencing the development of physiological dysfunctions. Further research is needed focusing on the origins and targets of circulating microRNAs to clarify their function in various tissues with aging.

Background: The nature versus nurture debate is one of the oldest issues in the study of longevity, health and successful aging. Objective: We present a 97-year-old man (I.K.) as an example of the effects of habitual exercise on the aging process. Methods: Extensive assessments included medical examinations, interviews, musculoskeletal structure, performance characteristics, cognitive function and gut microbiota composition. Results: I.K. suffers from iatrogenic hypogonadism, prostate cancer, hypothyroidism and a history of deep popliteal thrombosis. Notwithstanding, he cycles up to 5,000 km a year and participates in competitive sports. His musculoskeletal properties, athletic performance, cognitive function and gut microbiota are outstanding. Some traits even exceed those seen in middle-aged men. Conclusions: His long-term physically and intellectually active lifestyles combined with extensive social interactions have most likely contributed to his exercise capacity, despite his medical history.

This study was undertaken to examine bone properties in masters sprinters of different ages and younger reference subjects. In addition, the association of sport-specific ground reaction force, muscle, training, and hormone characteristics with the bone parameters was evaluated in the athletes.Bone densitometric, structural, and strength parameters were assessed by peripheral quantitative computed tomography at the distal and midtibia in 83 male sprinters (40-85 yr) and 19 physically active referents (31-45 yr). Between-group differences were analyzed by ANCOVA with body mass and height as covariates.Bone values were generally greater in athletes than referents, the greatest differences being in bending strength of the tibia shaft as estimated by maximum moment of inertia (Imax). Among athletes, trabecular volumetric bone mineral density of distal tibia was 12% (P0.05) lower in the oldest (≥70 yr) versus youngest group, whereas the total bone mineral content, total cross-sectional area, and compressive bone strength index did not differ between the groups. At midtibia, no age group differences were present in the total bone mineral content, total cross-sectional area, cortical wall thickness, cortical volumetric bone mineral density, polar mass distribution, minimum moment of inertia, or maximum moment of inertia. After controlling for age, body mass, and height, most loading-related characteristics, knee extensor muscle thickness, and hormone concentrations correlated with the bone parameters. Multivariate regression models explained 12%-67% (mean, 47.5%) of the variance of the bone parameters. Mechanical power in the eccentric phase of the hopping and body mass were consistently the strongest independent predictors in the models.The results suggest that regular sprint training has positive (direction-specific) effects on bone strength and structure in middle- and older-aged athletes. Interindividual differences in bone traits seem to be due to combined effects of exercise loading, body size, and hormonal characteristics.

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, HRT users had 9% [95% confidence interval (CI) 3%–15%] higher estimated bending strength than their nonusing cotwins. Larger cortical area and higher cortical bone mineral density accounted for this difference. The cortex was larger in the HRT users in the endocortical region. In the distal tibia, estimated compressive strength was 24% (95% CI 9%–40%) higher and in the distal radius 26% (95% CI 11%–41%) higher in the HRT users than in their nonusing cotwins owing to higher volumetric bone mineral density. No difference between users and nonusers was observed in total bone cross-sectional area in any measured bone site. The added mineral mass in the HRT users was distributed evenly within and between bone sites. In postmenopausal women, long-term HRT preserves estimated bone strength systemically by preventing bone mineral loss similarly in body weight–loaded and non-weight-loaded bone. © 2011 American Society for Bone and Mineral Research.

Elite master athletes with long-term devotion to physical training offer an economical means of investigating the effects of ageing and habitual exercise on maximal physical performance. Ideally, individuals with optimised living habits throughout their lives could serve as a human model of ‘primary’ or ‘inherent’ ageing, where age-related changes are not confounded by sedentary life-style and associated chronic diseases. A limitation of this approach is the selection bias as those with inherently high physical capacity and good health participate in competitive sports. The age-related decrements remain obvious, but the record performances of master athletes competing in running and jumping events are preserved at an extraordinary high level until old age. Similarly, underlying capacities such as muscle strength, power and endurance remain far above the age norms, thus providing superior functional reserves for activities of daily living. Nevertheless, even the best records may overestimate the age decrements. It is obvious that the older champions have never trained and performed as well as the current younger athletes, and that the performance of individual athletes retaining or increasing their training volume and intensity show smaller decrements over the years. The plasticity of individual development is preserved in later life thus making it possible, at least for some time, to modify the age-associated decline in the different aspects of maximal physical performance.

Eighteen young (23 ± 4 yr) and 25 older (70 ± 4 yr) male sprinters were examined for ground reaction force (GRF) and temporal-spatial variables. The data were collected during maximum-speed phase, and variability and symmetry indices were calculated from a total of 8 steps. There was little variation (CV < 6%) in vertical and resultant GRF and kinematic variables, while impact loading had high variability (CV: 10–21%). Overall, the pattern of variability was similar in both groups. Yet, a small but significant age-related increase in CV was evident in horizontal GRFs. There was a variable-specific asymmetry between legs but it was not related to leg dominance. No age differences existed in the symmetry indices. Results indicate that only selected force platform variables are symmetric and repeatable enough so that their use for comparison purposes is appropriate. Data also suggest that aging may increase variability in certain biomechanical measures, whereas symmetry is not affected by age.

Both physical activity and body mass affect bone properties. In this study we examined how diet-induced obesity combined with voluntary physical activity affects bone properties. Forty 7-week-old male C57BL/6J mice were assigned to four groups evenly: control diet (C), control diet + running (CR), high-fat diet (HF, 60% energy from fat), and high-fat diet + running (HFR). After 21-week intervention, all mice were killed and the left femur was dissected for pQCT and mechanical measurements. Body mass increased 80% in HF and 62% in HFR, with increased epididymal fat pad weight and impaired insulin sensitivity. Except for total and trabecular volumetric bone mineral density (BMD), bone traits correlated positively with body mass, fat pad, leptin, and osteoprotegerin. Obesity induced by a high-fat diet resulted in increased femoral bone cross-sectional area, mineral content (BMC), polar moment of inertia, and mechanical parameters. Of the mice accessing the running wheel, those fed the control diet had thinner cortex and less total metaphyseal BMC and BMD, with enlarged metaphyseal marrow cavity, whereas mice fed the high-fat diet had significantly higher trabecular BMD and smaller marrow cavity. However, the runners had a weaker femoral neck as indicated by decreased maximum flexure load. These results suggest that voluntary running exercise affects bone properties in a site-specific manner and that there is a complex interaction between physical activity and obesity. Thus, both diet and exercise should be considered when optimizing the effects on body composition and bone, even though the underlying mechanisms remain partly unknown.

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 differentially expressed genes. The hierarchical clustering method was used to assort the genes. Additionally, enrichment analysis of gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was carried out to clarify whether assorted gene clusters are enriched with particular functional categories. The analysis revealed transcriptional regulation of 49 GO/KEGG categories. PT upregulated transcription in “response to contraction”—category revealing novel candidate genes for contraction-related regulation of muscle function while HRT upregulated gene expression related to functionality of mitochondria. Moreover, several functional categories tightly related to muscle energy metabolism, development, and function were affected regardless of the treatment. Our results emphasize that during the early stages of the postmenopause, muscle properties are under transcriptional modulation, which both PT and HRT partially counteract leading to preservation of muscle power and potentially reducing the risk for aging-related muscle weakness. More specifically, PT and HRT may function through improving energy metabolism, response to contraction as well as by preserving functionality of the mitochondria. Electronic supplementary material The online version of this article (doi:10.1007/s11357-010-9140-1) contains supplementary material, which is available to authorized users.

The structural and geometrical properties of the tibia shaft were investigated at two sections by means of computerized tomography (CT) in 78-year-old women with high (n = 19) and low (n = 17) calcaneal bone mineral density (BMD, g/cm3) previously measured by 125I-photon absorption. The high BMD group had a 20-21% higher tibial BMD and 9-12% higher bone cross-sectional area than was observed in the low BMD group. The distribution of bone mass indicated that the low BMD group had lost bone mainly from the endosteal surface, especially in the anterior part of the tibia. However, both groups had a similar basic pattern of mass distribution at the measured sections. The high BMD group had higher moments of inertia at the upper section than the low BMD group. The differences between the groups were more pronounced when only the high density areas were included. At the lower section, the differences between the groups also appeared significant at the high density levels. There were no group differences in the area moments of inertia. The results suggest that the true distribution of bone mass should be taken into account in determining the moments of inertia. In the tibia, determination of the cross-sectional mass distribution of bone combined with BMD should have a better discriminatory capability than BMD only in studying bone strength and fracture risk.

The purpose of this 7-year prospective longitudinal study was to examine whether the level and consistency of leisure-time physical activity (LTPA) during adolescence affected the bone mineral content (BMC) and bone mineral density (BMD) attained at early adulthood. The study subjects were 202 Finnish girls who were 10 to 13 years of age at baseline. Bone area (BA), BMC, and BMD of the total body (TB), total femur (TF), and lumbar spine (L2–L4) were assessed by dual-energy X-ray absorptiometry (DXA). Scores of LTPA were obtained by questionnaire. Girls were divided into four groups: consistently low physical activity (GLL), consistently high (GHH), and changed from low to high (GLH) and from high to low (GHL) during 7 years of follow-up. At baseline, no differences were found in BA, BMC, and BMD among the groups in any of the bone sites. Compared with the GLL group, the GHH group had higher BMC (11.7% in the TF, p

The aetiology of increased incidence of fracture during puberty is unclear. This study aimed to determine whether low volumetric bone mineral density (vBMD) in the distal radius is associated with upper-limb fractures in growing girls, and whether any such vBMD deficit persists into adulthood. Fracture history from birth to 20 years was obtained and verified by medical records in 1034 Finnish girls aged 10–13 years. Bone density and geometry at distal radius, biomarkers and lifestyle/behavioural factors were assessed in a subset of 396 girls with a 7.5-year follow-up. We found that fracture incidence peaked during puberty (relative risk 3.1 at age of 8–14 years compared to outside this age window), and 38% of fractures were in the upper-limb. Compared to the non-fracture cohort, girls who sustained upper-limb fracture at ages 8–14 years had lower distal radial vBMD at baseline (258.9 ± 37.5 vs. 287.5 ± 34.1 mg/cm 3 , p = 0.001), 1-year (252.0 ± 29.3 vs. 282.6 ± 33.5 mg/cm 3 , p = 0.001), 2-year (258.9 ± 32.2 vs. 289.9 ± 40.1 mg/cm 3 , p = 0.003), and 7-year follow-ups (early adulthood, 307.6 ± 35.9 vs. 343.6 ± 40.9 mg/cm 3 , p = 0.002). There was a consistent trend towards larger bone cross-sectional area in the fracture cohort compared to non-fracture. In a logistic regression model, lower vBMD ( p = 0.001) was the only significant predictor of upper-limb fracture during the period of 8–14 years. Our results indicate that low BMD is an important factor underlying elevated upper-limb fracture risk during puberty, and that low BMD in pubertal girls with fracture persists into adulthood. Hence low vBMD during childhood is not a transient deficit. Methods to monitor vBMD and to maximise bone mineral accrual and reduce risks of falling in childhood should be developed.

to the editor: Interpretations on the effect of estrogen/sex should be based on direct measures of muscle injury and subsequent repair/regeneration (i.e., improvements in muscle structure and function after injurious exercise). The inclusion of indexes of the inflammatory response (e.g.

The purpose of this study was to estimate to what extent muscle cross-sectional area of the lower leg (mCSA) and tibial structural strength are influenced by common and trait-specific genetic and environmental factors. pQCT scans were obtained from both members of 102 monozygotic (MZ) and 113 dizygotic (DZ) 63- to 76-yr-old female twin pairs to estimate the mCSA of the lower leg, structural bending strength of the tibial shaft (BSIbend), and compressive strength of the distal tibia (BSIcomp). Quantitative genetic models were used to decompose the phenotypic variances into common and trait-specific additive genetic (A), shared environmental (C), and individual environmental (E) effects. The age-adjusted trivariate independent pathway model showed that the total relative contributions of A, C, and E were, respectively, 75%, 0%, and 25% for mCSA, 55%, 20%, and 25% for BSIbend, and 40%, 37%, and 23% for BSIcomp. In addition, the model showed that all three traits shared genetic and individual environmental factors. BSIbend and BSIcomp had common shared environmental factors and were also influenced by trait-specific genetic factors. In conclusion, the association between muscle cross-sectional area and structural bone strength has its origins in both genetic and environmental effects in older women. These results suggest that in older women the same genetic and environmental factors may predispose to or, conversely, protect from both sarcopenia and bone fragility.

The aims of this study were to investigate the mechanisms underlying (1) the ageing-related motor handicap at the whole muscle, cellular, contractile protein and myonuclear levels; and (2) ageing-related differences in muscle adaptability.In vivo muscles function was studied in the knee extensors. Decreases were observed in isokinetic and isometric torque outputs in old age in the sedentary men and women and elite master sprinters. A 20-week long specific sprint and resistance training successfully improved the maximal isometric force and rate of force development in a subgroup of master sprinters.In vitro measurements were performed in muscle biopsies from the vastus lateralis muscle. Immunocytochemical and contractile measurements in single membrane permeabilized muscle fibres demonstrated ageing- and gender-related changes at the myofibrillar level. In sedentary subjects, data showed a preferential decrease in the size of muscle fibres expressing type IIa MyHC in men, lower force generating capacity in muscle fibres expressing the type I MyHC isoform in both men and women and lower maximum velocity of unloaded shortening (V0) in fibres expressing types I and IIa MyHC isoforms in both men and women. The master sprinters also experienced the typical ageing-related reduction in the size of fast-twitch fibres, a shift toward a slower MyHC isoform profile and a lower V0 of type I MyHC fibres, which played a role in the decline in explosive force production capacity. The fast-twitch fibre area increased after the resistance training period. A model combining single muscle fibre confocal microscopy with a novel algorithm for 3D imaging of myonuclei in single muscle fibre segments was introduced to study the spatial organisation of myonuclei and the size of individual myonuclear domains (MNDs). Significant changes in the MND size variability and myonuclear organization were observed in old age, irrespective gender and fibre type. Those changes may influence the local quantity of specific proteins per muscle fibre volume by decreased and/or local cooperativity of myonuclei in a gender and muscle fibre specific manner.In conclusion, the ageing-related impairments in in vivo muscle function were related to significant changes in morphology, contractile protein expression and regulation at the muscle fibre level. It is suggested that the altered myonuclear organisation observed in old age impacts on muscle fibre protein synthesis and degradation with consequences for the ageing-related changes in skeletal muscle structure and function. However, the improved muscle function in response to a 20-week intense physical training regime in highly motivated physically active old subjects demonstrates that all ageing-related in muscle function are not immutable.

A bivariate genetic analysis among 217 older female twin pairs showed that, although the structural strength of tibia and radius are mainly regulated by same genetic and environmental factors, the tibia is more affected by environment. Introduction: The habitual loading environment of the bone may modulate the relative contribution of genetic and environmental factors to bone structure. The purpose of this study was to estimate the contribution of the common and site-specific genetic and environmental factors to interindividual variation in compressive structural strength of the weight-bearing tibia and non–weight-bearing radius. Materials and Methods: pQCT scans were obtained from both members of 103 monozygotic (MZ) and 114 dizygotic (DZ) 63- to 76-yr-old female twin pairs to estimate the compressive strength of the distal tibia and distal radius. Quantitative genetic models were used to decompose the phenotypic variance into additive genetic, shared environmental, and individual environmental effects at each bone site and to study whether these bone sites share genetic or environmental effects. Results: The MZ and DZ twins did not differ in mean age, height, weight, or bone structural strength. The age-adjusted Cholesky model showed that additive genetic factors accounted for 83% (95% CI, 77–88%) of the variance in radial strength and 61% (95% CI, 52–69%) of the variance in tibial strength, and these were fully correlated. A shared environmental factor accounted for 15% (95% CI, 10–20%) of tibial strength. An individual environmental factor accounted for 17% (95% CI, 12–23%) of the variance in radial strength and 10% (95% CI, 5–17%) of the variance in tibial strength. The relative contribution of an individual environmental factor specific to tibial strength was 14% (95% CI, 11–18%). Conclusions: The results suggest that, in older women, the majority of the individual differences in the compressive structural strength of the forearm and leg are regulated by genetic and environmental factors that are common to both bone sites. However, the relative importance of environmental factors was greater for the weight-bearing tibia than for the non–weight-bearing radius. Thus, the heritability of bone strength seems to vary between skeletal sites according to differences in the typical loading environment.

Isometric maximal strength of hand grip, elbow flexion, knee extension, trunk extension and trunk flexion was studied in representative samples of 75-year-old residents of 3 Nordic localities: Glostrup in Denmark, Gothenburg in Sweden and Jyvaskyla in Finland. The study forms a part of a wider comparative research project analyzing the functional capacity and health of 75-year-olds in these towns. The strength measurements were carried out using standardized techniques and identical dynamometers. The results showed that the strength values of the limb muscles were significantly lower among the 75-year-olds in Jyvaskyla, both in absolute values and in relative units (N/kg body mass). For the trunk muscles, the women in Glostrup had significantly lower strength values than their counterparts from the two other localities, while among men there were no significant differences. The isometric strength values correlated strongly with the anthropometric characteristics, especially lean body mass. This was true for all the muscle groups studied. The results thus indicated considerable differences in muscular strength between the 75-year-olds in the 3 Nordic localities. These differences may partly be due to differences in basic anthropometric characteristics.

Sarcopenia and osteoporosis, the complications of the age-related deterioration of the musculoskeletal system, result in increased risk of fracture, disability and death in old age. Consequently, the structure and function of skeletal muscle and bone and their adaptability are essential aspects of overall health, functional capacity and mobility during the whole lifespan. There is convincing clinical evidence that progressive resistance exercise training improves the properties of skeletal muscle in men and women across the age spectrum, thus providing a high reserve capacity for coping with the functional demands of physical tasks. Regarding bones, exercise is most effective during growth, the average gain in bone mineral content (BMC) and density (BMD) in controlled trials being of the order of 2–5% per year. The net gain of BMD after exercise interventions among older people is modest at a level of 1–3% per year. The functional structure of bone may also change as a result of training and other treatme...

Biopsy samples were taken from the vastus lateralis of 18- to 84-yr-old male sprinters ( n = 91). Fiber-type distribution, cross-sectional area, and myosin heavy chain (MHC) isoform content were identified using ATPase histochemistry and SDS-PAGE. Specific tension and maximum shortening velocity ( Vo) were determined in 144 single skinned fibers from younger (18–33 yr, n = 8) and older (53–77 yr, n = 9) runners. Force-time characteristics of the knee extensors were determined by using isometric contraction. The cross-sectional area of type I fibers was unchanged with age, whereas that of type II fibers was reduced ( P < 0.001). With age there was an increased MHC I ( P < 0.01) and reduced MHC IIx isoform content ( P < 0.05) but no differences in MHC IIa. Specific tension of type I and IIa MHC fibers did not differ between younger and older subjects. Vo of fibers expressing type I MHC was lower ( P < 0.05) in older than in younger subjects, but there was no difference in Vo of type IIa MHC fibers. An aging-related decline of maximal isometric force ( P < 0.001) and normalized rate of force development ( P < 0.05) of knee extensors was observed. Normalized rate of force development was positively associated with MHC II ( P < 0.05). The sprint-trained athletes experienced the typical aging-related reduction in the size of fast fibers, a shift toward a slower MHC isoform profile, and a lower Vo of type I MHC fibers, which played a role in the decline in explosive force production. However, the muscle characteristics were preserved at a high level in the oldest runners, underlining the favorable impact of sprint exercise on aging muscle.

The main function of bone is to provide the mechanical integrity for locomotion and protection; accordingly, bone mass and architecture are adjusted to control the strains produced by mechanical load and muscular activity. Age-related patterns involve peak bone mass during growth, a plateau in adulthood, and bone loss during aging. The decline in bone mass and structural integrity results in increased risk of fractures, particularly in post-menopausal women. Athletes competing in strength and power events, such as weight-lifting and jumping, have superior bone mass and structure compared with their untrained counterparts in all age groups. Exercise seems to be most effective during rapid growth, the average gain in bone mineral content (BMC) and density (BMD) in controlled trials being of the order of 2–5% per year. The net gain of BMD after exercise interventions among older people is modest, at a level of 1–3% per year, but it is not clear whether positive effects can be maintained over a longer time. Although aerobic exercise is important in maintaining overall health, the resistance type of muscle training may be more applicable to the basic rules of bone adaptation and site-specific effects of exercise, have more favorable effects in maintaining or improving bone mass and architecture, and be safe and feasible for older people. It has been suggested that there is an opportunity for resistance training, for improved effects on BMD in post-menopausal women in bones which have less daily loading. In addition to BMC and BMD, bone geometry and mass distribution may also change as a result of training and other treatment, such as hormonal replacement therapy, thereby further improving bone strength and reducing fracture risk. Appropriate training regimens may reduce the risk of falls and the severity of fall-related injuries, and also constitute potential therapy to improve functional ability and the quality of life in osteoporotic patients. However, further research is needed on dose-response relationships between exercise and bone strength, the feasibility of high-load, high-speed and impact-type of physical training, and the risks and benefits of intensive exercise in elderly individuals.

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 assessed. Fall-related limb fractures were gathered from patient records. Results. Serum estradiol concentration was a significant predictor of fall-related limb fractures. Women with serum estradiol concentrations less than 0.022 nmol/L had a 3-fold risk (relative risk 3.05; 95% confidence interval, 1.26–7.36), and women with estradiol concentrations between 0.022 and 0.066 nmol/L doubled the risk (relative risk 2.24; 95% confidence interval, 0.97–5.19) of fall-related limb fracture compared to the women with estradiol concentrations above 0.066 nmol/L. Adjustment for muscle strength and bone mineral density did not materially change the risk estimates. High muscle strength was associated with a low incidence of fall-related limb fractures. Conclusions. This study showed that in 75-year-old women higher serum estradiol concentration and greater muscle strength were independently associated with a low incidence of fall-related limb fractures even after adjustment for bone density. Our results suggest that hormonal status and muscle strength have their own separate mechanisms protecting from fall-related fractures. This finding is of importance in developing preventive strategies, but calls for further study.

Hormone replacement therapy (HRT) has been reported to exert a positive effect on preserving muscle strength following the menopause, however, the mechanism of action remains unclear. We examined whether the mechanism involved preservation of muscle composition as determined by skeletal muscle attenuation. Eighty women aged 50-57 years were randomly assigned to either: HRT, exercise (Ex), HRT + exercise (ExHRT), and control (Co) for 1 year. The study was double-blinded with subjects receiving oestradiol and norethisterone acetate (Kliogest) or placebo. Exercise included progressive high-impact training for the lower limbs. Skeletal muscle attenuation in Hounsfield units (HU) was determined by computed tomography of the mid-thigh. Areas examined were the quadriceps compartment (includes intermuscular adipose tissue), quadriceps muscles, the posterior compartment and posterior muscles. Muscle performance was determined by knee extensor strength, vertical jump height, and running speed over 20 m. Fifty-one women completed the intervention. Vertical jump height and running speed improved in the HRT and ExHRT groups compared with Co (interaction, P < 0.01). For both the quadriceps compartment and quadriceps muscles, HU significantly increased (interaction, P

This prospective study was aimed at evaluating risk factors for symptomatic stress fractures among 179 Finnish male military recruits, aged 18 to 20 years. The subjects were studied in the very beginning of the military service of 6 to 12 months in summer. Bone mineral content (BMC) and density (BMD) were measured by dual energy X-ray absorptiometry (DXA) at the lumbar spine and at the hip and heel ultrasound investigation was performed. Blood was sampled for determination of serum total and free testosterone, total and free estradiol, sex hormone-binding globulin (SHBG), procollagen type I N propeptide, total and carboxylated osteocalcin, tartrate-resistant acid phosphatase 5b, 25-hydroxyvitamin D (25-OHD), and intact parathyroid hormone (iPTH), as well as for studying the XbaI and PvuII polymorphisms of the estrogen receptor gene and the CAG repeat polymorphism of the androgen receptor gene. Urine was collected for the determination of N-terminal cross-linking telopeptide of type I collagen. Muscle strength was measured and Cooper's test was performed. Current exercise, smoking, calcium intake, and alcohol consumption were recorded using a questionnaire. During military service, 15 men experienced a stress fracture, diagnosed with X-ray in 14 and with nuclear magnetic resonance in one man. Those who experienced a fracture were taller than those who did not (P = 0.047). The result of Cooper's test was worse in the fracture group than in the non-fracture group (P = 0.026). Femoral neck and total hip BMC and BMD, adjusted for age, weight, height, exercise, smoking, and alcohol and calcium intake were lower (P = 0.021-0.041) for the fracture group. Stress fractures associated with higher iPTH levels (P = 0.022) but not with lower 25-OHD levels. Bone turnover markers as well as sex hormone and SHBG levels were similar for men with and without stress fracture. There was no difference in the genetic analyses between the groups. In conclusion, tall height, poor physical conditioning, low hip BMC and BMD, as well as high serum PTH level are risk factors for stress fractures in male Finnish military recruits. Given the poor vitamin D status of young Finnish men, intervention studies of vitamin D supplementation to lower serum PTH levels and to possibly reduce the incidence of stress fractures are warranted.

This study aimed to evaluate the influence of leisure-time physical activity on the development of bone mass and density in early pubertal girls. Scores of physical activity were obtained from 242 Finnish girls (10-12 years old within Tanner Stages I-II) using a questionnaire. Bone mass and density were assessed using different densitometric techniques. At Tanner Stage I, active girls had significantly higher bone mineral mass (BMC) and areal bone mineral density (aBMD) of the whole body and cortical volumetric BMD and thickness of the tibial shaft compared with sedentary girls (P

OBJECTIVES: To investigate the association between muscle size, density, and fiber composition; body composition; maximal isometric knee extension strength (KES); and lower-body muscle power in healthy postmenopausal women. DESIGN: Cross-sectional analysis of baseline data from a 1-year randomized controlled experiment. SETTING: University-based research laboratory. PARTICIPANTS: Seventy-eight healthy postmenopausal women aged 50 to 57. MEASUREMENTS: Maximal lower-body muscle power was assessed using vertical jump height (VJH). Maximal isometric KES was measured on a dynamometer chair. Computed tomography scans were used to determine lean-tissue cross-sectional area and density of the thigh and lower leg muscles. Relative area occupied by type I, IIa, Ilax, and IIx muscle fibers was assessed from the vastus lateralis muscle. Lean body mass and total body fat mass were assessed using bioelectrical impedance. RESULTS: High VJH was associated with low body fat mass, high KES, and high density of thigh and lower leg muscles. Multivariate linear regression modeling revealed that high thigh muscle density (β = 0.242; P = .019), relative area occupied by the fastest muscle fiber types (IIax + IIx; β = 0.246; P = .007), KES (β = 0.247; P = .007), and low body fat mass (β = -0.455; P < .001) were independently associated with high VJH, accounting for 45% of the variability in VJH. CONCLUSION: This study showed that thigh muscle composition, muscle strength, and body fat mass are important determinants of lower-body muscle power production during weight-bearing activity in healthy postmenopausal women.

This study was undertaken to investigate age-related differences in the velocity and selected stride parameters in male and female master sprinters and to determine which stride characteristics were related to the overall decline in the performance of the 100 m with age.The performances of 70 finalists (males 40-88 yr, females 35-87 yr) at the European Veterans Athletics Championships were recorded using two high-speed cameras (200 Hz) with a panning video technique and distance markers at 10-m intervals. Velocity, stride length (SL), stride rate (SR), ground contact time (CT), and flight time (FT) during the acceleration, peak velocity, and deceleration phases of the 100-m race were determined from the video records with the aid of the Peak Performance analysis system.There was a general decline in sprint performances with age, the decrease becoming more evident around 65-70 yr of age. The velocity during the different phases of the run declined on average from 5 to 6% per decade in males and from 5 to 7% per decade in females. Similarly, SL showed clear reductions with increasing age, whereas SR remained unchanged until the oldest age groups in both genders. Furthermore, the CT, which correlated with velocity, was significantly longer, and FT, which correlated with both velocity and SL, was shorter in older age groups.Our findings indicated that age-associated differences in velocity in elite master sprinters were similar in each phase of the 100-m run. The deterioration of the overall performance with age was primarily related to reduction in SL and increase in CT.

The objective of this study was to evaluate the short-term outcome of intranasal calcitonin treatment of elderly hip fracture patients on pain, bone loss, functional recovery, and length of hospital stay. In addition, we wanted to compare the effect of calcitonin with placebo on fusion of hip fractures treated with internal fixation using a screw or a nail. In a randomized, double-blind, clinically controlled trial, 260 independently living patients (aged 65 years or older) with acute hip fracture were randomly assigned to intranasal calcitonin 200 IU daily for 3 months or matching placebo nasal spray. Analyses were completed on an intention-to-treat basis. Three months after the operation, the median intensity of pain in visual analog scale was 0 mm (IQR 0.20) in the calcitonin group and 4 mm (IQR 0.33) in the placebo group (P = 0.15). The mean change in calcaneal bone mineral density from baseline to 3 months was not statistically significant between the groups -0.004 (95% CI -0.008 to -0.001) in the calcitonin group and -0.007 (95% CI -0.012 to -0.003) in the placebo group (P = 0.28). There were no significant differences in mortality, side effects, length of hospital stay, and functional recovery. Among patients with internal fixation using a screw or a nail (n = 99), fusion of the fracture was observed in an X-ray 3 months after the operation in 84% in the calcitonin group and in 63% in the placebo group (P = 0.029, difference 20% [95% CI 2 to 39]). We conclude that intranasal calcitonin might be useful for hip fracture patients but the clinical significance of this finding needs to be confirmed by studies with more participants, a longer treatment period, a longer follow-up, and perhaps a higher dose of calcitonin.

Background: there have been few population-based, randomized controlled trials on the effects of strength or endurance training on cardiovascular fitness in older women. Objective: to study the effects of strength or endurance training on cardiovascular fitness in women aged 76‐78 years. Design: a population-based, randomized controlled trial. Setting: exercise laboratory in a university faculty of sport and health sciences. Subjects: we randomly assigned 42 medically-screened women aged 76‐78 years, drawn from the population register to strength (n=16), endurance (n=15) or control (n=11) groups. Methods: subjects in the two exercise groups performed a supervised, individually tailored 18-week strength or endurance training programme. Controls continued with physical activity at their normal level. Results: the strength training group showed an increase in cycle ergometer peak power from 68.1 to 70.3 W (P=0.035 compared with controls). Their peak power per kg body weight increased from 1.02 to 1.05, while that of the endurance training group increased from 0.91 to 0.93 (P=0.027 and P=0.049 respectively). Peak oxygen uptake increased from 18.1 to 19.7 mlPkg 1 Pmin 1 in the strength and from 17.1 to 18.2 in the endurance group (nonsignificant). Six subjects (19%) in the exercise groups withdrew from the study because of health problems. Conclusions: even with its limitations, the study suggests that the effect of 18-week strength or endurance training on cardiovascular fitness among women aged 075 is relatively small. Furthermore, health problems can emerge during training programmes in medically-screened elderly women.

A 5-year follow-up study investigated serum concentrations of total (tOC) and intact (iOC) osteocalcin in relation to calcaneal bone mineral density (BMD). The study comprised two cohorts, 75- and 80-year-olds, both resident in the city of Jyvaskyla, Finland. Baseline OC and BMD were obtained for 161 men and 233 women, of whom 83 men and 189 women participated in follow-up bone measurements. The mean concentration of tOC increased from 9.6 +/- 4.3 to 13.2 +/- 8.5 microg/l (P = 0.001) in men and from 11.2 +/- 4.9 to 14.0 +/- 6.1 microg/l (P < 0.001) in women, whereas mean iOC decreased from 6.4 +/- 3.0 to 5.9 +/- 3.0 microg/l (P = 0.273) and from 7.7 +/- 3.7 to 6.9 +/- 3.4 microg/l (P = 0.021) in men and women, respectively. TOC and iOC levels correlated inversely with BMD and change in BMD in both sexes (r ranged from -0.223 to -0.422 and P = 0.048 < or = 0.001). When we divided the baseline tOC and iOC values into four quartiles, the decrease in BMD was significantly greater in the third tOC quartiles in women and in the fourth tOC and iOC quartiles in men when compared with the lower quartiles. During the 5-year period, 19 men and 59 women sustained at least one fracture. These individuals with fractures had significantly higher iOC values and tended to have higher tOC values compared with the nonfracture group at baseline (P = 0.038 and 0.087, respectively). Our results indicate that baseline serum tOC and iOC were associated with bone loss and predicted fracture in the two cohorts of independently living elderly men and women.

An age-related decline in muscle performance is a known risk factor for falling, fracture and disability. In women, a clear deterioration is observed from early menopause. The effect of hormone replacement therapy (HRT) in preserving muscle performance is, however, unclear. This trial examined the effects of a 12-month HRT and high-impact physical exercise regimen on skeletal muscle in women in early menopause. A total of 80 women aged 50–57 years were assigned randomly to one of four groups: exercise (Ex), HRT, exercise+HRT (ExHRT) and control (Co). The exercise groups participated in a high-impact training programme. The administration of HRT (oestradiol/noretisterone acetate) or placebo was carried out double-blind. Knee extension torque and vertical jumping height were evaluated. Lean tissue cross-sectional area (LCSA) and the relative proportion of fat within the muscle compartment were measured for the quadriceps and lower leg muscles. The ExHRT group showed significant increases in knee extension torque (8.3%) and vertical jumping height (17.2%) when compared with the Co group (-7.2%). Vertical jumping height also increased after HRT alone (6.8%). The LCSA of the quadriceps was increased significantly in the HRT (6.3%) and ExHRT (7.1%) groups when compared with the Ex (2.2%) and Co (0.7%) groups. Lower leg LCSA was also increased in the ExHRT group (9.1%) when compared with the Ex (3.0%) and Co (4.1%) groups. In addition, the increase in the relative proportion of fat in the quadriceps in the Co group (16.6%) was significant compared with those in the HRT (4.9%) and ExHRT (-0.6%) groups. Thus, in post-menopausal women, muscle performance, muscle mass and muscle composition are improved by HRT. The beneficial effects of HRT combined with high-impact physical training may exceed those of HRT alone.

Human serum contains two forms of tartrate-resistant acid phosphatase (TRAP), 5a and 5b. Of these, 5a contains sialic acid and 5b does not. We show here that antigenic properties and pH optimum of TRAP purified from human osteoclasts are identical to those of serum TRAP 5b and completely different from those of serum TRAP 5a, suggesting that 5b would be derived from osteoclasts and 5a from some other source. We developed a novel immunoassay specific for 5b using a monoclonal antibody O1A as capture antibody. O1A did not bind acid phosphatase derived from platelets and erythrocytes. Western analysis showed that O1A was specific for TRAP in both human bone and serum. We measured bound TRAP activity at pH 6.1, where 5b is highly active and 5a almost completely inactive. The immunoassay detected more than 90% of the initial TRAP 5b activity after 8-h incubation of serum samples at 25 degrees C and after 3 days incubation at 4 degrees C. Serum TRAP 5b activity decreased significantly after 6 months of hormone replacement therapy (HRT) of postmenopausal women compared with the change observed in postmenopausal women receiving placebo (p < 0.0001). Instead, no significant differences were observed between the changes in the placebo and HRT groups in total serum TRAP amount. These results show that serum TRAP 5b is a specific and sensitive marker for monitoring antiresorptive treatment. Instead, total serum TRAP cannot be used for that purpose. These findings may turn out to be a significant improvement in using serum TRAP as a resorption marker.

To study effort tolerance in elderly women with different physical activity backgrounds, 52 physically active (PA) and 42 sedentary control women (CO) aged 66-85 yr were assigned to perform cycle ergometer exercise to their volitional maximum. Oxygen uptake, respiratory exchange ratio (RER), heart rate, work power, and rate pressure product were measured to evaluate the severity of exercise. Plasma C-ANP (C-terminus of the atrial natriuretic peptide prohormone) and plasma N-ANP (N-terminus of the atrial natriuretic peptide prohormone) were analyzed as indicators of cardiac load. Eighty-one percent (N = 42) of the PA and 52% (N = 22) of CO performed the ergometer exercise. The mean peak oxygen uptake was 22.6 and 15.1 mL x kg(-1) x min(-1) among PA and CO, respectively. Twenty-two of the 42 PA and 19 of the 22 CO terminated the ergometer exercise before attaining the objective maximum. The most common reasons for termination were the subject's own wish, abnormal cardiovascular response, or lower limb tiredness. Both C-ANP and N-ANP increased after exercise. The increase in plasma C-ANP correlated significantly with a few physiological variables, whereas comparable associations with N-ANP were not found. It is concluded that inexperience of physical exertion and medical as well as physiological factors limit effort tolerance among elderly women. Differences in the response of C-ANP and N-ANP were found that are suggested to be due to differences in the postsecretory mechanisms between these hormones.

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 the control subjects, the proportion of smaller type I and type IIa fibres increased during the experimental period. The results indicate that intensive strength training induces type I fibre hypertrophy, whereas the effects of endurance training are less evident. The considerable variation found in the change in muscle fibre cross-sectional areas is also noteworthy.

A 5-year follow-up study investigated calcaneal bone mineral density (BMD) and changes in BMD in relation to fracture occurrence. The subjects comprised two cohorts born in 1914 and 1910 living in the city of Jyväskylä in central Finland. One hundred and three men (82%) and 188 women (73%), aged 75, and 57 men (74%) and 136 women (65%), aged 80, of the eligible population participated in the baseline bone measurements. The follow-up bone measurements were obtained for 59 men (68%) and 119 women (66%), aged 80 years, and for 21 men (53%) and 61 women (48%), aged 85 years. During the follow-up period, 8 men and 36 women from the younger and 11 men and 24 women from the older cohort sustained at least one fracture. When the baseline levels of BMD were related to fracture occurrence, the results clearly showed that with increased BMD values the probability of fracture decreased. Where men and women had similar BMD values, they also had a similar fracture probability. Except for one woman in the older cohort, none of those who had initial BMD values more than 1 standard deviation above the mean for their age developed a fracture during the follow-up period. The mean annual decrease in BMD was greater in the women (2.5-2.7%) than in the men (0.8-1.0%). The BMD change tended to associate with fracture occurrence only in the 75-year-old women (p = 0.075). The results suggest that calcaneus BMD can be used as a predictor of fracture occurrence in 75- to 80-year-old men and women. However, associating fractures with the change in BMD was difficult due to the limited number of survivors and initial differences in BMD values.

Objective: To develop quantitative ultrasonography in studying the adaptation of quadriceps muscle mass and composition to short-term physical training and rehabilitation in elderly women. Design: Randomized control trial. Setting: Measurements in a research laboratory and training in a fitness center and sports hall. Participants: Forty-two women, aged 76 to 78 years, with no indications against intensive physical exercise, randomly assigned to strength ( n = 16), endurance ( n = 15), and control ( n = 11) groups. Twelve subjects from the strength, 12 from the endurance, and 11 from the control group completed the study. Intervention: Supervised physical training 3 times a week for 18 weeks. Strength training: 3 to 4 sets of 8 to 10 repetitions with a load of 60% to 75% of the subjects' 1-repetition maximum. Endurance training: track walking and step aerobics at an intensity of 50% to 80% of maximum heart-rate reserve. Main Outcome Measures: Ultrasonographic measurements of the quadriceps cross-sectional area (CSA), thickness, and weighted mean grey shades of vastus lateralis (MGS vL ) and femur (MGS F ). Results: No significant interaction of group by time was observed in any of the outcome measures. The changes observed in CSA in the strength group correlated with those measured by computed tomography reported earlier. MGS VL decreased and MGS F increased in the strength group, suggesting a decreased proportion of fat in the muscle. Conclusions: Quantitative ultrasonography is a potentially useful tool for studying skeletal muscle in elderly women. The precision and accuracy of the method, however, should be improved to reveal the adaptation of aging muscles to short-term physical training and rehabilitation programs.

The separate effects of 18 weeks of intensive strength and endurance training on isometric knee extension (KE) and flexion (KF) strength and walking speed were studied in 76- to 78- year-old women. Maximal voluntary isometric force for both KE and KF was measured in a sitting position on a custom-made dynamometer chair at a knee angle of 60 degrees from full extension. Maximal walking speed was measured over a distance of 10 m. The endurance-trained women increased KE torque and KE torque/body mass after the first 9 weeks of training when compared with the controls. when comparing the baseline, 9 week and 18 week measurements within the groups separately, both the endurance- and strength-training groups increased KE torque, KE torque/body mass and walking speed. Individual changes in KE torque/body mass before and after 18 weeks of training averaged 19.1% in the strength group, 30.9% in the endurance group and 2.0% in the controls. This study indicates that in elderly women the effects of physical training on muscle strength and walking speed occur after endurance as well as strength training. The considerable interindividual variation in change of muscle performance is also worth noticing.