Skeletal muscle contractility and myosin function decline following ovariectomy in mature female mice. In the present study we tested the hypothesis that estradiol replacement can reverse those declines. Four-month-old female C57BL/6 mice (n = 69) were ovariectomized (OVX) or sham operated. Some mice were treated immediately with placebo or 17beta-estradiol (OVX + E(2)) while other mice were treated 30 days postsurgery. Thirty or sixty days postsurgery, soleus muscles were assessed in vitro for contractile function and susceptibility to eccentric contraction-induced injury. Myosin structural dynamics was analyzed in extensor digitorum longus (EDL) muscles by electron paramagnetic resonance spectroscopy. Maximal isometric tetanic force was affected by estradiol status (P < 0.001) being approximately 10% less in soleus muscles from OVX compared with sham-operated mice [168 mN (SD 16.7) vs. 180 mN (SD 14.4)] and was restored in OVX + E(2) mice [187 mN (SD 17.6)]. The fraction of strong-binding myosin during contraction was also affected (P = 0.045) and was approximately 15% lower in EDL muscles from OVX compared with OVX + E(2) mice [0.263 (SD 0.034) vs. 0.311 (SD 0.022)]. Plasma estradiol levels were correlated with maximal isometric tetanic force (r = 0.458; P < 0.001) and active stiffness (r = 0.329; P = 0.044), indicating that circulating estradiol influenced muscle and myosin function. Estradiol was not effective in protecting muscle against an acute eccentric contraction-induced injury (P >or= 0.401) but did restore ovariectomy-induced increases in muscle wet mass caused by fluid accumulation. Collectively, estradiol had a beneficial effect on female mouse skeletal muscle.
The purposes of this study were to determine the effects of ovarian hormone removal on force-generating capacities and contractile proteins in soleus and extensor digitorum longus (EDL) muscles of mature female mice. Six-month-old female C57BL/6 mice were randomly assigned to either an ovariectomized (OVX; n = 13) or a sham-operated (sham; n = 13) group. In vitro contractile function of soleus and EDL muscles were determined 60 days postsurgery. Total protein and contractile protein contents were quantified, and electron paramagnetic resonance (EPR) spectroscopy was used to determine myosin structural distribution during contraction. OVX mice weighed 15% more than sham mice 60 days postsurgery, and soleus and EDL muscle masses were 19 and 15% greater in OVX mice, respectively (P < or = 0.032). Soleus and EDL muscles from OVX mice generated less maximal isometric force than did those from sham mice [soleus: 0.27 (SD 0.04) vs. 0.22 N.cm.mg(-1) (SD 0.04); EDL: 0.33 (SD 0.04) vs. 0.27 N.cm.mg(-1) (SD 0.04); P < or = 0.006]. Total and contractile protein contents of soleus and EDL muscles were not different between OVX and sham mice (P > or = 0.242), indicating that the quantity of contractile machinery was not affected by removing ovarian hormones. EPR spectroscopy showed that the fraction of strong-binding myosin during contraction was 15% lower in EDL muscles from OVX mice compared with shams [0.277 (SD 0.039) vs. 0.325 (SD 0.020); P = 0.004]. These results indicate that the loss of ovarian hormones has detrimental effects on skeletal muscle force-generating capacities that can be explained by altered actin-myosin interactions.
Like other transforming growth factor-β (TGF-β) family members, myostatin is proteolytically cleaved into an N-terminal latency-associated protein (LAP) and a C-terminal mature protein, which recombine in a non-covalent manner before secretion. Despite the decrease in mature myostatin in muscle of male mice, there was an equal abundance of LAP in skeletal muscles of both sexes (McMahon et al. 2003a). Therefore, the reduced abundance of mature myostatin protein in males probably occurs after translation. At present, it is unclear how this post-translational decrease in mature myostatin protein in males is regulated. It is also unclear if the mechanism is activated before the linear growth phase to enhance development of muscle in young males or after the linear growth phase to maintain the greater musculature of adult males.
Values are mean (s.e.m.) (n= 6 per group). Asterisks indicate significance at each time point (*P < 0.05, ***P < 0.001). A representative Western blot is shown for myostatin LAP and mature protein for male and female mice at each age. The abundance of actin is shown to demonstrate the similarity in loading of protein per lane. Note, there was low protein in the samples collected at 2 weeks and actin was not detected in the representative female sample at this age.
Myostatin mRNA was reduced (P < 0.05) in gastrocnemius muscles of control Hypox mice and was restored to that of sham-Hypox controls 120 min after injection of GH (Fig. 4). In contrast, abundance of mature myostatin protein was higher in muscles of control Hypox mice and was reduced to that of sham-Hypox controls 120 min after injection of GH (Fig. 4). The abundance of LAP had a similar pattern to that of mature myostatin, but differences were not significant (Fig. 4).
Values are mean (s.e.m.) (n= 6 per group). Unlike letters indicate a significant difference among groups (a,bP < 0.001). A representative Western blot is shown for myostatin LAP and mature protein for each sex and genotype. The abundance of actin was assessed to demonstrate the similarity in loading of protein per lane.
We speculate that the decrease in mature myostatin protein occurs after translation because there is less in male gastrocnemius, but an equal abundance of LAP in males and females. However, we do not discount the possibility that a decrease in translation is also occurring. Indeed, while there is increased myostatin mRNA in male gastrocnemius, there is an equal amount of LAP in males and females, which could be explained by a decrease in translation in males. To address the potential mechanism, we provide evidence that GH induces the decrease in mature myostatin protein. It is interesting to note that the abundance of LAP tended to have a similar pattern to that of mature myostatin after injection of GH in hypophysectomised mice, which suggests that GH may mediate a similar reduction in the abundance of LAP, albeit to a lesser extent than the mature protein. The similar abundance of LAP between the sexes suggests that LAP is maintained at a constant amount in an age-dependent manner. The reason for this is unclear, but may relate to the fact that LAP also promotes the development of skeletal muscle in male and female mice (Yang et al. 2001). Therefore, a decrease in LAP would be detrimental to development of skeletal muscle and sexually dimorphic growth.
Lobo RA. Menopause and care of the mature woman: endocrinology, consequences of estrogen deficiency, effects of hormone therapy, and other treatment options. In: Lobo RA, Gershenson DM, Lentz GM, Valea FA, eds. Comprehensive Gynecology. 7th ed. Philadelphia, PA: Elsevier; 2017:chap 14.
How well organs function depends on how well the cells within them function. Older cells function less well. Also, in some organs, cells die and are not replaced, so the number of cells decreases. The number of cells in the testes, ovaries, liver, and kidneys decreases markedly as the body ages. When the number of cells becomes too low, an organ cannot function normally. Thus, most organs function less well as people age. However, not all organs lose a large number of cells. The brain is one example. Healthy older people do not lose many brain cells. Substantial losses occur mainly in people who have had a stroke Overview of Stroke A stroke occurs when an artery to the brain becomes blocked or ruptures, resulting in death of an area of brain tissue due to loss of its blood supply (cerebral infarction) and symptoms that... read more or who have a disorder that causes the progressive loss of nerve cells (neurodegenerative disorders), such as Alzheimer disease Alzheimer Disease Alzheimer disease is a progressive loss of mental function, characterized by degeneration of brain tissue, including loss of nerve cells, the accumulation of an abnormal protein called beta-amyloid... read more or Parkinson disease Parkinson Disease (PD) Parkinson disease is a slowly progressive degenerative disorder of specific areas of the brain. It is characterized by tremor when muscles are at rest (resting tremor), increased muscle tone... read more .
The amount of muscle tissue (muscle mass) and muscle strength tend to decrease beginning around age 30 and continuing throughout life. Some of the decrease is caused by physical inactivity and decreasing levels of growth hormone and testosterone, which stimulate muscle development. Also, muscles cannot contract as quickly because more fast-contracting (fast-twitch) muscle fibers are lost than slow-contracting (slow-twitch) muscle fibers. However, aging's effects reduce muscle mass and strength by no more than about 10 to 15% during an adult's lifetime. In the absence of disease, most of the loss beyond that 10 to 15% is preventable with regular exercise. More severe muscle loss (called sarcopenia, which literally means loss of flesh) results from disease or extreme inactivity, not from aging alone.
Regular exercise Exercise in Older Adults At least 75% of people over age 65 do not exercise at recommended levels despite the known health benefits of exercise including Longer survival Improved quality of life (for example, endurance... read more to strengthen muscles (resistance training) can partially overcome or significantly delay loss of muscle mass and strength. In muscle-strengthening exercise, muscles contract against resistance provided by gravity (as in sit-ups or push-ups), weights, or rubber bands. If this type of exercise is done regularly, even people who have never exercised can increase muscle mass and strength. Conversely, physical inactivity, especially bed rest during an illness, can greatly accelerate the loss. During periods of inactivity, older people lose muscle mass and strength much more quickly than younger people do. For example, to make up for the muscle mass lost during each day of strict bed rest, people may need to exercise for up to 2 weeks. 59ce067264