Stuart A. Bruce

In mice, the muscle weakness due to age is absent during stretching.

1. The contractile force was compared in isolated soleus muscles from young (2.5‐8 months old) and aged (28‐31 months old) mice. Force was measured at 25 degrees C during isometric tetanic contractions during isovelocity stretching and shortening contractions. 2. The normalized isometric force was lower by 13.3% in muscles from aged mice. Muscles from young and aged mice produced 0.951 +/‐ 0.031 N mg‐1 (n = 12) and 0.824 +/‐ 0.048 N mg‐1 (n = 9) respectively. The relaxation time, from 90 to 10% of the tetanic force, of muscles from aged mice was 102.1 +/‐ 3.7 ms (n = 6), which was longer than that for muscles from young mice, 84.4 +/‐ 3.8 ms (n = 6) (means +/‐ S.E.M.). 3. The force during shortening was also reduced in muscles from aged animals by the same proportion as the isometric force. Therefore the force during shortening relative to the isometric force was the same in muscles from young and aged mice. 4. During rapid stretching soleus muscles from aged mice produced a similar force to those from young mice. Therefore stretch can remove the weakness in muscles of aged mice. 5. These changes in muscles from aged mice are similar to those produced when inorganic phosphate (Pi) levels are raised, in skinned rabbit psoas fibres, or during fatigue or with low intracellular pH (pHi), in frog muscle. It is possible therefore that the force loss due to ageing may be due to a higher Pi level or a lower pHi.

Angiotensin-I converting enzyme genotype-dependent benefit from hormone replacement therapy in isometric muscle strength and bone mineral density.

Low bone mineral density (BMD) and muscle weakness are major risk factors for postmenopausal osteoporotic fracture. Hormone replacement therapy (HRT) reverses the menopausal decline in maximum voluntary force of the adductor pollicis and reduces serum angiotensin-I converting enzyme (ACE) levels. The insertion (I) allele of the ACE gene polymorphism is associated with lower ACE activity and improved muscle efficiency in response to physical training. Therefore, we examined whether the presence of the I allele in postmenopausal women would affect the muscle response to HRT. Those taking HRT showed a significant gain in normalized muscle maximum voluntary force slope, the rate of which was strongly influenced by ACE genotype (16.0 +/- 1.53%, 14.3 +/- 2.67%, and 7.76 +/- 4.13%, mean +/- SEM for II, ID, and DD genotype, respectively; P = 0.017 for gene effect, P = 0.004 for I allele effect). There was also a significant ACE gene effect in the response of BMD to HRT in Wards triangle (P = 0.03) and a significant I allele effect in the spine (P = 0.03), but not in the neck of femur or total hip. These data suggests that low ACE activity associated with the I allele confers an improved muscle and BMD response in postmenopausal women treated with HRT.

Interpreting the relation between force and cross-sectional area in human muscle

The maximum force a muscle can produce depends on its cross-sectional area (CSA). However, the exact interpretation of this relationship has been a matter of controversy. Recently, the controversy has centered on whether the measurements are best correlated using regression analysis or ratio standards. Applying regression analysis to this problem implies that all the experimental error is in the measurement of force. Thus, confusion may arise by failure to take account of errors in the measurement of CSA. Using a statistical model, we show how regression analysis can be misleading as error is introduced into the measurement of CSA as well as that of force. Because neither the errors in force nor CSA can be quantified in the experimental situation, we conclude that ratio standards are less likely to mislead although the accuracy of the result depends on the degree of correlation between force and CSA in the muscle measured.

Changes in isometric force of mouse soleus muscle during the oestrous cycle

Abstract Muscles excised from young female mice at known phases of the oestrous cycle were studied in vitro to determine if there are variations in force analogous to those that occur in vivo during the menstrual cycle in women. Oestrous phase was determined from vaginal smears. The maximum isometric and eccentric forces of pairs of isolated soleus muscles were measured. The first muscle was studied immediately after dissection, the second after incubation in Ringer solution for up to 2 h. Normalised isometric muscle force in the first muscle of each pair depended on the oestrous phase, the force being greatest during dioestrus. There was a negative correlation between normalised force and the eccentric/isometric force ratio. Neither of these phenomena was found with the second muscle of each pair. These results show that in mouse soleus muscle cross-bridge function does vary according to the phase of the oestrous cycle. However, the rise in force does not follow the pattern of the rise in blood oestrogen levels as it does in humans, and in the mouse the effect on cross-bridge function washes out after a few hours in vitro.