The purpose of this Position Stand is to provide an overview of issues critical to understanding the importance of exercise and physical activity in older adult populations. The Position Stand is divided into three sections: Section 1 briefly reviews the structural and functional changes that characterize normal human aging, Section 2 considers the extent to which exercise and physical activity can influence the aging process, and Section 3 summarizes the benefits of both long-term exercise and physical activity and shorter-duration exercise programs on health and functional capacity. Although no amount of physical activity can stop the biological aging process, there is evidence that regular exercise can minimize the physiological effects of an otherwise sedentary lifestyle and increase active life expectancy by limiting the development and progression of chronic disease and disabling conditions. There is also emerging evidence for significant psychological and cognitive benefits accruing from regular exercise participation by older adults. Ideally, exercise prescription for older adults should include aerobic exercise, muscle strengthening exercises, and flexibility exercises. The evidence reviewed in this Position Stand is generally consistent with prior American College of Sports Medicine statements on the types and amounts of physical activity recommended for older adults as well as the recently published 2008 Physical Activity Guidelines for Americans. All older adults should engage in regular physical activity and avoid an inactive lifestyle.

Exercise and physical activity for older adults

Background Although disuse of skeletal muscle and undernutrition are often cited as potentially reversible causes of frailty in elderly people, the efficacy of interventions targeted specifically at these deficits has not been carefully studied. Methods We conducted a randomized, placebo-controlled trial comparing progressive resistance exercise training, multinutrient supplementation, both interventions, and neither in 100 frail nursing home residents over a 10-week period. Results The mean (±SE) age of the 63 women and 37 men enrolled in the study was 87.1 ±0.6 years (range, 72 to 98); 94 percent of the subjects completed the study. Muscle strength increased by 113 ±8 percent in the subjects who underwent exercise training, as compared with 3 ±9 percent in the nonexercising subjects (P<0.001). Gait velocity increased by 11.8 ±3.8 percent in the exercisers but declined by 1.0 ±3.8 percent in the nonexercisers (P = 0.02). Stair-climbing power also improved in the exercisers as compared with the nonexercis...

https://www.nejm.org/doi/pdf/10.1056/NEJM199406233302501

Exercise training and nutritional supplementation for physical frailty in very elderly people

The goal of this review is to present a comprehensive survey of the many intriguing facets of creatine (Cr) and creatinine metabolism, encompassing the pathways and regulation of Cr biosynthesis an...

http://www.afboard.com/library/creatinemetabolism.pdf

Creatine and Creatinine Metabolism

Mammalian skeletal muscle comprises different fiber types, whose identity is first established during embryonic development by intrinsic myogenic control mechanisms and is later modulated by neural and hormonal factors. The relative proportion of the different fiber types varies strikingly between species, and in humans shows significant variability between individuals. Myosin heavy chain isoforms, whose complete inventory and expression pattern are now available, provide a useful marker for fiber types, both for the four major forms present in trunk and limb muscles and the minor forms present in head and neck muscles. However, muscle fiber diversity involves all functional muscle cell compartments, including membrane excitation, excitation-contraction coupling, contractile machinery, cytoskeleton scaffold, and energy supply systems. Variations within each compartment are limited by the need of matching fiber type properties between different compartments. Nerve activity is a major control mechanism of the fiber type profile, and multiple signaling pathways are implicated in activity-dependent changes of muscle fibers. The characterization of these pathways is raising increasing interest in clinical medicine, given the potentially beneficial effects of muscle fiber type switching in the prevention and treatment of metabolic diseases.

Fiber types in mammalian skeletal muscles.

Aging is associated with progressive loss of neuromuscular function that often leads to progressive disability and loss of independence. The term sarcopenia is now commonly used to describe the loss of skeletal muscle mass and strength that occurs in concert with biological aging. By the seventh and eighth decade of life, maximal voluntary contractile strength is decreased, on average, by 20-40% for both men and women in proximal and distal muscles. Although age-associated decreases in strength per unit muscle mass, or muscle quality, may play a role, the majority of strength loss can be accounted for by decreased muscle mass. Multiple factors lead to the development of sarcopenia and the associated impact on function. Loss of skeletal muscle fibers secondary to decreased numbers of motoneurons appears to be a major contributing influence, but other factors, including decreased physical activity, altered hormonal status, decreased total caloric and protein intake, inflammatory mediators, and factors leading to altered protein synthesis, must also be considered. The prevalence of sarcopenia, which may be as high as 30% for those ≥60 yr, will increase as the percentage of the very old continues to grow in our populations. The link between sarcopenia and disability among elderly men and women highlights the need for continued research into the development of the most effective interventions to prevent or at least partially reverse sarcopenia, including the role of resistance exercise and other novel pharmacological and nutritional interventions.

Invited review: Aging and sarcopenia.

Mammalian skeletal muscles consist of three main fibre types, type 1, 2A and 2B fibres, with different myosin heavy chain (MHC) composition. We have now identified another fibre type, called type 2X fibre, characterized by a specific MHC isoform. Type 2X fibres, which are widely distributed in rat skeletal muscles, can be distinguished from 2A and 2B fibres by histochemical ATPase activity and by their unique staining pattern with seven anti-MHC monoclonal antibodies. The existence of the 2X-MHC isoform was confirmed by immunoblotting analysis using muscles containing 2X fibres as a major component, such as the normal and hyperthyroid diaphragm, and the soleus muscle after high frequency chronic stimulation. 2X-MHC contains one determinant common to 2B-MHC and another common to all type 2-MHCs, but lacks epitopes specific for 2A- and 2B-MHCs, as well as an epitope present on all other MHCs. By SDS-polyacrylamide gel electrophoresis 2X-MHC shows a lower mobility compared to 2B-MHC and appears to comigrate with 2A-MHC. Muscles containing predominantly 2X-MHC display a velocity of shortening intermediate between that of slow muscles and that of fast muscles composed predominantly of 2B fibres.

Three myosin heavy chain isoforms in type 2 skeletal muscle fibres.

The function and morphology of knee extension/m. vastus lateralis and elbow flexion/m. biceps brachii were studied in young (28 +/- 0.1 years, n = 7) and elderly (68 +/- 0.5 years, n = 8) sedentary subjects and in elderly swimmers (69 +/- 1.9 years, n = 6), runners (70 +/- 0.7 years, n = 5) and strength-trained subjects (68 +/- 0.8 years, n = 7). On average, the training groups had, for the 12-17 years before the measurements were taken, performed their training regimen 3 +/- 0.1 times a week. Compared with the young subjects, the maximal isometric torque of the sedentary elderly subjects was 44% (P less than 0.05) lower in knee extension and 32% (P less than 0.05) lower in elbow flexion, and speed of movement was between 20 and 26% (P less than 0.05) lower in both knee extension and elbow flexion. The cross-sectional area of m. quadriceps femoris and the elbow flexors was also 24% (P less than 0.05) and 20% lower respectively, and the specific tension was 27% (P less than 0.05) lower in m. quadriceps femoris and 14% (P less than 0.05) lower in the elbow flexors. A 27% (P less than 0.05) higher content of myosin heavy chain type I and a 39% (P less than 0.05) higher content of the slow-type myosin light chain--2 was observed in m. vastus lateralis of the sedentary elderly subjects as compared with the young subjects. The same tendency was also seen with m. biceps brachii. Since the histochemical fibre-type distribution was identical and no major co-expression of type I and type II myosin heavy-chain isoforms was observed with immunocytochemistry, the increase in slow myosin isoforms with ageing seems mainly related to a larger relative area of type I fibres, induced by a selective atrophy of type II fibre area. An increased content of the beta-isoform of tropomyosin was also demonstrated with ageing. In contrast to the swimmers and runners, the elderly strength-trained subjects had maximal isometric torques, speed of movements, cross-sectional areas, specific tensions and a content of myosin and tropomyosin isoforms in both muscles studied identical to those of the young controls. These results seem to suggest that strength training can counteract the age-related changes in function and morphology of the ageing human skeletal muscle.

Function, morphology and protein expression of ageing skeletal muscle: a cross-sectional study of elderly men with different training backgrounds.

A novel type of myosin heavy chain (MHC), called 2X, has been recently identified in type 2 fibers of rat skeletal muscles using an immunochemical approach. In the present study, the same panel of anti-MHC monoclonal antibodies was used in immunohistochemistry combined with enzyme histochemistry to identify and compare type 2X fibers in hindlimb skeletal muscles of rat, mouse, and guinea pig. Immunohistochemistry shows that 2X MHC is localized in a large subset of type 2 fibers and is co-expressed with 2A or 2B MHC in a small number of fibers. Enzyme histochemistry shows that type 2X fibers display low myosin ATPase activity after pre-incubation at pH 4.3 and high activity after paraformaldehyde pre-incubation at pH 10.4. After pre-incubation at pH 4.6, myosin ATPase shows intermediate and high activity in rat and mouse 2X fibers, respectively, whereas it is low in guinea pig 2X fibers. Succinate dehydrogenase displays moderate to high activity in 2X fibers of all species. Taken together, these staining patterns allow this novel fiber population to be distinguished from the other type 2 fibers using only enzyme histochemistry. Nevertheless, the combined use of immuno- and enzyme histochemistry prevents incorrect fiber typing due to the interspecies variability of myosin ATPase activity among the correspondent fiber types, and completely modifies the presently used classification of mouse type 2 fibers.

Identification of a novel type 2 fiber population in mammalian skeletal muscle by combined use of histochemical myosin ATPase and anti-myosin monoclonal antibodies.

The expression of 4 myosin heavy chain (MHC) isoforms was analyzed in the rat soleus (SOL) and extensor digitorum longus (EDL) muscles after denervation and chronic electric stimulation The stimulation frequencies used were 20 and 150 Hz and the amount of stimulation was either large (20 Hz), intermediate (150 Hz), or small (150 Hz) These patterns resemble some features of normal motor unit activity in SOL and EDL of freely moving rats (Hennig and Lomo, 1985) The relative expression of each MHC isoform depended strongly on the stimulation pattern Furthermore, for any particular stimulation pattern, fibers in SOL and EDL expressed different MHCs Coexistence of different MHC types in the same fiber was frequently observed in stimulated muscles 20-Hz stimulation preserved normal expression of type 1-MHC in SOL but failed to induce type 1-MHC in type 2 fibers of the EDL, where type 2A- and 2X-MHC expression dominated and type 2B-MHC expression was completely suppressed 150-Hz low-amount stimulation preserved nearly normal 2B-MHC expression in many type 2 fibers of the EDL but failed to induce type 2B-MHC expression in the SOL, where 2X-MHC became predominant 150-Hz high-amount stimulation differed from 150-Hz small amount stimulation by suppressing almost all type 2B-MHC expression in EDL and by inducing considerable type 2A-MHC expression in the SOL Scattered fibers in EDL that were probably the original type 1 fibers responded differently from both type 2 fibers in the EDL and from type 1 fibers in the SOL to stimulation(ABSTRACT TRUNCATED AT 250 WORDS)

https://www.jneurosci.org/content/jneuro/10/1/153.full.pdf

Expression of myosin heavy chain isoforms in stimulated fast and slow rat muscles.

We have previously reported the identification of a distinct myosin heavy chain (MyHC) isoform in a major subpopulation of rat skeletal muscle fibers, referred to as 2X fibers (Schiaffino, S., L. Gorza, S. Sartore, L. Saggin, M. Vianello, K. Gundersen, and T. Lomo. 1989. J. Muscle Res. Cell Motil. 10:197-205). However, it was not known whether 2X-MyHC is the product of posttranslational modification of other MyHCs or is coded by a distinct mRNA. We report here the isolation and characterization of cDNAs coding a MyHC isoform that is expressed in type 2X skeletal muscle fibers. 2X-MyHC transcripts differ from other MyHC transcripts in their restriction map and 3' end sequence and are thus derived from a distinct gene. In situ hybridization analyses show that 2X-MyHC transcripts are expressed at high levels in the diaphragm and fast hindlimb muscles and can be coexpressed either with 2B- or 2A-MyHC transcripts in a number of fibers. At the single fiber level the distribution of each MyHC mRNA closely matches that of the corresponding protein, determined by specific antibodies on serial sections. In hindlimb muscles 2X-, 2A-, and 2B-MyHC transcripts are first detected by postnatal day 2-5 and display from the earliest stages a distinct pattern of distribution in different muscles and different fibers. The emergence of type 2 MyHC isoforms thus defines a distinct neonatal phase of fiber type differentiation during muscle development. The functional significance of MyHC isoforms is discussed with particular reference to the velocity of shortening of skeletal muscle fibers.

https://rupress.org/jcb/article-pdf/123/4/823/1260825/823.pdf

Luisa Gorza

Papers

Three myosin heavy chain isoforms in type 2 skeletal muscle fibres.

Function, morphology and protein expression of ageing skeletal muscle: a cross-sectional study of elderly men with different training backgrounds.

Identification of a novel type 2 fiber population in mammalian skeletal muscle by combined use of histochemical myosin ATPase and anti-myosin monoclonal antibodies.

Expression of myosin heavy chain isoforms in stimulated fast and slow rat muscles.

Type 2X-myosin heavy chain is coded by a muscle fiber type-specific and developmentally regulated gene.