Ceasing of muscle function with aging: is it the consequence of intrinsic muscle degeneration or a secondary effect of neuronal impairments?

Aging is associated with a significant decline in neuromuscular function leading to an eventual loss of independence and mobility of senescent people. Age-related sarcopenia, characterised by a reduction in muscle mass and strength, is considered one of the most striking features of aging at the level of the skeletal muscle. Morphological alterations in skeletal muscle can be considered as one of the consequences responsible for muscle weakness in the aged population. Beyond 60 years of age, human muscle undergoes a process of continuous denervation and reinnervation, due to an accelerating loss of motor units. It appears evident that phenotypic alterations in muscle depend on the motor drives provided by the nervous system. Because the peripheral nerves, the neuromuscular junction and motor neurons exhibit degenerative features during advanced age, sarcopenia does not seem to intrinsically develop, but is rather a secondary effect of impaired neuronal function. It is therefore recommended that elderly subjects undergo an exercise program that is aimed towards the improvement of coordinative skills and of muscle strength.     

Aging, physical activity, and hormones in women--a review

Women experience significant changes in endocrine function during aging. Decreasing levels of anabolic hormones may be associated with musculoskeletal atrophy and decrease in function that is observed in older women and, as a result, there has been an increase in the use of pharmacological hormone therapies. It is difficult to distinguish, however, between physiological changes that are truly age related and those that are associated with lifestyle factors such as physical activity participation. Some research has shown that circulating levels of anabolic hormones such as DHEA(S) and IGF-I in older women are related to physical activity, muscle function, and aerobic power. Exercise-intervention studies have generally shown that increasing age blunts the acute hormonal response to exercise, although this might be explained by a lower exercise intensity in older women. There have been relatively few studies that examine hormonal adaptations to exercise training. Physical activity might have an effect on hormone action as a result of changes in protein carriers and receptors, and future research needs to clarify the effect of age and exercise on these other components of the endocrine system. The value and safety of hormone supplements must be examined, especially when used in combination with an exercise program.     

Muscle weakness in the elderly: role of sarcopenia, dynapenia, and possibilities for rehabilitation

Aging is a multifactorial process leading to changes in skeletal muscle quantity and quality, which cause muscle weakness and disability in the aging population. This paper discusses the reasons for muscle weakness??and its biological and physiological mechanisms??in the elderly and describes the role of sarcopenia and dynapenia, and the possibilities to modify the age-associated decline in muscle function and decelerate the development of muscle weakness and disability. Resistance and endurance training are effective measures of exercise therapy in the elderly, which improve muscle metabolism and thereby muscle function and life quality.     

Sarcopenia--a critical perspective

Aging is associated with a progressive decline in skeletal muscle mass and function (sarocopenia). Despite several years of research, controversy exists regarding the manifestations and causes of sarcopenia. In the former respect, whereas a preferential loss of so-called "fast-twitch" muscle fibers occurs in rat models of aging, this appears unlikely in human skeletal muscle. In the latter respect, whereas a decline in physical activity with aging contributes to whole-muscle atrophy, it cannot explain the marked heterogeneity in muscle fiber size seen in aged muscles. Similarly, systemic alterations, such as reduced blood levels of anabolic hormones and nutritional deficits, although involved in modulating the degree of whole-muscle atrophy, cannot explain the observation that only some fibers atrophy and die while most appear unaffected. A further significant question remaining is that if death of some muscle fibers is normal and perhaps advantageous (that is, by removing malfunctioning cells), what is the capacity for muscle fiber regeneration in adult skeletal muscle and can this process be augmented in aging muscles?     

Anaerobic performance in masters athletes

With increasing age, it appears that masters athletes competing in anaerobic events (10–100 s) decline linearly in performance until 70 years of age, after which the rate of decline appears to accelerate. This decline in performance appears strongly related to a decreased anaerobic work capacity, which has been observed in both sedentary and well-trained older individuals. Previously, a number of factors have been suggested to influence anaerobic work capacity including gender, muscle mass, muscle fiber type, muscle fiber size, muscle architecture and strength, substrate availability, efficiency of metabolic pathways, accumulation of reaction products, aerobic energy contribution, heredity, and physical training. The effects of sedentary aging on these factors have been widely discussed within literature. Less data are available on the changes in these factors in masters athletes who have continued to train at high intensities with the aim of participating in competition. The available research has reported that these masters athletes still demonstrate age-related changes in these factors. Specifically, it appears that morphological (decreased muscle mass, type II muscle fiber atrophy), muscle contractile property (decreased rate of force development), and biochemical changes (changes in enzyme activity, decreased lactate production) may explain the decreased anaerobic performance in masters athletes. However, the reduction in anaerobic work capacity and subsequent performance may largely be the result of physiological changes that are an inevitable result of the aging process, although their effects may be minimized by continuing specific high-intensity resistance or sprint training.     

The insulin-like growth factor-I receptor: Implications for the aging process

Aging is associated with decreased levels of growth hormone and both circulating and local levels of insulin-like growth factor-I (IGF-I). The decline in IGF-I has been postulated to be important in both physiological aging and pathological states that are seen with aging. In parallel, inappropriate apoptosis is thought to play a role in some of these same processes. In experimental models, IGF-I signalling through the IGF-I receptor confers a protective effect from apoptosis. This review summarizes the results of studies documenting the IGF-I anti-apoptotic effect in neuronal model systems. The known downstream signalling cascades that mediate this signal are beginning to be elucidated; these include MAP kinase and Akt. In addition, IGF-I prevents the reduction of anti-apoptotic proteins of the bcl-2 family induced by hyperosmotic conditions in cultured neuronal cells. IGF-I has been shown to positively impact on tau, the microtubule-associated protein, possibly preventing the degradation of proteins that are associated with the neurofibrils seen in Alzheimer's disease. All of the studies to date support the hypothesis that appropriately high levels of IGF-I signalling prevent some of the processes associated with aging.     

The effect of aging on skeletal-muscle recovery from exercise: possible implications for aging athletes

Recovery from exercise is integral to the physical training process. There is a perception among older athletes that aging negatively affects the recovery process. Plausible arguments for an impaired recovery with aging are a greater susceptibility of older muscle to exercise-induced skeletal-muscle damage and a slower repair and adaptation response. Differences in the physical activity level of the research participants are rarely considered, however. This makes it difficult to differentiate the respective roles of declining physical activity and aging on the recovery process. Furthermore, the type of exercise used to induce damage and monitor recovery is often not indicative of a normal training stimulus for athletes. This review discusses the effects of aging on skeletal-muscle damage and recovery processes and highlights the limitations of many of these studies with respect to older athletes. Future research should use an exercise intervention representative of a normal training stimulus and take the physical activity level of the participants into account.     

Physical exercise,nutrition and hormones: three pillars to fight sarcopenia

Background: Sarcopenia is a pathophysiological condition diffused in elderly people; it represents a social issue due to the longer life expectancy and the growing aging population. It affects negatively quality of life and it represents a risk factor for other pathologies, such as diabetes, cardiovascular disease, and obesity. No silver bullet exists to hinder sarcopenia, but it may be counteracted by physical exercise, nutrition, and a proper endocrine milieu. Indeed, we aim to analyze the scientific literature to give to clinician effective advices to counteract sarcopenia.

Main text: Physical exercise, proper nutrition, optimized hormonal homeostasis represent the three pillars to fight sarcopenia. Physical exercise represents the most effective remedy to face sarcopenia, in particular if it is combined with a proper diet and with an adequate endocrine milieu. Consistency in training, adequate daily protein intake and eugonadism seems to be the keys to fight sarcopenia. The combination of these three pillars might act synergistically.

Conclusions: Optimization of these factors may increase their efficiency; however, scientific data may be sometimes confusing so far. Therefore, we aim to give practical advices to clinician to identify and to highlight the most important aspects in each of these three factors that should be addressed.     

Anabolic responses to resistance training in older men and women: a brief review

Resistance training has been shown to be the most effective exercise mode to induce anabolic adaptations in older men and women. Advances in imaging techniques and histochemistry have increased the ability to detect such changes, confirming the high level of adaptability that remains in aging skeletal muscle. This brief review presents a summary of the resistance-training studies that directly compare chronic anabolic responses to training in older (>60 years) men and women. Sixteen studies are summarized, most of which indicate similar relative anabolic responses between older men and women after resistance training. Relatively small sample sizes in most of the interventions limited their ability to detect significant sex differences and should be considered when interpreting these studies. Future research should incorporate larger sample sizes with multiple measurement time points for anabolic responses.     

Endurance performance in masters athletes

Masters athletes are typically older than 35 years of age and systematically train for, and compete in, organized forms of sport specifically designed for older adults. They are motivated to participate in masters sport for a wide variety of reasons. Age-related declines in endurance performance are observed across the endurance sports of running, orienteering, rowing, and swimming. These declines are curvilinear from age 35 years until approximately age 60–70 years and exponential thereafter. The decline in endurance performance appears primarily due to an age-related decrease in VO_2max secondary to an age-related decrease in HR_max and possible age-related declines in stroke volume and arteriovenous oxygen difference. While performance velocity at lactate threshold decreases with age in masters endurance athletes, it appears to increase relative to VO_2max while exercise economy is maintained. There also appears an age-related decrease in active muscle mass, type II muscle fiber size, and blood volume that contribute to decreased endurance performance. However, research suggests that maintenance of training intensity and volume into older age may mediate the rate of age-related decline in VO_2max, stroke volume, arteriovenous oxygen difference, blood volume, and muscle mass in masters endurance athletes.     

Uncomplicated diabetes does not accelerate age-related sarcopenia

Abstract

Background: Diabetes is reported to accelerate sarcopenia (age-related loss of muscle mass and function). We aimed to assess muscle mass and strength in elderly diabetics, elderly non-diabetics, younger diabetics and healthy subjects, and to define correlates of muscle mass and strength in these subjects.

Methods: Sixteen elderly diabetics, 16 younger diabetics, 16 elderly non-diabetics and 18 younger non-diabetics were included. Elderly and diabetic subjects were first evaluated with exercise testing. Isokinetic leg extension and flexion tests were performed using a Cybex 350 dynamometer. Muscle mass was calculated using bioelectric impedance analysis.

Results: Muscle mass was similar between all groups; however, muscle strength was significantly lower in diabetic and non-diabetic elderly subjects compared with younger diabetic subjects and non-diabetics. Muscle strength was positively correlated with albumin, metabolic equivalent and hemoglobin, and inversely correlated with age, HbA1c, functional capacity and CRP. Independent correlates of muscle strength were age and hemoglobin. There was no clinically significant correlate of muscle mass. Presence or duration of diabetes was not associated with muscle mass or strength.

Conclusions: Uncomplicated diabetes does not seem to accelerate aging-related muscle mass or strength loss. Exercise test parameters may be useful markers in the screening of sarcopenia.     

The beneficial effects of different types of exercise interventions on motor and cognitive functions in older age: a systematic review

The decline in cognitive and motor functions with age affects the performance of the aging healthy population in many daily life activities. Physical activity appears to mitigate this decline or even improve motor and cognitive abilities in older adults. The current systematic review will focus mainly on behavioral studies that look into the dual effects of different types of physical training (e.g., balance training, aerobic training, strength training, group sports, etc.) on cognitive and motor tasks in older adults with no known cognitive or motor disabilities or disease. Our search retrieved a total of 1095 likely relevant articles, of which 41 were considered for full-text reading and 19 were included in the review after the full-text reading. Overall, observations from the 19 included studies conclude that improvements on both motor and cognitive functions were found, mainly in interventions that adopt physical-cognitive training or combined exercise training. While this finding advocates the use of multimodal exercise training paradigms or interventions to improve cognitive-motor abilities in older adults, the sizeable inconsistency among training protocols and endpoint measures complicates the generalization of this finding.     

Age-related variations in the growth hormone response to growth hormone secretagogues

Growth hormone (GH) secretagogues are synthetic peptidyl and non-peptidyl molecules which possess a strong, dose-dependent and reproducible GH-releasing effect after intravenous and even oral administration in humans. This effect is probably mediated via the activation of specific receptors, mainly present at the pituitary and hypothalamic level; a human pituitary GH secretogogue receptor has already been cloned, pointing to the existence of an endogenous GH secretagogue-like ligand. The GH-releasing effect of GH secretagogues is gender-independent but undergoes marked age-related variations. In fact, the effect is low at birth, increases markedly at puberty, persists at a similar level in adulthood and decreases thereafter, being already similar in middle age to that in elderly subjects. It is likely that the reduced activity of GH secretagogues in aging reflects the age-related changes in the neural control of somatotrope function. These could include the hypothetical impairment in the activity of the putative natural GH secretagogue-like ligand. Prolonged treatment with non-peptidyl GH secretagogues has been shown to restore spontaneous GH pulsatility and insulin-like growth factor I (IGF-I) levels in aged humans as well as in animals. The possibility that chronic treatment with GH secretagogues in aging rejuvenates the activity of the GH/IGF-I axis and counteracts the age-related changes in body composition, structure functions and metabolism seems very attractive.     

Endurance exercise and leg strength in older women

Quadriceps strength and mass peak in the third decade of life, plateau, and then decline from the fifth decade on. To examine the influence of chronic endurance training and age on lean mass and leg strength, women runners (n = 62, age 43-69 years) and sedentary participants (n = 33, age 43-66 years) were divided into 40-, 50-, and 60-year age groups. Absolute isokinetic concentric torque did not differ between runners and sedentary women (97.9 +/- 19.5 and 104.6 +/- 22.7 N . m, respectively, p = .18) but was different between age groups independent of exercise status (107.6 +/- 18.4, 97.1 +/- 19.9, and 90.1 +/- 21.4 N . m, for 40s, 50s, and 60s, respectively, p < .05). Lean body mass also differed by age group (p < .05) but did not change differently among runners and sedentary women. These findings suggest that chronic endurance training might not influence the loss of muscle mass and muscle strength that occur with aging.     

Identification and treatment of older persons with sarcopenia

Abstract

In the last decades, sarcopenia in older persons has been operationalized by the assessment of lean body mass, muscle strength and/or physical performance. Several definitions of sarcopenia, using different parameters and cut-offs, have been proposed. However, which is the best definition to describe and to assess this condition is still matter of debate. Hand grip strength has been suggested as better predictor of incident mobility impairment and mortality, than skeletal muscle mass. In the light of the current knowledge, we sought to propose an operative approach for identifying and treating sarcopenic older persons according to main categories of sarcopenia: the age-related or primary sarcopenia and disease-related or secondary sarcopenia. We suggest that a quantitative assessment of grip strength alone might be sufficient to identify patients with primary sarcopenia. When chronic diseases accompany the ageing process, the combined assessment of muscle strength plus a balance test could be more appropriate. The identification of tests and pathological relevant cut-offs that facilitates the entry of sarcopenia into the clinical practice, could step forward researchers and physicians. This could be important for planning multidisciplinary models to maximize the maintenance of locomotive abilities especially in older persons affected by chronic diseases such as Parkinson’s disease.     

Lower urinary tract symptoms and its potential relation with late-onset hypogonadism

The study of the health status of the aging male takes presently a more integrative approach and it appears that ailments typical of male aging, such as lower urinary tract symptoms (LUTS), (visceral) obesity, metabolic syndrome and erectile failure are significantly interrelated. A common denominator of the above ailments is lower-than-normal testosterone levels occurring in a significant proportion of elderly men. This review addresses the potential connections between LUTS and late-onset hypogonadism. In animal studies there appear to be androgen and estrogen receptors in the urothelium and smooth muscle cells of the urethra and bladder of the rat and rabbit, as well as in the neurons in the autonomic ganglia of the prostatic plexus of the male rat. Upon castration electrically evoked relaxations of the smooth muscle of the prostatic urethra were decreased. There is a Rho-kinase activation/endothelin pathway; possibly involved in the increased smooth muscle activity found in both LUTS/benign prostate hyperplasia. Nitric oxide (NO) appears to have a smooth muscle relaxing effect in the urogenital organs. Studies in humans have convincingly shown that phosphodiestererase inhibitors have a beneficial effect on LUTS. More intervention studies should be undertaken to test the clinical validity of the theoretically plausible interrelationship between LUTS and late-onset hypogonadism.     

Effects of aging on Type II muscle fibers: a systematic review of the literature

The authors conducted a systematic review of the literature for scientific articles in selected databases to determine the effects of aging on Type II muscle fibers in human skeletal muscles. They found that aging of Type II muscle fibers is primarily associated with a loss of fibers and a decrease in fiber size. Morphological changes with increasing age particularly included Type II fiber grouping. There is conflicting evidence regarding the change of proportion of Type II fibers. Type II muscle fibers seem to play an important role in the aging process of human skeletal muscles. According to this literature review, loss of fibers, decrease in size, and fiber-type grouping represent major quantitative changes. Because the process of aging involves various complex phenomena such as fiber-type coexpression, however, it seems difficult to assign those changes solely to a specific fiber type.     

Dividing to keep muscle together: the role of satellite cells in aging skeletal muscle

The factors responsible for the atrophy of skeletal muscle with aging remain to be elucidated. Recent evidence points toward an important role for a population of cells located on the surface of skeletal muscle fibers, known as satellite cells, in maintaining the integrity of skeletal myocytes throughout the life span. This Perspective examines the role that these cells are thought to play in aging muscle atrophy, and highlights a recent study by Brack and colleagues that attempts to understand the role of satellite cells in maintaining the ratio of myonuclear number to cytoplasmic volume within myocytes as we age.     

The differences of sarcopenia-related phenotypes: effects of gender and population

Sarcopenia is a serious condition especially in the elderly population mainly characterized by the loss of skeletal muscle mass and strength with aging. Extremity skeletal muscle mass index (EMMI) (sum of skeletal muscle mass in arms and legs/height²) is gaining popularity in sarcopenia definition (less than two standard deviations below the mean of a young adult reference group), but little is known about the gender- and population-specific differences of EMMI. This study aimed at investigating the differences of EMMI, arm muscle mass index (AMMI), and leg muscle mass index (LMMI) between gender groups and populations (Chinese vs. Caucasians). The participants included 1,809 Chinese and 362 Caucasians with normal weight aged from 19 to 45 years old. Extremity muscle mass, arm muscle mass, and leg muscle mass were measured by using dual energy x-ray absorptiometry. Independent sample t tests were used to analyze the differences in muscle mass indexes between the studied groups. All the study parameters including EMMIs, AMMIs, and LMMIs were significantly higher (P ≤ 0.0003) in the Caucasian group than in the Chinese group and also higher in the male group than in the female group, and these significant differences (P ≤ 0.0005) remained after adjusting for age by simple regressions. The detected differences of muscle mass indexes between different gender and ethnic groups may provide important implications in their different risk of future sarcopenia.     

Hypertension in aging: physical activity as primary prevention

In most physiologic systems, there is considerable evidence that the normal aging processes do not result in significant impairment or dysfunction in the absence of pathology and under resting conditions. However, in response to a stress, the age-related reduction in physiologic reserves causes a loss of regulatory or homeostatic balance. This happens before an individual notices that something is wrong. An additional consequence of age-related changes is an increased perception of effort associated with submaximal work. Thus, a vicious cycle is set up, leading to decreasing exercise capacity, resulting in an elevated perception of effort, subsequently causing avoidance of activity, and finally feeding back to exacerbation of the age-related declines secondary to disuse. Sedentary behavior is an important risk factor for chronic disease morbidity and mortality in aging. However, there is a limited amount of information on the type and amount of activity needed to promote optimal health and function in older people [19]. The purpose of this review is to discuss the important role of exercise training as a primary prevention tool to hypertension. In addition, this review will address the topic of the recommended amount of physical activity required for health promotion along with the current exercise guidelines.