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

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.

Assessing mitochondrial dysfunction requires definition of the dysfunction to be investigated. Usually, it is the ability of the mitochondria to make ATP appropriately in response to energy demands. Where other functions are of interest, tailored solutions are required. Dysfunction can be assessed in isolated mitochondria, in cells or in vivo, with different balances between precise experimental control and physiological relevance. There are many methods to measure mitochondrial function and dysfunction in these systems. Generally, measurements of fluxes give more information about the ability to make ATP than do measurements of intermediates and potentials. For isolated mitochondria, the best assay is mitochondrial respiratory control: the increase in respiration rate in response to ADP. For intact cells, the best assay is the equivalent measurement of cell respiratory control, which reports the rate of ATP production, the proton leak rate, the coupling efficiency, the maximum respiratory rate, the respiratory control ratio and the spare respiratory capacity. Measurements of membrane potential provide useful additional information. Measurement of both respiration and potential during appropriate titrations enables the identification of the primary sites of effectors and the distribution of control, allowing deeper quantitative analyses. Many other measurements in current use can be more problematic, as discussed in the present review.

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Assessing mitochondrial dysfunction in cells

Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance

The present study examines age-related changes in skeletal muscle size and function after 12 yr. Twelve healthy sedentary men were studied in 1985–86 (T1) and nine (initial mean age 65.4 ± 4.2 yr) ...

Aging of skeletal muscle: a 12-yr longitudinal study

This study determined the decline in oxidative capacity per volume of human vastus lateralis muscle between nine adult (mean age 38.8 years) and 40 elderly (mean age 68.8 years) human subjects (age range 25-80 years). We based our oxidative capacity estimates on the kinetics of changes in creatine phosphate content ([PCr]) during recovery from exercise as measured by (31)P magnetic resonance (MR) spectroscopy. A matched muscle biopsy sample permitted determination of mitochondrial volume density and the contribution of the loss of mitochondrial content to the decline in oxidative capacity with age. The maximal oxidative phosphorylation rate or oxidative capacity was estimated from the PCr recovery rate constant (k(PCr)) and the [PCr] in accordance with a simple electrical circuit model of mitochondrial respiratory control. Oxidative capacity was 50 % lower in the elderly vs. the adult group (0.61 +/- 0.04 vs. 1.16 +/- 0.147 mM ATP s(-1)). Mitochondrial volume density was significantly lower in elderly compared with adult muscle (2.9 +/- 0.15 vs. 3.6 +/- 0.11 %). In addition, the oxidative capacity per mitochondrial volume (0.22 +/- 0.042 vs. 0.32 +/- 0.015 mM ATP (s %)(-1)) was reduced in elderly vs. adult subjects. This study showed that elderly subjects had nearly 50 % lower oxidative capacity per volume of muscle than adult subjects. The cellular basis of this drop was a reduction in mitochondrial content, as well as a lower oxidative capacity of the mitochondria with age.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1469-7793.2000.t01-1-00203.x

Oxidative capacity and ageing in human muscle

In response to growth factors, mTOR (mammalian target of rapamycin) has been identified as a central component of the signalling pathways that control the translational machinery and cell growth. Signalling through mTOR has also been shown to be necessary for the mechanical load-induced growth of cardiac and skeletal muscles. Although the mechanisms involved for mechanically induced activation of mTOR are not known, it has been suggested that activation of PI3K (phosphoinositide 3-kinase) and protein kinase B (Akt), via the release of locally acting growth factors, underlies this process. In the present study, we show that mechanically stimulating (passive stretch) the skeletal muscle ex vivo results in the activation of mTOR-dependent signalling events. The activation of mTOR-dependent signalling events was necessary for an increase in translational efficiency, demonstrating the physiological significance of this pathway. Using pharmacological inhibitors, we show that activation of mTOR-dependent signalling occurs through a PI3K-independent pathway. Consistent with these results, mechanically induced signalling through mTOR was not disrupted in muscles from Akt1−/− mice. In addition, ex vivo co-incubation experiments, along with in vitro conditioned-media experiments, demonstrate that a mechanically induced release of locally acting autocrine/paracrine growth factors was not sufficient for the activation of the mTOR pathway. Taken together, our results demonstrate that mechanical stimuli can activate the mTOR pathway independent of PI3K/Akt1 and locally acting growth factors. Thus mechanical stimuli and growth factors provide distinct inputs through which mTOR co-ordinates an increase in the translational efficiency.

/pdf/mechanical-stimuli-regulate-rapamycin-sensitive-signalling-1a3mgqoodw.pdf

Mechanical stimuli regulate rapamycin-sensitive signalling by a phosphoinositide 3-kinase-, protein kinase B- and growth factor-independent mechanism.

1. The chemical changes during contractile activity were separated from recovery metabolism in the forearm flexor musculature in normal human subjects using 31P nuclear magnetic resonance (NMR) spectroscopy. Percutaneous, supramaximal twitch stimulation of the median and ulnar nerves was used in combination with temporary ischaemia of the forearm to characterize the summed ATPase activity. The recovery following restoration of blood flow provided a measure of oxidative ATP synthesis activity. These processes were measured based on the dynamics of creatine phosphate (PCr) content. 2. Muscle oxygen stores were depleted using ischaemia without stimulation as indicated by PCr breakdown after 250 +/- 33 s (mean +/- S.D.; n = 5), which provided a measure of the basal metabolic rate (0.008 +/- 0.002 mM s-1, n = 5). 3. The PCr breakdown rate during twitch stimulation of the oxygen-depleted muscle was constant at 1 Hz at 0.15 +/- 0.03 mM PCr per second or per twitch (n = 8). A constant cost per twitch was found from 0.5 to 2 Hz stimulation (depletion of PCr per twitch = 0.15 mM per twitch). 4. No net anaerobic recovery of PCr was found during a 2 min post-stimulation ischaemia. 5. Upon restoration of blood flow, PCr recovery followed an exponential time course with a time constant of 63 +/- 14 s (n = 8). From these recovery rates, the capacity for oxidative phosphorylation was estimated to be 0.4 mM s-1. 6. This experimental approach defines a non-invasive and quantitative measure of human muscle ATPase rate and ATP synthetase rate.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.1993.sp019673

Separate measures of ATP utilization and recovery in human skeletal muscle.

In mammals, nicotinamide phosphoribosyltransferase (NAMPT) is responsible for the first and rate-limiting step in the conversion of nicotinamide to nicotinamide adenine dinucleotide (NAD+). NAD+ is...

Skeletal muscle NAMPT is induced by exercise in humans

Humans produce less muscle force (F) as they age. However, the relationship between decreased force and muscle cross-sectional area (CSA) in older humans is not well documented. We examined changes in F and CSA to determine the relative contributions of muscle atrophy and specific force (F/CSA) to declining force production in aging humans. The proportions of myosin heavy chain (MHC) isoforms were characterized to assess whether this was related to changes in specific force with age. We measured the peak force of isokinetic knee extension in 57 males and females aged 23–80 years, and used magnetic resonance imaging to determine the contractile area of the quadriceps muscle. Analysis of MHC isoforms taken from biopsies of the vastus lateralis muscle showed no relation to specific force. F, CSA, and F/CSA decreased with age. Smaller CSA accounted for only about half of the 39% drop in force that occurred between ages 65–80 years. Specific force dropped about 1.5% per year in this age range, for a total decrease of 21%. Thus, quantitative changes in muscle (atrophy) are not sufficient to explain the strength loss associated with aging.

Kevin E. Conley

Papers

Oxidative capacity and ageing in human muscle

Mechanical stimuli regulate rapamycin-sensitive signalling by a phosphoinositide 3-kinase-, protein kinase B- and growth factor-independent mechanism.

Separate measures of ATP utilization and recovery in human skeletal muscle.

Skeletal muscle NAMPT is induced by exercise in humans

Decline in isokinetic force with age: muscle cross-sectional area and specific force.