Effects of age and resistance training on skeletal muscle: a review.

Key Words: Aging, Functional training and activities, Geriatrics, Muscle Performance, general, Neurophysiology/neuroanatomy.

An increasing number of older persons are thought to be living at or just above a threshold of physical capacity.[1] The occurrence of any illness may severely limit their functional capacity.[1] Thus, it is important to understand the effects of age on physical capacity and how extrinsic factors (eg, exercise) may alter an older person's physical capacity. This review examines age-related alterations in the neuromuscular system[2-22] and the effects of aged skeletal muscle resistance training on the neuromuscular system.[12,23-30] Findings from both animal and human studies are presented. To provide a basis for understanding the animal and human findings, differences in species' life spans, muscle fiber classification schemes, and exercise training protocols are reviewed. Clinical implications and future research concerning aged muscle resistance training are discussed.

Effect of Age Age on the Nouromuscular System

Decreases in skeletal muscle mass in aged organisms have frequently been documented.[9,31-33] For example, using ultrasonic imaging techniques, the cross-sectional areas of the gastrocnemius and soleus muscles of men and women 82 to 100 years of age were found to be less than those of men and women younger than 82 years of age.[9] In the older individuals, however, the declines in the cross-sectional areas of the gastrocnemius and soleus muscles were found to be less than the reductions in the amounts of torque generated by the muscles.[9] This discrepancy may be due, in part, to increases in fat and connective tissue in older muscles. An increase in fat infiltration in lean tissue of legs of sedentary older men has been reported.[34] in rats, age-related increases in endomysial[35] and perimysial[36] connective tissue have been found. Other alterations in the neuromuscular system may also contribute to the decline in older muscle force-generating capacity.

In this section, alterations in the neuromuscular system that may account for the decline in an older muscle's force-generating capacity will be reviewed. The effects of age on motor unit size, number, and structure; skeletal muscle cross-sectional area and number; and skeletal muscle anaerobic and aerobic metabolism in rats and humans are discussed. Overviews of the species and muscle fiber classification schemes often used in studies investigating the effects of age on the neuromuscular system are also presented.

Experimental Models and Designs

Species studied. The effects of age on the neuromuscular system have been studied primarily in rodents and humans. The laboratory rat is an often-used rodent model in investigations of the effects of age on the neuromuscular system because rats have a relatively short life span.[37] In addition, maintenance costs for rats are comparatively low, permitting production and maintenance of large colonies of animals for study.[37]

A question that arises is, "How old is an old rat?" In many studies, the "old" experimental group has been composed of rats that are 18 to 28 months of age.[2,3,12,16,21,38] Some strains (eg, Fischer 344 Brown Norway F1 hybrid), however, have been reported to survive approximately 40 months (unpublished information, National Institute on Aging). In addition, gender can affect the survival rate. For example, the 50% survival rate (age at which 50% of the colony has died) of the Fischer 344 Norway Brown F1 hybrid females is 190 weeks compared with 140 weeks for the males (unpublished information, National Institute on Aging). Thus, to define a rat as "old" requires knowledge of the strain survival curve for the gender studied.[37,41]

Housing conditions of a rat colony will also affect general health and longevity of rats.[37] Colonies are housed either under barrier (pathogen-free) or nonbarrier conditions. There is an increased incidence of infectious diseases in rats raised in nonbarrier conditions as compared with those raised in barrier conditions.[37] It is difficult, therefore, to determine whether decreases in physical capacity with age in nonbarrier-housed colonies are due to the aging process or to the increased incidence of diseases. As an example, rats raised in nonbarrier conditions are more prone to respiratory infections,[37] which may influence the oxidative capacity of skeletal muscles independent of the effects of age.

In humans, the effects of age on different physiological systems have been found to vary among systems and individuals.[14,42-6] Skeletal muscle can be influenced by many factors, including heredity, nutrition, and physical activity.[14,31,47] In experimental studies, these factors may be difficult to control. Therefore, when reporting findings of effects of age on the human neuromuscular system, detailed descriptions of the subjects (eg, chronological age, lifestyle, health and nutritional status, physical activity level) should be provided in order to aid in the interpretation of the results.

Finally, changes in skeletal muscle occur over the life span of a species.48 Thus, different age groups (young, adult, and old) of a species should be studied when investigating the effects of age on the neuromuscular system. Caution should also be used when comparing the results of studies using different age groups of the same species.

Skeletal muscle fiber composition. In many studies investigating the age-related changes in the neuromuscular system, muscles are classified based on their fiber type composition. In this review, fiber-typing nomenclature from the original articles will be used when skeletal muscles are referred to by their fiber composition.

Based on color, skeletal muscles are classified as either "red" or "white." "Red" muscles have a high capillary density, giving them a reddish appearance. "Red" muscles are considered to have a high capacity for aerobic metabolism. In contrast, "white" muscles have a low capillary density, giving them a pale appearance. "White" muscles are considered to have a high capacity for anaerobic metabolism. This classification scheme does not characterize a muscle's contractile properties.

Skeletal muscles are classified based on their contractile characteristics by determining the type of myosin adenosine triphosphatase (ATPase) in the muscles' fibers.[49] A histochemical reaction for myosin ATPase is often used to distinguish two types of muscle fibers: slow and fast.[49]

Peter et also attempted to utilize both contractile and metabolic properties of a muscle to characterize its composition. A muscle is classified as slow oxidative (SO), fast oxidative glycolytic (FOG), or fast glycolytic (FG) based on the muscle fibers' histochemical reaction for myosin ATPase and their glycolytic and oxidative enzyme activity levels.[50] Slow oxidative muscles are considered slow-twitch, with moderate oxidative capacity and low glycolytic capacity. Fast oxidative glycolytic muscles are considered fast-twitch, with high oxidative capacity and moderate to high glycolytic capacity. Fast glycolytic muscles are considered fast-twitch, with high glycolytic capacity and low oxidative capacity.[50]

The classification scheme of Peter et al,[50] however, has several limitations. The classification scheme was developed by selecting guinea pig and rabbit limb muscles composed predominantly or exclusively of one type of fiber and then studying the metabolic properties of these muscles.[50] In contrast, many muscles in a variety of species are composed of a variety of fiber types. In addition, since the development of the classification scheme of Peter et al,[50] incompatibility between the myosin-based fiber type classification system and classifications based on metabolic enzyme activity levels has been reported.[51-53] For example, large variations in mitochondrial succinate dehydrogenase (SDH) enzyme activity exist in muscle fibers stained for myosin ATPase.[51-53] Yet, the histochemical reaction for myosin ATPase is often used to divide muscles into slow and fast categories, and then fast muscles are further subtyped into SO, FOG, and FG subcategories based on the intensity of the SDH reaction end-product.

In another classification scheme, that of Brooke and Kaiser,[54] fibers are stained for myosin ATPase following acid or alkaline preincubations. Classification using the Brooke and Kaiser method54 yields the following fiber categories: type I (slow-twitch) and three subcategories of type II (fast-twitch), type IIa, type IIb, and type IIc. Metabolically, type I fibers are often correlated with SO fibers, type IIa fibers with FOG fibers, and type IIb fibers with FG fibers. Type IIc fibers are rarely identified in normal, mature human muscles.[54] In myosin ATPase-stained fibers in a variety of

species, however, the activity levels of oxidative and glycolytic enzymes have been found to vary within a specific fiber type category.[55-57]

It is difficult, therefore, to draw conclusions about a muscle's contractile properties based solely on its metabolic properties or about a muscle's metabolic properties based solely on its contractile properties. One reason for the lack of correlation between contractile and metabolic classifications is that metabolic features are very mutable and reflect the type, intensity, and duration of activity of a given fiber in a given muscle.[58]

Effect of Age on the Motor Unit

Campbell et al[5], found that the size of human motor units increased with increasing age. The mean amplitude of extensor digitorum brevis muscle single motor unit action potentials recorded from humans 60 to 96 years of age (47.6-43.2 [mu]V) was greater than those recorded from humans 3 to 58 years of age (29.9[+ or -]25.5 [mu]V).[5] The increase in the size of aged motor units may be due to surviving axons adopting denervated muscle fibers (formation of larger or giant motor units)[5,6] or to hypertrophy of surviving muscle fibers. If larger or giant motor units do occur in older individuals, the degree of control older individuals have over their muscles may decrease.

Loss of recruitment of some of the remaining giant motor units or firing of giant motor units at suboptimal frequencies during a maximal voluntary contraction (MVC) could produce a decline in muscle force-generating capacity in older persons. Vandervoort and McComas[6] assessed whether older individuals activated their ankle plantar-flexor and dorsi-flexor muscles optimally. The amounts of torque produced during an MVC and during application of supramaximal electrical stimulations superimposed on an MVC were recorded. The amount of torque generated during an MVC was greater in men than in women, regardless of age. The amount of torque generated during an MVC declined after 60 years of age in both men and women. During an MVC, electrical stimulation of the motoneurons produced no additional torque in either the plantar-flexor or dorsiflexor muscles in the majority of men and women, 20 to 100 years of age.[6] Thus, older individuals appear to be able to use descending motor pathways to optimally activate ankle plantar-flexor and dorsiflexor muscles. Further investigation is needed to determine whether the electrophysiological findings in the ankle plantar-flexor and dorsiflexor muscles[6] are indicative of what occurs in other muscles.

A decline in the number of motor units has been found in older humans.[5,7,8] Between the ages of 3 and 58 years, the mean number of human extensor digitorum brevis muscle motor units was 197-58 units.[5] After 60 years of age, the number of motor units decreased to fewer than 100.[5] Between the ages of 60 and 96 years, the number of motor units decreased with increasing age.[5] In the biceps brachii muscle, individuals over 60 years of age had approximately half the number of motor units as compared with individuals under 60 years of age.[7] After the age of 60 years, motoneuron counts in the lumbosacral portion of human spinal cords decreased by 50% as compared with prior to 60 years of age.[6] Thus, a factor contributing to the decline in aged human muscle force-generating capacity appears to be an age-related reduction in the number of motor units. This decline in the number of motor units, however, appears to begin only after the age of 60 years.

There is evidence that the conduction velocities of surviving motoneurons slow with age.[4,5] The conduction velocities of the fastest-conducting nerve fibers innervating the extensor digitorum brevis muscle fibers decreased in 60- to 96-year-olds as compared with 3- to 58-year-olds.[5] In addition, marked slowing of conduction velocities in the distal regions of some axons in 24- to 36-month-old rats suggests that axons undergo segmental demyelination.[4] This slowing may be indicative of an age-related dysfunction of Schwann cells. The surviving slower-conducting motoneurons may innervate slower-twitch muscle fibers. Because a slower-twitch fiber generates lower force per unit area of the fiber, a predominance of slower-conducting motor units in older persons could contribute to the decreases observed in force generating capacity.

Effect of Age on Skeletal Muscle Morphology

In rats[2,10,13,16,47] and humans,[12,14,15] decreased muscle mass has been attributed to decreases in the number[2,13,15,47] and area[10,12-15] of the muscle fibers. In 24-month-old rat soleus muscles, atrophy and loss of motoneurons were found.[2] in male and female Wistar rats, tibialis anterior muscle weight decreased over 50% between 12 and 24 months of age.[13] In the tibialis anterior muscles of 24-month-old rats, the area of "white" fibers and the number of "red" fibers decreased compared with the muscles of 12-month-old rats.[13] Similar findings were observed in psoas major muscles from the 24-month-old male Wistar rats.[13]

Fibers in both the soleus and extensor digitorum longus muscles from 30-month-old female albino rats decreased 25% to 30% as compared with fibers of muscles from 3- to 4-month-old rats. In both muscles, there were decreases in the percentages of FOG fibers and increases in the percentages of SO fibers.[11] There were no differences in the percentages of type I, IIa, or IIb fibers in extensor digitorum longus muscles from barrier-reared Fischer 344 male rats ranging in age from 3 to 30 months.[47] In contrast, the soleus and diaphragm muscles from the 30-month-old Fischer 344 rats had a higher percentage of type I fibers and a lower percentage of type IIa fibers than did muscles from the younger rats.[47] The total number of fibers per cross-sectional area of muscle, however, did not change With age in either the extensor digitorum longus or soleus muscles of the Fischer 344 rats.[47]

Brown found no change in the total number of fibers in both soleus and extensor digitorum longus muscles in 24-month-old Wistar rats as compared with 12-month-old rats.[16] Fiber atrophy, however, was noted in the muscles after 12 months of age.[16] Type 11 fiber atrophy has also been found in soleus and extensor digitorum longus muscles of 28- to 36-month-old male Wistar rats as compared with muscles in younger Wistar rats.[10]

In biopsy samples from vastus lateralis muscles of sedentary men, 20 to 65 years of age, the percentage of type I fibers in the muscles increased with increasing age.[12] There were also decreases in both type I and II fiber areas in the vastus lateralis muscle biopsy samples from the older men as compared with fiber areas in biopsy samples from the younger men.[12] The decrease in fiber area in the older men was greatest in type II fibers.[12] In men and women up to 81 years of age, no gender differences in the percentages of type I and type II fibers were found in vastus lateralis or biceps brachii muscle biopsy samples for any of the age groups.[14] There was, however, a decline in type II fiber area, especially type IIb fiber area, in the vastus lateralis muscle biopsy samples from the oldest individuals (78-81 years of age) as compared with fiber areas in muscle samples from younger individuals.[14] The biceps brachii muscle of the 78- to 81-year-old individuals did not show any decline in fiber area with age as compared with fiber areas in muscle samples from younger individuals.[14] In autopsied whole vastus lateralis muscles from men 19 to 37 and 70 to 73 years of age, there were no differences between the age groups in the percentages of type I and type II fibers or in the type I and II fiber areas.15 Both the size of the muscle and the total number of fibers in the vastus lateralis muscles, however, decreased with age.[15]

The ability of aged rat and human muscles to generate force would decrease as a result of an age-related atrophy or loss of muscle fibers. An age-related atrophy or loss of muscle fibers could also result in an eventual decrease in the size of aging motor units (eg, the number of fibers innervated by an axon). The decrease in the size of motor units may be due to a decline in the capacity of aging motoneurons to sprout nerve terminals. Denervation of fibers within the muscle, and atrophy and eventual loss of the denervated muscle fibers, would then occur. This hypothesis is supported by findings of reductions in the terminal branching of motoneurons and the length of the end-plates in the soleus muscles of 28-month-old female Wistar rats[3] and of retraction of the terminal boutons from the sarcolemma and destruction of the sarcolemma infoldings in 36-month-old rat soleus muscles.[4]

The conflicting findings regarding the effect of age on motor unit size (increased[5] versus decreased[2,10,12-15] may be due to differences in activity levels among muscle groups studied.

The amounts of atrophy that occur in old muscle fibers appear to be influenced by the amount and type of muscle activity the old muscle undergoes.[59]

In addition, in rats, the decreases in muscle fiber numbers and in type II or FOG fiber percentages do not appear to be consistent aging phenomena.[2,10,13,16,47] Differences are seen between muscles in the same strain of rats[47] and in the same muscles between strains.[11,47] Eddinger et al[47] proposed that fiber numbers are genetically determined. Thus, changes in fiber number and percentages with age may be genetically determined.[47]

The disparate findings regarding the effects of age on the area and percentages of fibers in vastus lateralis muscle biopsy samples[12,15] may be due to differences in the biopsy sites used in the studies. The sizes and percentages of fiber types vary in different parts of the muscle.[60] Thus, findings may vary among studies if different portions of the vastus lateralis muscle are sampled. Sampling from a single area of the vastus lateralis muscle may not give findings representative of the whole muscle. This could account, in part, for the divergent findings regarding the effects of age on human muscle morphology in vastus lateralis muscle biopsy samples[12,14] as compared with whole vastus lateralis muscles.[15]

Effect of Age on Skeletal Muscle Metabolism

Muscle metabolism is one of the factors that influence the length of time a maximal contraction or a series of repeated contractions can be maintained. The activity levels of enzymes catalyzing skeletal muscle anaerobic[10,14,21,40,60] and aerobic[10,14,20,21,40,60] metabolism and the concentrations of intramuscular substrates used during anaerobic metabolism[17-19,22,62] in aged rat[10,1-21,38-40] and human[14,22,62] muscles have been measured. Both the presence[10,17-22] and absence[14,3-40,61] of age-related declines in enzymatic activity levels[10,14,20,21,40,61] and intramuscular substrate concentrations[17-l9,22,38,39] have been reported.

Decreases in glycolytic,[10,21] [beta]-oxidation,[20,21] and citric acid cycle[10,20] enzyme activity levels have been found in older rat muscles having a high percentage of slow-twitch fibers. In contrast, rat muscles composed of a high percentage of fast-twitch fibers appear to decrease their glycolytic capacity but increase their oxidative capacity with age.[10,21] Bass et al[10] reported that activity levels of three glycolytic enzymes-triosephosphate dehydrogenase (TPDH), lactate dehydrogenase (LDH), and glycerol-3-phosphate dehydrogenase (GPDH)-were decreased in extensor digitorum longus ("fast") and soleus ("slow") muscles of 28- to 36-month-old untrained male Wistar rats as compared with the same muscles in 3-month-old untrained rats. Activity levels of malate dehydrogenase and citrate synthase (CS) (citric acid cycle enzymes) were only decreased in the soleus muscles of the older rats.[10]

The activity levels of LDH and hexokinase (HK) (glycolytic enzymes) and of 3 hydroxyaxyl CoA dehydrogenase (HAD) (a [beta]-oxidation enzyme) decreased in the extensor digitorum longus and soleus muscles from 24-month-old untrained male Wistar rats as compared with 3-month-old rats of the same strain.[21] Although the activity level of CS decreased in the 24-month-old rats' soleus muscles, the CS activity level increased in the rats' extensor digitorum longus muscles.[21] The activity levels of acyl-CoA dehydrogenase and HAD ([beta]oxidation enzymes) and CS, NAD-isocitrate dehydrogenase, and 2-oxoglutarate dehydrogenase (citric acid cycle enzymes) were decreased in 24-month-old untrained male Wistar rats' soleus muscles ("red oxidative") as compared with the soleus muscles of 6-month-old untrained rats.[20]

Other investigators have reported no age-related declines in glycolyic,[14,40,60] [beta]-oxidation,[14,40,61] and citric acid cycle[14,40], enzyme activity levels in rat[40] and human[14,61] muscles. In epitrochlearis muscle (composed primarily of FG fibers) from 9- and 24-month-old barrier-raised male Long-Evans rats, no differences in HK, phosphorvlase, and pyruvate kinase glycolytic enzymes); HAD (a [beta]-oxidation enzyme); and CS and succinatc dehydrogenase (citric acid cycle enzymes) activity levels were found.[40] In 56 sedentary men, 22 to 65 years of age, no differences in phosphofructokinase, LDH, HAD, and CS enzyme activity levels in vastus lateralis muscle biopsy samples from younger and older individuals were found.[61] In addition, no declines in hexokinase, LDH, HAD, and CS enzyme activity levels were found in biopsy samples of vastus lateralis and biceps brachii muscles from 80-year-old men and women as compared with younger men and women.[14] In this study,[14] no differences in enzyme activity levels between sexes were found except for higher HK activity levels in vastus lateralis and biceps brachii muscle biopsy samples from women as compared with men.

Conflicting findings regarding the effect of age on intramuscular anaerobic substrate contents have also been reported.[17-19,38,39] Ermimi[17] and Ermimi and Verzar[18] found that the concentrations of phosphocreatine (PC) were reduced in the rectus femoris and gluteus maximus ("white") muscles and the piriformis, vastus intermedius, and gluteus maximus centralis ("red") muscles from 33- to 37-month-old untrained Wistar rats as compared with the same muscles of rats younger than 33 months of age. in the "red" muscles, adenosine triphosphate (ATP) and adenosine diphosphate (ADP) concentrations were also significantly reduced.[17,18] In addition, the intracellular glycogen content decreased by 50% in the "white" and "red" muscles of the old rats.[19] In vastus lateralis muscle biopsy samples from healthy men and women, 52 to 79 years of age, intracellular concentrations of ATP, ADP, adenosine monophosphate (AMP), and PC decreased only 5% as compared with contents in muscle biopsy samples from men and women approximately 40 years younger.[22] No differences in resting concentrations of ATP, PC, and glycogen were found in 10- and 24-month-old untrained barrier-raised male Fischer 344 rats' "white" gastrocnemius (FG fibers), "red" gastrocnemius (FOG and SO fibers), plantaris (FOG and SO fibers), and soleus (SO fibers) muscles[38] and in 9- and 28-month-old untrained barrier-raised male Long-Evans rats' soleus muscles.[39]

In summary, it appears that there is little decline in anaerobic and aerobic metabolism in "active, community-living" 80-year-old individuals when compared with younger individuals.[14,22] Caution should be exercised in applying this conclusion to all older persons, however, until "active" and "community-living" are better defined.

The findings regarding the effect of age on anaerobic and aerobic metabolism in rats' muscles appear to be conflicting. The disparate metabolic findings in old rats' muscles can be attributed, in part, to differences in the ages of the rats investigated. Decreased enzyme activity levels and intramuscular substrate concentrations were often reported in Wistar rats older than 30 months of age.[10,17-19] Wistar rats rarely survive to 40 months of age. Thus, rats 30 months and older could be considered to be "very old."[18] The Wistar rats were also raised under nonbarrier conditions[10,17-21] and thus may have had respiratory diseases that might have affected their aerobic metabolism. When no decline in enzyme activity levels[40] and intramuscular substrate concentrations[38,39] were reported, rats younger than 28 months of age were investigated. In these studies,[38-40] the rats were also raised under barrier conditions. Thus, these animals[30] would be less likely to experience respiratory infections that might affect the oxidative capacity of muscle, independent of age. In addition, in rats older than 30 months, the decline in metabolism may be due to a decrease in physical activity rather than age. The activity of the 33- to 37-month-old rats, for example, was described as "slow," whereas those rats less than 33 months of age were described as "lively and active."[18]

Effects of Resistance Training on Aged Skeletal Muscle

Exercise training is thought to attenuate the age-related decline in human physical capacity.[1] In an attempt to increase the force-generating capacity of aged muscles and decrease the effects of age on the neuromuscular system, resistance training (eg, strength training) of aged human muscle has been performed, with varying amounts of success reported.[12,23-30] In this section, an overview of exercise training protocols will be presented. The effects of resistance training on aged human muscle force-generating capacity and on aged rat and human neuromuscular systems are then examined.

Exercise Training Protocols

To obtain a training effect in muscle, an exercise overload must be applied.[62] Adaptations of muscles to training are related to the type, intensity, and duration of the training and to the type of muscle being exercised. The extent of training is, at least in part, a function of the pretraining state of the muscles being used in the exercise.[62] Exercise training protocols should be described by the type, intensity, and amount of exercise performed by the subjects.[62]

Types of exercises used to increase the physical capacity of older persons are resistance and cardiovascular endurance training.[1] The intensity of exercise can be expressed in a number of different ways. In resistance training, repetition maximum (RM), which describes the maximum amount of weight that can be moved through a joint's full range of motion a specified number of times, is often used to describe the intensity of exercise.[63] Also, force, torque, or power is measured during an MVC, and the intensity of resistance training is then established using a percentage of the maximum force, torque, or power measurement.[62] During cardiovascular endurance training, the intensity of exercise is expressed as a percentage of maximum aerobic capacity.[1,62] Maximum aerobic capacity is the maximum rate at which oxygen can be used by the muscles. It does not describe the anaerobic capacity of an individual and therefore should not be used when describing activities that require little oxygen (eg, high-intensity resistance training). The amount of exercise performed is expressed as the number of minutes per day times days per week times total weeks the exercise was performed.

Effect of Resistance Training on Aged Muscle Force-Generating Capacity

The effects of isometric and isotonic resistance training on muscle force-generating capacity in healthy, community-living older persons have been investigated.[23-25] Licmohn[23] investigated the effects of age and isometric resistance training on the force-generating capacity of human upper- and lower-extremity muscles. Twenty-seven healthy men, 41 to 80 years of age, participated in one of two training programs. Each training group performed 15 minutes of exercise, 3 days a week, for 6 weeks. One training group performed three isometric contractions with four different muscle groups (forearm flexors, forearm extensors, knee flexors, and knee extensors). The intensities of isometric contractions were not specified. The second training group performed balance, flexibility, and coordination exercises, avoiding "overload" to the knee and forearm flexor and extensor muscles. The term "overload" was not operationally defined.[23] The balance, flexibility, and coordination exercises were not described.[23]

Prior to training, isometric forces generated by the muscle groups were lower in the older (61-80 years) age groups as compared with the younger (41-60 years) age groups.[23] Following isometric resistance training, forces generated by the right and left elbow extensors and left elbow flexors in the 41- to 50-year-old age group and the right knee flexors and right elbow extensors in the 51- to 60-year-old age group were increased as compared with pretraining forces.[23] In the 61- to 80-year-old age group, however, there were no increases in forces generated by any of the muscle groups following isometric resistance training.[23] The maximum isometric forces generated by the different muscle groups in the different age groups following balance, flexibility, and coordination training were less than those generated by the age-matched isometric resistance trained groups.[23] The lower isometric forces generated following balance, flexibility, and coordination training as compared with isometric resistance training may be due to a lack of training and testing specificity and to a lack of any overload being applied to the muscles in the balance, flexibility, and coordination training group.

In contrast to Liemohn's findings,[23] Kauffman[24] found that the isometric force generated by a small distal upper-extremity muscle abductor digiti minimi) was unchanged with age and that high-intensity isometric resistance training increased the force-generating capacity of the muscle in both younger and older humans. Ten healthy women, 20 to 26 years of age, and 10 healthy women, 65 to 73 years of age, performed two sets of 10 maximal isometric contractions of the left abductor minimi muscle, three times a week for 6 weeks. Prior to isometric resistance training, there was no significant difference between the younger and older women in the amount of isometric force generated by their abductor digiti minimi muscles. At the end of 6 weeks of training, the average gains in the amount of isometric force generated by abductor digiti minimi muscle of younger and older women were similar (819 and 607 g).[24]

The effects of high-intensity isometric and isotonic resistance training on the force-generating capacity of aged human muscles have been compared by Perkins and Kaiser.[25] Five healthy men and 15 healthy women, 62 to 84 years of age ([bar] X=73.6), performed either isometric or isotonic resistance exercise of the plantar flexors of the ankle, the extensors of the knee, and the extensors of the hip, three times a week for 6 weeks. The isometric exercise program consisted of holding the maximum resistance load for each muscle group for 6 seconds, followed by holding one half of the maximum resistance load for another 6 seconds. During a training session, each isometric resistance load was held three times per muscle group. The isotonic resistance training protocol consisted of performing the 10 RM for the muscle group followed by performance of one half of the muscle group's 10 RM each exercise session. New isometric and isotonic maximum resistance training loads were established weekly. Following 6 weeks of isometric and isotonic resistance training, the mean percentage increases in the amounts of muscle force generated were 46% (isometric) and 57% (isotonic).[25]

In three studies,[23-25] the differences in the force-generating response of aged muscle to isometric resistance training were most likely due to differences in exercise training intensities. In younger individuals, the largest gains in force-generating capacity occur when high-resistance loads are applied to muscles.[62] Similar findings are seen in older muscles.[24,25] The largest gains in force-generating capacity were found when older muscle groups were resistance trained using maximum loads and these loads were adjusted on a weekly basis to maintain that muscle overloading throughout the training period. Specificity of training and testing principles were also adhered to in these studies.[24,25] In addition, it appears that both isometric and isotonic resistance training are capable of increasing healthy aged skeletal muscle force-generating capacity to an equivalent degree if both types of training use heavy resistance.

In contrast, in Liemohm's[23] Study, in which no increase in old muscle force-generating capacity was found, isometric training at unspecified intensities was performed. Thus, it is not known whether these muscles were significantly overloaded throughout the training period. In addition, the contrasting findings of Liemohn's[23] and Kauffman's[24] studies reinforce the idea that the effects of age and resistance training may not be the same in different muscles. The activity levels of muscles over a life span may influence the muscles' responses to aging and training. Thus, caution must be used when generalizing results from one muscle to other muscles in the body.

There may be a reluctance on the part of some physical therapists to use high-intensity resistance training for older persons, due, in part, to the presence of multiple chronic medical conditions in these individuals or to concerns regarding the ability of old muscles to tolerate MVCs. Recently, the effects of high-intensity isotonic resistance training on muscle force-generating capacity have been investigated in 10 "frail" older persons (4 men, 6 women; 90 [+ or -] 1 years of age) who were institutionalized.[26] The individuals were ambulatory, were not acutely ill or diagnosed with unstable cardiovascular disease or uncontrolled chronic conditions, and were able to follow simple commands. No additional definition of frailty was provided. The individuals trained for 8 weeks, three times a week, performing three sets of eight repetitions. The subjects trained at 50% of their one RM during the first week of training and then at 80% of their one RM during weeks 2 through 8 of training. Regional body composition, using computed tomography (CT) scans of the thigh, were obtained prior to and within 1 week of the completion of training. Functional mobility was assessed using the chairstand maneuver and gait observations at the beginning and end of training.[26]

Following training, the amount of maximum muscle force generated by the older subjects significantly increased 174% [+ or -] 31%).[26] The midthigh muscle area, based on CT scan measurements, increased 9.0% [+ or -] 4.5% following training.[26] Habitual (eg, preferred) gait speed did not change significantly with training, but tandem (not defined) gait speed significantly increased (48%) following training.[26] Two subjects, who ambulated with the assistance of a cane prior to training, no longer used the cane following training.[26] One of three subjects who could not rise from a chair without using their arms could do so following training.[26] No cardiovascular complications occurred during the training sessions in any of the subjects.[26] One subject, however, had to withdraw following 4 weeks of training because of complications related to a previously repaired hernia.[26] These preliminary findings in a very small sample[26] suggest that high-intensity isotonic resistance training can produce an increase in muscle force-generating capacity in very old individuals without negative effects. In addition, the increase in muscle force-generating capacity in these very old persons may be correlated with an increase in functional performance. This hypothesis, however, needs to be confirmed in investigations of larger samples of older persons, using reliable and valid functional assessment tests.

Findings of Brown[27] Suggest that there is little damage to older muscle following manual resistance training. Female Sprague-Dawley rats, 21 to 30 months of age (50% longevity of females of this strain was 30 months), performed three sets of 10 repetitions of manually resisted chin-ups twice a day for 3 months.[27] No indicators of damage (eg, large numbers of macrophages, central nuclei, loss of striations) in trained palmaris longus muscles were found in any of the aged groups.[27] A definitive conclusion that an MVC does not cause damage to older muscle, however, cannot be drawn from Brown's study.[27] It was not conclusively shown that MVCs of the palmaris longus muscles were being performed during the manually resisted chin-ups. The amount of overload being applied to the palmaris longus muscle was also not quantified.[27]

Effects of Aged Muscle Resistance Training on Motorneurons

Moritani and deVries[28] have attributed the increase in aged muscle force-generating capacity following resistance training to changes in neural activity. Male subjects, 18 to 26 years of age and 67 to 72 years of age, performed 10 repetitions of elbow flexion at 66% of the muscle's 10 RM. The exercises were performed twice a day, three times a week, for 8 weeks. Every 2 weeks, the maximal isometric forces generated by the elbow flexors, the electrical activity of the biceps brachii muscles, and the cross-sectional areas of the elbow flexor muscles were measured.[28]

Prior to training, there were no differences between the younger and older men in the maximal isometric forces generated by the muscles, the electrical activity of the muscles, and the cross-sectional areas of the muscles.[28] Following training, the maximal isometric force generated by the trained elbow flexors of the younger and older men increased 30% and 20%.[28] In the younger men, the electrical activity of the muscles and the cross-sectional areas of the muscles both increased approximately 10%.[28] In the older men, the electrical activity of the muscles and the cross-sectional areas of the muscles increased approximately 20% and 2%.[28]

Moritani and deVries[28] concluded that during the first 4 weeks of training, the increase in tension-generating capacity in younger muscles was due to neural factors, as evidenced by an increase in the electrical activity of the muscles with no change in the cross-sectional areas of the muscles during this time. During the final 4 weeks of training, the increased force-generating capacity of the younger muscles appeared to be due to hypertrophy, as evidenced by an increase in the cross-sectional areas of the muscles with little change in the electrical activity of the muscles during this period. In contrast, the authors concluded that the increase in force-generating capacity in older muscles during the 8 weeks of resistance training was due mainly to neural factors, as evidenced by findings of a greater increase in the electrical activity of the muscles without any increase in the cross-sectional areas of the muscles following training.[28] Neural factors, as defined by Moritani and deVries,[28] were either an increase in facilitation or disinhibition within the central nervous system.

It appears, based on Moritani and deVries' findings,[28], that older persons increase their muscle force-generating capacity following moderate-intensity (66% of 10 RM) resistance training because of activation of neuromotor patterns that enable the older individual to coordinate his or her muscles more effectively to exert a greater force (eg, motor learning). One might also conclude from Moritani and deVries' findings[28] that a muscle loses its ability to hypertrophy in response to resistance training as it ages. The lack of hypertrophy in older muscles, however, may be due to an underestimation on the part of the investigators of the amount of resistance needed to be applied to the older muscles to produce hypertrophy. Moritani and deVries[28] also used anthropometric methods (skinfold and girth measurements) to estimate muscle mass. Anthropometric methods do not provide an accurate assessment of hypertrophy[31]; thus, Moritani and deVries'[28] conclusions may be inaccurate.

Moritani and deVries' findings[28] are difficult to generalize to other muscles and individuals because these investigators did not normalize the electrical activity of the muscles. When measuring electrical activity of muscles during isometric contractions, the variables affecting the signal (eg, time, force, body composition) must be normalized with respect to their maximal measurable values for the particular experimental procedure.[64]

Chronic exercise appears to increase terminal sprouting in aged motoneurons.[65] in soleus muscles from 26-month-old female Fischer 344 rats that performed 5 months of treadmill exercise, 30 minutes a day, 5 days a week, an increase in terminal sprouting of the soleus motoneurons was found as compared with 26-month-old untrained rats.[65] In the gastrocnemius muscle, there was no difference between the 26-month-old trained and untrained rats in the amount of motoneuron terminal sprouting.[65] This finding does not necessarily mean that aged slow-twitch motor units are more capable of initiating terminal sprouting in response to exercise than aged fast-twitch motor units. Rather, the results may be due to the exercise protocol used in this study.[65] During endurance training, a predominance of slow-twitch motor units are recruited. Thus, the effects of chronic resistance exercise on motor unit terminal sprouting in older individuals needs to be investigated. Because axon withdrawal has been suggested as a possible cause of fiber atrophy in older muscles,[6] an increase in terminal sprouting and end-plate growth in response to chronic exercise might reduce the amount of fiber atrophy and fiber loss seen in older muscle.

Effects of Resistance Training on Aged Skeletal Muscle Morphology

Following high-intensity resistance training, increases in maximum force-generating capacity have been associated with muscle hypertrophy in both healthy elderly men[29] and women.[30] Twelve men, 60 to 72 years of age, participated 3 days a week for 12 weeks in high-intensity isokinetic resistance training.[29] During each training session, subjects performed three sets of eight repetitions of knee flexion and extension (covering a range of motion of 90[degrees]) at 80% of the muscles' one RM. Prior to and following the 12 weeks of training, peak torques of the extensor and flexor muscles were measured, and needle biopsies of the left vastus lateralis muscles and CT scans of the thighs were performed. Biopsy samples were stained for myofibrillar ATPase, and muscle fibers were classified as either type I or II.[29]

Following 12 weeks of training, knee extensor and flexor muscle peak torques, as measured by the isokinetic dynamometer, increased 10% and 18% at 60[degrees]/s and 17% and 15% at 240[degrees]/s.[29] Peak torques of the knee extensors and flexors, as measured by the one-RM test, increased 107% and 227%.[29] The area of the quadriceps femoris muscle increased 9%.[29] Cross-sectional areas of type I and type II fibers increased 34% and 28%.[29]

In another study,[30] 13 women, 64 to 86 years of age, participated in 12 weeks of moderate- to high-intensity isotonic resistance training of the quadriceps femoris, hamstring, gluteus medius, adductor magnus, iliopsoas, and gluteus maximus muscles. Subjects in the training group exercised at 65% of one RM during the first 5 weeks, 70% for 4 weeks, and 75% for 3 additional weeks. Training sessions were conducted 3 days a week, and three sets of six repetitions of each exercise were performed during each training session. Six women, 64 to 86 years of age, served as control subjects and received no active intervention. Measurements of maximum force-generating capacity for each muscle and needle biopsies were taken from the vastus lateralis muscles at the initiation and conclusion of the study. Fibers were stained for myofibrillar ATPase to differentiate type I and II fibers.[30]

Maximum force-generating capacity increased 28% to 115% in all muscle groups following training.[30] type II cross-sectional fiber area in the vastus lateralis muscle biopsy samples increased 20% following resistance training.[30] No significant increases in the maximum force-generating capacity and type II cross-sectional area in control subjects and in type I cross-sectional area in either group were found.[30]

The 20% increase in the type II fiber cross-sectional area in healthy older women[30] is less than the 45% increase in type II fiber cross-sectional area observed in healthy younger women who performed 6 to 8 repetitions per muscle group of high-intensity resistance training at 80% to 85% of one RM for 20 weeks.[66] The lower type II fiber hypertrophy in older muscles as compared with younger muscles following high-resistance training may be due to a difference in training regimens (moderate resistance training[30] versus heavy resistance training,[66] 12-week training period[30] versus 20-week training period[66]) or an age-related constraint on hypertrophy. To determine whether there is an age-related constraint on hypertrophy during resistance training, both younger and older subjects need to perform the same training protocols. There also may be a gender difference in the hypertrophy response of older muscle to resistance training. Following resistance training, the areas of both type I and type II fibers increased in the vastus lateralis muscle biopsy samples.[29] In vastus lateralis muscle biopsy samples from the older women, however, only the area of type II fibers increased.[30] These differences need to be investigated further.

The finding that hypertrophy of older muscles can occur following high-intensity resistance exercise[12,29,30] appears to contradict the findings of Moritani and deVries,[28] who reported no significant muscle hypertrophy following moderate-intensity resistance training. Differences in measurement techniques may explain the disparity in the findings. Moritani and deVries[28] used anthropometric measurements to estimate muscle mass, a relatively crude measure. More recent studies[12,29,30] used more sensitive methods (histochemical techniques,[12,29,30] CT scans[29]) to examine whether muscle hypertrophy occurred in older subjects.

The magnitude of the increases in force-generating capacity and fiber cross-sectional area appears to be dependent on the intensity of resistance training. Low-resistance training appears to result in little improvement of aged muscle's maximum force-generating capacity but may reverse, in pall, aged muscle's atrophy.[12] Aerobic exercise was performed by 18 men, 20 to 65 years of age, twice a week for 15 weeks using a 10-station circuit-training program. At each station, 20 to 30 repetitions of exercise were performed using either body weight or light weights for resistance. Knee extensor muscle exercises were incorporated in every second station. No descriptions of the exercises at each station or a definition of the term "light weight" were given. Maximum force produced by the left knee extensor muscles was measured, and needle biopsy samples were taken from the left vastus lateralis muscle before and after training.[12]

Prior to training, the average amount of force produced at the different isokinetic angular velocities was less in the 56- to 65-year-old age group than in the 29- to 39-year-old age group.[12] The proportion of type I fibers was 19% greater in muscle samples obtained from the older age group as compared with the younger age group.[12] In the older age group, the cross-sectional areas of type I and II fibers were also 29% and 38% less compared with the younger age group.[12] Following training, type I and II fiber cross-sectional areas increased 38% and 52% in the older individuals, whereas the increases in the fibers' cross-sectional areas were insignificant in the younger individuals.[12] The proponions of fiber types and the force-generating capacity at the different angular velocities in the younger and older age groups were unchanged following training.[12] Thus, the magnitude of the increases in force-generating capacity and fiber cross-sectional area following heavy resistance training appears to be dependent on the amount of overload applied to older muscles.

In addition, only high-intensity resistance training, not high-intensity cardiovascular endurance training, causes hypertrophy and an increase in muscle force-generating capacity in older muscles.[59] Maximal isometric force production, muscle mass, fiber cross-sectional area, and contractile protein content of the vastus lateralis and biceps brachii muscles were investigated in younger sedentary men (28 [+ or -] 0.1 years of age) and older sedentary men (68 [+ or -] 0.5 years of age) and in older male swimmers 69-1.9 years of age), runners (70 [+ or -] 0.7 years of age), and resistance-trained subjects 68 [+ or -] 0.8 years of age).[59]

For the 12 to 17 years previous to the study, the trained older men participated three times a week in swimming 800-1,000 m each session); running (9-12 km); or three sets of 10 repetitions of weight lifting using the legs, torso, shoulders, and arms. Knee extension and elbow flexion maximal isometric force values in older sedentary men were 44% and 32% less than the values for younger sedentary men.[59 ]The cross-sectional areas of the vastus lateralis and biceps brachii muscles of the older sedentary men were 24% and 20% less compared with those of the younger sedentary men.[59] Mean fiber areas in both the vastus lateralis and biceps brachii muscles were 24% less in the older sedentary men compared with the younger sedentary men.[59]

Higher myosin heavy chain and myosin light chain type I contents were also found in the vastus lateralis and biceps brachii muscles of the older sedentary men as compared with the younger sedentary men.[59] The muscles of older resistance-trained men had maximal isometric forces, muscle mass, fiber cross-sectional areas, and myosin heavy and light chain contents that were nearly identical to those of younger sedentary men.59 In contrast, the isometric force values, muscle mass, fiber cross-sectional areas, and myosin heavy and light chain contents of muscles from older runners and swimmers were similar to those of the older sedentary men.[59]

The hypertrophy of older muscles in response to high-intensity resistance training may be due to an increase in muscle protein turnover. During heavy resistance strength training of older muscle, there may be an increase in muscle fiber breakdown, with a concomitant increase in contractile protein anabolism between the exercise sessions. Increased muscle protein turnover has been demonstrated in male subjects between the ages of 20 and 30 years.[67] An increased rate of 3-methylhistidine excretion in the urine, an index of actin and myosin catabolism, was found following 12 days of resistance training at 60% to 70% of one-RM values of upper- and lower-extremity muscles in these individuals.[67] Contractile protein catabolism and anabolism in older skeletal muscle following high-intensity resistance training needs to be investigated.

Although the area of fibers increased, the percentages of fiber types in older human muscle did not change following resistance training.[12,29,30] Changes in the percentages of fiber types, however, have been found in the muscles of both older rats[68] and younger humans[66] following resistance training. Klitgaard et al- compared the effects of 36 weeks of resistance training on soleus and plantaris muscle morphology in 29-month-old male Wistar rats. Following 36 weeks of resistance training, type I and type IIa fiber cross-sectional areas were larger in both soleus and plantaris muscles that were exercised as compared with untrained control muscles.[68] The proportion of type I fibers decreased in soleus muscles from 36-week resistance-trained rats as compared with untrained control rats.[68] In the deep part of plantaris muscles from 36-week resistance-trained rats, type IIb fiber proportions increased and type I fiber proportions decreased as compared with untrained control rats.[68] Previously, Klitgaard et al[69] reported no age-related decline in twitch and tetanic tension generation in the soleus and plantaris muscles of 29-month-old rats that were resistance trained for 36 weeks. A decrease in proportion of type IIb fibers and an increase in the proportion of type IIa fibers were found in vastus lateralis muscles from younger women who were resistance trained at 80% to 85% of one RM for 20 weeks.[66]

When changes in fiber type percentages were found in muscles of both older rats68 and younger women,[66] the length of training was of long duration (20 weeks or greater). The lack of change in the proportions of fibers in older human muscles[12,29,30] may be due to the fact that the training durations used (12 weeks and less) were not long enough to induce a change.

Effects of Resistance Training on Aged Muscle Membolism

The effect of resistance training on anaerobic and aerobic metabolism in 24- and 29-month-old male Wistar rats following 20 and 36 weeks of resistance training was investigated by Klitgaard et al.[68] The activity level of CS (an aerobic enzyme) in the soleus and plantaris muscles of 24- and 29-month-old resistance-trained rats was lower than in the muscles of 24- and 29-month-old untrained rats.[68] In the soleus muscles of 24- and 29-month-old untrained and resistance-trained rats, there were no differences in the activity levels of the anaerobic enzymes TPDH and LDH.[68] The TPDH and LDH activity levels were higher, however, in the plantaris muscles of the 24- and 29-month-old resistance-trained rats as compared with the 24- and 29-month-old untrained rats.[68] Rat plantaris muscle has a greater proportion of fast fibers than does rat soleus muscle.[68] Because of its fiber composition, the aged plantaris muscle may have been activated to a greater extent than the aged soleus muscle during resistance training. This proposed difference in aged muscle activation during resistance training may have contributed to the differences between aged muscles in the anaerobic enzyme activity level following resistance training.[68] In this same study,[68] ATP and PC concentrations were 24% and 17% higher in the lateral gastrocnemius muscles of 29-month-old rats following 36 weeks of resistance training as compared with the ATP and PC contents of the muscles of age-matched control rats.

The finding that resistance training increases the capacity of aged rat muscle to generate ATP anaerobically[68] is similar to findings in younger human muscles.[70] Increases in the resting concentrations of ATP, PC, and glycogen in mixed fiber biopsy samples of triceps brachii muscle from younger men have been reported following high-intensity resistance training.[70] Younger men who have undergone high-intensity resistance training also have higher levels of muscle and blood lactate and a greater depletion of muscle glycogen during a session of resistance exercise as compared with untrained men.[70] Currently, one can only hypothesize that the anaerobic capacity of older human muscle following high-intensity resistance training will be increased.

Recommendations for a Therapeutic Approach for Improving Force Generation in Older Muscle

The following recommendations are based on what is known to date about the effects of resistance training on older muscle. To illicit the greatest increase in force in older muscles, high-intensity resistance training is necessary.[26,29] The isotonic resistance protocol that produced the greatest increases in force-generating capacity and attenuated atrophy to the greatest extent in older human muscle was three sets of eight repetitions of exercise performed at an intensity of 80% of a muscle's one RM, 3 days a week for 12 weeks.[29] Isotonic resistance training of older muscle can be initiated at an intensity of 50% to 60% of the muscle's one RM for 1 week and then increased to 80% of the muscle's one RM for the remainder of the training period.[26] Throughout the isotonic training period, maximum training loads need to be reestablished on a regular basis. A 6-second maximum isometric contraction repeated five times a training session, three times a week, can increase a muscle's force-generating capacity and mass following joint immobilization. This isometric resistance training protocol may also produce similar effects in older muscles. During high-intensity resistance training, older persons should be continuously monitored for heart rate, blood pressure, and any signs or symptoms of distress. Older individuals should also be cautioned to avoid performing Valsalva maneuvers during the exercise period, as this maneuver may place strain on the individual's cardiovascular system.

Future Research

Although it has been demonstrated that resistance training increases the force-generating capacity of older muscles, additional investigations regarding the effects of resistance training on aged muscles are warranted. The effects of resistance training on older muscle need to be investigated in larger samples of human subjects and in human muscles other than the gastrocnemius and the biceps brachii. The sample sizes of the human studies performed to date have been small. It is unclear whether the results obtained for the gastrocnemius and biceps brachii muscles can be generalized to other muscles, which might have different structures and functions. Larger numbers of persons 70 years of age and older need to be studied. Longitudinal population studies, in addition to cross-sectional population studies, are also needed. In addition, investigations of how factors such as gender, race, culture, and nutrition influence the age-related muscle alterations and the responses of aged muscles to resistance training are needed. Studies have only investigated the effects of age on muscle morphology and metabolism in biopsy samples obtained from older persons of Caucasian descent.[12,14,26,29,61]

Recently, it has been reported that fiber type proportion and muscle metabolism are also influenced by race.[71] Whether the findings from older persons of Caucasian descent can be applied to older women or older persons of other races and cultures is not yet known. In younger adults, dietary carbohydrate intake influences the rate and amount of glycogen repletion following a session of maximal exercise.[72] What effect nutrition in combination with exercise has on older muscle performance needs to be examined. Resistance protocols have differed with respect to types of contraction studied, loads applied to the muscle, number of repetitions performed, and frequency of training. In many reports, the protocols are poorly described, making it difficult to apply the methodology in clinical practice. Thus, more systematic comparisons, utilizing a variety of different exercise approaches, are needed.

Although high-intensity training increases force-generating capacity, little is known about its effects on functional performance. Unless investigations are conducted in which different measures of functional performance are made prior to and following resistance training, the validity of this approach to improving the quality of life of older persons cannot be established. In order to establish effective resistance training programs that optimally improve the physical capacity of older persons, the effect of resistance training on the neuromuscular system and other physiological systems must continue to be investigated.

Conclusion

High-intensity resistance training appears to be the most effective protocol to date in counteracting the changes in skeletal muscle morphology and performance seen in many older persons. Systematic investigations, however, of the effects of age on the neuromuscular system and of the effects of resistance training on the neuromuscular system and the functional capacity of older persons are essential for the development of cost-effective interventions that improve the physical capacity of older persons.

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JF Hopp, PhD, PT, is Assistant Professor, Department of Physical Therapy, College of Associated Health Professions, and Section of Geriatric Medicine, Department of Medicine, College of Medicine, University of Illinois at Chicago, 1919 W Taylor St (M/C 898), Chicago, IL 60612 (USA).