Susan V. Brooks

Bio: Susan V. Brooks is an academic researcher from University of Michigan. The author has contributed to research in topics: Skeletal muscle & Isometric exercise. The author has an hindex of 48, co-authored 130 publications receiving 8373 citations.

Contractile properties of skeletal muscles from young, adult and aged mice.

Abstract: 1 Comparisons were made in vitro at 25 degrees C among soleus and extensor digitorum longus (EDL) muscles from young (2-3 months), adult (9-10 months), and aged (26-27 months) male mice We tested the hypotheses that, compared with soleus and EDL muscles of young and adult mice, those from aged mice develop decreased maximum tetanic force (P0, mN) and specific P0 (N/cm2), and that no significant differences occur for contraction time, half-relaxation time, or force-velocity relationship 2 For the aged mice, the P0 of the soleus muscles and EDL muscles were 78 and 73% respectively of the values for adult mice The specific P0 of EDL muscles of aged mice was 78% of the value of 23 N/cm2 obtained for young and adult mice For soleus muscles, the specific P0 of 21 N/cm2 did not change with age 3 Compared to values for young and adult mice, the contraction and half-relaxation times of soleus muscles from aged mice were increased, but the overall force-velocity relationships of soleus and EDL muscles did not change The pooled values for the maximum velocity of unloaded shortening extrapolated from the force-velocity relationship of soleus and EDL muscles were 46 and 101 fibre lengths/s, respectively 4 The decrease in the specific P0 of the EDL muscle with ageing must result from either a decrease in the number of cross-bridges in the driving stroke or a decrease in the force developed by each cross-bridge

Age-related changes in the structure and function of skeletal muscles

Abstract: 1. For animals of all ages, during activation of skeletal muscles and the subsequent contraction, the balance between the force developed by the muscle and the external load determines whether the muscle shortens, remains at fixed length (isometric) or is lengthened. With maximum activation, the force developed is least during shortening, intermediate when muscle length is fixed and greatest during lengthening contractions. During lengthening contractions, when force is high, muscles may be injured by the contractions. 2. 'Frailty' and 'failure to thrive' are most frequently observed in elderly, physically inactive people. A 'frail' person is defined as one of small stature, with muscles that are atrophied, weak and easily fatigued. The condition of 'failure to thrive' is typified by a lack of response to well-designed programmes of nutrition and physical activity. 3. With ageing, skeletal muscle atrophy in humans appears to be inevitable. A gradual loss of muscle fibres begins at approximately 50 years of age and continues such that by 80 years of age, approximately 50% of the fibres are lost from the limb muscles that have been studied. For both humans and rats, the observation that the timing and magnitude of the loss of motor units is similar to that for muscle fibres suggests that the mechanism responsible for the loss of fibres and the loss of whole motor units is the same. The degree of atrophy of the fibres that remain is largely dependent on the habitual level of physical activity of the individual. 4. 'Master athletes' maintain a high level of fitness throughout their lifespan. Even among master athletes, performance of marathon runners and weight lifters declines after approximately 40 years of age, with peak levels of performance decreased by approximately 50% by 80 years of age. The success of the master athletes and of previously sedentary elderly who undertake well-designed, carefully administered training programmes provide dramatic evidence that age-associated atrophy, weakness and fatigability can be slowed, but not halted.

Rapamycin slows aging in mice.

Abstract: Rapamycin increases lifespan in mice, but whether this represents merely inhibition of lethal neoplastic diseases, or an overall slowing in multiple aspects of aging is currently unclear. We report here that many forms of age-dependent change, including alterations in heart, liver, adrenal glands, endometrium, and tendon, as well as age-dependent decline in spontaneous activity, occur more slowly in rapamycin-treated mice, suggesting strongly that rapamycin retards multiple aspects of aging in mice, in addition to any beneficial effects it may have on neoplastic disease. We also note, however, that mice treated with rapamycin starting at 9 months of age have significantly higher incidence of testicular degeneration and cataracts; harmful effects of this kind will guide further studies on timing, dosage, and tissue-specific actions of rapamycin relevant to the development of clinically useful inhibitors of TOR action.

Modular flexibility of dystrophin: Implications for gene therapy of Duchenne muscular dystrophy

Abstract: Attempts to develop gene therapy for Duchenne muscular dystrophy (DMD) have been complicated by the enormous size of the dystrophin gene. We have performed a detailed functional analysis of dystrophin structural domains and show that multiple regions of the protein can be deleted in various combinations to generate highly functional mini- and micro-dystrophins. Studies in transgenic mdx mice, a model for DMD, reveal that a wide variety of functional characteristics of dystrophy are prevented by some of these truncated dystrophins. Muscles expressing the smallest dystrophins are fully protected against damage caused by muscle activity and are not morphologically different from normal muscle. Moreover, injection of adeno-associated viruses carrying micro-dystrophins into dystrophic muscles of immunocompetent mdx mice results in a striking reversal of histopathological features of this disease. These results demonstrate that the dystrophic pathology can be both prevented and reversed by gene therapy using micro-dystrophins.

Skeletal muscle weakness in old age : Underlying mechanisms

Abstract: Maintenance of muscle mass and strength contributes to mobility which impacts on quality of life. Although muscle atrophy, declining strength, and physical frailty are generally accepted as inevitable concomitants of aging, the causes are unknown. Clarification of the mechanisms responsible for these changes would enhance our understanding of the degree to which they are preventable or treatable. The decline in muscle function between maturity and old age is similar for muscles of many different animals including human beings, and is typified by the decreases of approximately 35% in maximum force, approximately 30% in maximum power, and 20% in normalized force (kN.m-2) and power (W.kg-1) of extensor digitorum longus (EDL) muscles in old compared with adult mice. Much of the age-associated muscle atrophy and declining strength may be explained by motor unit remodeling which appears to occur by selective denervation of muscle fibers with reinnervation by axonal sprouting from an adjacent innervated unit. Muscles in old mice appear more susceptible to injury than muscles in young or adult mice and have a decreased capacity for recovery. The process of age-related denervation may be aggravated by an increased susceptibility of muscles in old animals to contraction-induced injury coupled with impaired capacity for regeneration.

American College of Sports Medicine Position Stand. Progression Models in Resistance Training for Healthy Adults

Abstract: In order to stimulate further adaptation toward a specific training goal(s), progression in the type of resistance training protocol used is necessary. The optimal characteristics of strength-specific programs include the use of both concentric and eccentric muscle actions and the performance of both single- and multiple-joint exercises. It is also recommended that the strength program sequence exercises to optimize the quality of the exercise intensity (large before small muscle group exercises, multiple-joint exercises before single-joint exercises, and higher intensity before lower intensity exercises). For initial resistances, it is recommended that loads corresponding to 8-12 repetition maximum (RM) be used in novice training. For intermediate to advanced training, it is recommended that individuals use a wider loading range, from 1-12 RM in a periodized fashion, with eventual emphasis on heavy loading (1-6 RM) using at least 3-min rest periods between sets performed at a moderate contraction velocity (1-2 s concentric, 1-2 s eccentric). When training at a specific RM load, it is recommended that 2-10% increase in load be applied when the individual can perform the current workload for one to two repetitions over the desired number. The recommendation for training frequency is 2-3 d x wk(-1) for novice and intermediate training and 4-5 d x wk(-1) for advanced training. Similar program designs are recommended for hypertrophy training with respect to exercise selection and frequency. For loading, it is recommended that loads corresponding to 1-12 RM be used in periodized fashion, with emphasis on the 6-12 RM zone using 1- to 2-min rest periods between sets at a moderate velocity. Higher volume, multiple-set programs are recommended for maximizing hypertrophy. Progression in power training entails two general loading strategies: 1) strength training, and 2) use of light loads (30-60% of 1 RM) performed at a fast contraction velocity with 2-3 min of rest between sets for multiple sets per exercise. It is also recommended that emphasis be placed on multiple-joint exercises, especially those involving the total body. For local muscular endurance training, it is recommended that light to moderate loads (40-60% of 1 RM) be performed for high repetitions (> 15) using short rest periods (< 90 s). In the interpretation of this position stand, as with prior ones, the recommendations should be viewed in context of the individual's target goals, physical capacity, and training status.

Cellular and Molecular Regulation of Muscle Regeneration

Abstract: Charge, Sophie B. P., and Michael A. Rudnicki. Cellular and Molecular Regulation of Muscle Regeneration. Physiol Rev 84: 209–238, 2004; 10.1152/physrev.00019.2003.—Under normal circumstances, mamma...

Progress and problems with the use of viral vectors for gene therapy

Abstract: Gene therapy has a history of controversy. Encouraging results are starting to emerge from the clinic, but questions are still being asked about the safety of this new molecular medicine. With the development of a leukaemia-like syndrome in two of the small number of patients that have been cured of a disease by gene therapy, it is timely to contemplate how far this technology has come, and how far it still has to go.