Clinical effects of growth hormone on bone: a review

Growth hormone (GH) stimulates bone turnover. Deficiency of GH due to hypopituitarism is related to low bone mineral density and increased fracture risk. GH substitution increases and thus normalizes bone mineral density in these patients, which is one of a number of arguments for GH substitution in hypopituitarism. In contrast, a possible therapeutic use of GH in idiopathic osteoporosis and glucocorticoid-induced osteoporosis is speculative and not established. Reduction of osteoporosis risk is an argument brought up for a use of GH in healthy elderly persons (anti-aging medicine). However, since only very limited data are available yet, this cannot be based on scientific evidence, and there are important concerns about the safety of use of GH in healthy elderly persons.     

Senility,illness and death in Açvaghosa's ‘Buddhacări˘ta’The Feats of Buddha

Background An age-related decline in growth hormone (GH) level has been established, and this decline is associated with changes in body composition as well as a general increase in susceptibility to illness and a reduced sense of well-being. The current study, a first in Asia, sought to examine the effects of GH therapy on body composition and other endocrine and metabolic functions in a group of healthy elderly Chinese men.

Methods A total of 23 healthy elderly Chinese men, aged between 60 and 69 years, were injected subcutaneously, three times weekly, with 0.08 U/kg of recombinant GH for 6 months. Various hormones and biochemical parameters, together with percentage lean body mass and body fat, were measured before, 3 and 6 months after the start and 3 months after the cessation of GH therapy.

Results A significant increase in lean body mass, up to 9.1% over baseline values at 3 months post-therapy, and a significant decrease in body fat, up to 3.1%, were noted. GH therapy also induced variable and significant increases in levels of insulin growth factor (IGF-I), dehydroepiandrosterone sulfate (DHEAS), insulin, triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH) and triglyceride and significant reductions in glucose and sex hormone binding globulin (SHBG) levels. No changes in testosterone, free androgen index and cholesterol were noted. A significant and independent correlation was noted between IGF-I and insulin, TSH, DHEAS, glucose and triglyceride levels.

Conclusions GH augmentation therapy was effective in improving the body composition of a group of elderly Chinese men. GH-induced positive changes in body composition in the elderly were probably a result of the direct effect of the GH. It is also possible that some of the changes were mediated through GH-induced changes in thyroid hormones, insulin, glucose, triglyceride and DHEAS. However, the mechanism of GH- induced changes in body composition remains to be defined.     

Alterations in IGF-I affect elderly: role of physical activity

The growth hormone–insulin-like growth factor I (IGF-I) axis is an important physiological regulator muscle for development. Although there is evidence that aging muscle retains the ability to synthesize IGF-I, there is also evidence that aging may be associated with attenuation of the ability of exercise to induce an isoform of IGF-I that promotes satellite cell proliferation. However, it is clear that overexpression of IGF-I in the muscle can protect against age-related sarcopenia. Strength training appears to be the intervention of choice for the prevention and treatment of sarcopenia. IGF-I has been implicated in the loss of the muscle with age, and IGF-I expression levels change as a consequence of strength training in older adults. However, it seems that advancing age, rather than declining serum levels of IGF-I, appears to be a major determinant of life-time changes in body composition in women and men. We concluded that resistive exercise is a significant determinant of muscle mass and function. Elevated levels of IGF-I have been found in physically active compared to sedentary individuals. Recent work suggests that IGF-I as a mediator plays an important role in muscle hypertrophy and angiogenesis, both of which characterize the anabolic adaptation of muscles to exercise.     

Does the road to muscle rejuvenation go through Notch?

The capacity of skeletal muscles to repair and regenerate declines during aging in humans, and this decline may lead to muscle loss and frailty. Conboy et al. show that injured muscles of aging mice are defective in Notch signaling, because up-regulation of the Notch ligand, Delta-1, is impaired. Delta-1 promotes proliferation of the satellite cells that repair damaged muscles, and Conboy et al. show that experimental activation of Notch signaling is sufficient to reverse the age-related decline in muscle regenerative capacity. Extension of these important findings to humans could lead to the development of new therapeutic approaches to maintain muscle function during aging.     

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.     

Not wisely but too well: aging as a cost of neuroendocrine activity

Progressive decline of some neuroendocrine signaling systems has long been assumed to cause age-related physiological impairments and limit life span. However, hypophysectomy--removal of the pituitary gland--can delay many aspects of the aging process, and recent genetic studies have confirmed that reducing the secretion of pituitary hormones can increase the life span of laboratory organisms. Most strikingly, reducing activity of the insulin/insulin-like growth factor-1 signaling system substantially increases life span. Conversely, activity of the reproductive system or activation of stress responses can curtail life span. Because caloric restriction also reduces the activity of several neuroendocrine systems while increasing life span, it now appears that the aging process is driven, at least in part, by neuroendocrine activity rather than by its decline with age.     

High-intensity interval training (HIIT) increases insulin-like growth factor-I (IGF-I) in sedentary aging men but not masters’ athletes: an observational study

Introduction: The aim of this investigation was to examine the impact high-intensity interval training (HIIT) on serum insulin-like growth factor-I (IGF-I) in active compared with sedentary aging men.

Methods: 22 lifetime sedentary (SED; 62?±?2 years) and 17 masters’ athletes (LEX; 60?±?5 years) were recruited to the study. As HIIT requires preconditioning exercise in sedentary cohorts, the study required three assessment phases; enrollment (phase A), following preconditioning exercise (phase B), and post-HIIT (phase C). Serum IGF-I was determined by electrochemiluminescent immunoassay.

Results: IGF-I was higher in LEX compared to SED at baseline (p?=?0.007, Cohen’s d?=?0.91), and phase B (p?=?0.083, Cohen’s d?=?0.59), with only a small difference at C (p?=?0.291, Cohen’s d?=?0.35). SED experienced a small increase in IGF-I following preconditioning from 13.1?±?4.7 to 14.2?±?6.0?μg·dl^?1 (p?=?0.376, Cohen’s d?=?0.22), followed by a larger increase post-HIIT (16.9?±?4.4?μg·dl^?1), which was significantly elevated compared with baseline (p?=?0.002, Cohen’s d?=?0.85), and post-preconditioning (p?=?0.005, Cohen’s d?=?0.51). LEX experienced a trivial changes in IGF-I from A to B (18.2?±?6.4 to 17.2?±?3.7?μg·dl^?1 [p?=?0.538, Cohen’s d?=?0.19]), and a small change post-HIIT (18.4?±?4.1?μg·dl^?1 [p?=?0.283, Cohen’s d?=?0.31]). Small increases were observed in fat-free mass in both groups following HIIT (p?d?=?0.32–0.45).

Conclusions: In conclusion, HIIT with preconditioning exercise abrogates the age associated difference in IGF-I between SED and LEX, and induces small improvements in fat-free mass in both SED and LEX.     

Ubiquitin,proteasomes, and the aging brain

Ubiquitinated proteinaceous inclusions are the hallmark of many neurodegenerative diseases. Inefficient proteolysis might lead to the accumulation and ultimate deposition of potentially toxic entities as inclusions within neurons or glial cells. This hypothesis is supported by genetic evidence both from patient populations and from engineered mutations in genes that encode ubiquitin/proteasome components in mice. The appearance of similar inclusions in the brains of elderly individuals of normal and subclinical conditions begs the question of whether there is a general age-related decline in the ability of the ubiquitin/proteasome pathway (UPP) to recognize and eliminate abnormal proteins, and whether such a decline would be reflected by changes in the abundance or activity of some or all components of the UPP. Here we describe alterations in the aging mammalian brain that correlate with a decline in the function of the UPP and review the evidence for age-related changes in specific UPP components. These alterations are discussed within the context of prevalent theories of aging.     

Long-term low-dose dehydroepiandrosterone replacement therapy in aging males with partial androgen deficiency

Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) age-related withdrawal is very likely to be involved in the aging process and the onset of age-related diseases, giving rise to the question of whether preventing or compensating the decline of these steroids may have endocrine and clinical benefits. The aim of the present trial was to evaluate the endocrine, neuroendocrine and clinical consequences of a long-term (1 year), low-dose (25?mg/day) replacement therapy in a group of aging men who presented the clinical characteristics of partial androgen deficiency (PADAM). Circulating DHEA, DHEAS, androstenedione, total testosterone and free testosterone, dihydrotestosterone (DHT), progesterone, 17-hydroxyprogesterone, allopregnanolone, estrone, estradiol, sex hormone binding globulin (SHBG), cortisol, follicle stimulating hormone (FSH), luteinizing hormone (LH), growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels were evaluated monthly to assess the endocrine effects of the therapy, while β-endorphin values were used as a marker of the neuroendocrine effects. A Kupperman questionnaire was performed to evaluate the subjective symptoms before and after treatment.

The results showed a great modification of the endocrine profile; with the exception of cortisol levels, which remained unchanged, DHEA, DHEAS, androstenedione, total and free testosterone, DHT, progesterone, 17-hydroxyprogesterone, estrone, estradiol, GH, IGF-1 and β-endorphin levels increased significantly with respect to baseline values, while FSH, LH and SHBG levels showed a significant decrease. The Kupperman score indicated a progressive improvement in mood, fatigue and joint pain.

In conclusion, the present study demonstrates that 25?mg/day of DHEA is able to cause significant changes in the hormonal profile and clinical symptoms and can counteract the age-related decline of endocrine and neuroendocrine functions. Restoring DHEA levels to young adult values seems to benefit the age-related decline in physiological functions but, however promising, placebo-controlled trials are required to confirm these preliminary results.     

Federalism and aging policy in the 1980s: implications for changing interest group roles in the 1990s

Shifts in the American political landscape during the 1980s had impacts on aging policy and on the behavior of aging interest groups through that decade. But perhaps even more important are the likely effects of those changes on aging policy and on the roles of age-related groups in the 1990s--and probably beyond. First, some of the major policy trends of the 1980s are sketched out, especially the renewed emphasis on federalism. Then, an assessment of their effects on aging policy and aging interest groups is provided. Next, a rationale for focusing on state-level policy and a discussion of current aging interest-group mobilization at the state level are presented. Last, the prospects for aging interest-group influence in the 1990s--a period in which the prior decade's emphasis on dual federalism is likely to continue--is addressed.     

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.     

Age-related slowing of movement as basal ganglia dysfunction

Attributions of age-related deficits in motor function to structural changes are compromised once the elderly exhibit lower error rates. This is because performance decrements observed in older adults are attributed to inferred strategic preferences for accuracy over speed. To understand genuine age differences in performance, we argue in the following theoretical paper that research needs to resolve methodological shortcomings and account for them within theoretical models of aging. Accounts of aging need to directly manipulate or control strategic differences in performance while assessing structural deficits. When this is done, age-related changes in motor control resemble the intermittencies of control seen in basal ganglia disorders. Given homologous circuitry in the basal ganglia, such observations could generalize to age-related changes in cognitive and emotional processes.     

A life course approach: research orientations and future challenges

The need to study lifelong changes in health and functioning has resulted in increasing emphasis on a life course approach in different fields of inquiry. The aim of this approach is to explore how biological, psychological, and social risk factor trajectories, acting across the entire life course, influence age-related diseases, functional decline, and disability. The importance of the first years of life upon later development and adult characteristics was generally recognized already in the first half of the twentieth century, but it was not until the 1990s that different strands of medical and social research converge in the field of life course epidemiology, in which epidemiological processes are approached using different models such as biological programming, critical periods, pathways, and accumulation. The biological programming model holds that organ development in utero and early infancy determines the maximum functional capacity that an individual can attain and influences the development of certain chronic diseases later in life. The critical period model extends the idea to include child development and key social transitions over the entire life course. The pathway model focuses on the cumulative effect of life events along the developmental trajectories, with early advantage or disadvantage setting a person on a pathway to a later etiologically important exposure. The accumulation model describes the underlying social, behavioral, and biological processes that drive the impact of the life course on health. The growing focus on life course determinants of aging also has implications for studies of long-term changes in physical activity and their role in determining both gains and losses of health and functioning with aging. A life course approach presents great challenges for the continued development of testable theoretical models and effective study design and analysis.     

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.     

Aging effects on joint proprioception: the role of physical activity in proprioception preservation

Throughout the human life span the functions of several physiological systems dramatically change, including proprioception. Impaired proprioception leads to less accurate detection of body position changes increasing the risk of fall, and to abnormal joint biomechanics during functional activities so, over a period of time, degenerative joint disease may result. Altered neuromuscular control of the lower limb and consequently poor balance resulting from changes in the proprioceptive function could be related to the high incidence of harmful falls that occur in old age subjects. There is evidence of proprioception deterioration with aging. Regular physical activity seems to be a beneficial strategy to preserve proprioception and prevent falls among older subjects. Some studies have demonstrated that the regular physical activity can attenuate age-related decline in proprioception. This paper reviews the evidence of age effects on joint proprioception. We will discuss the possible mechanisms behind these effects and the role of regular physical activity in the attenuation of age-related decline in proprioception.     

Health-related quality of life in old age: preliminary report on the male perspective

Health-related quality of life is a key element of successful aging. With life expectancy increasing, postmenopausal estrogen/gestagen replacement therapy has been under discussion for some time with the aim of achieving a higher quality of life in old age. For a long time, the relevance of hormonal aging was only discussed with reference to women; however, more recent work deals with concepts that affect both sexes. According to recent studies, numerous symptoms and complaints which may impair quality of life, can be attributed to hormonal changes in old age in both women and men. The majority of age-related complaints, such as a decline in physical performance, decreased sexual activity and a deterioration of general well-being, are strongly reminiscent of the symptoms of classical pituitary disorders in adulthood. Since the early 1990s, scientific studies have also been investigating the influence of hormone 'replacement' in elderly men, using, for example, growth hormones. However, until now there has been no suitable measure for assessing the quality of life specifically in elderly men. In a research project aimed at developing a questionnaire (the VITA? questionnaire), roughly equal numbers of elderly men and women were asked about their subjective health and quality of life. It was found that men assessed their health-related quality of life very positively in a number of different dimensions of the questionnaire. In the present article the individual aspects of the quality of life of men are described and examples of gender-related differences are presented and discussed.     

Nutrition of the elderly: Interactions with physical activity

Elderly subjects have a lower energy requirement compared to young adults as a result of lower physical activity and a lower basal metabolic rate. A lower energy intake in the elderly could lead to undesirable low intakes of essential nutrients. The reduction of the energy turnover is caused by, or a consequence of, a decrease in active cell mass. Thus, the effect of exercise training on habitual activity across age ranges, and age-related changes in body composition in relation to habitual activity level, are investigated here. The focus is on data on physical activity and body composition obtained with doubly labelled water. The results suggest that exercise training does not affect energy requirement in the elderly and the age-related decrease in fat-free mass is not delayed in subjects with a relatively high habitual activity level. Beneficial effects of exercise training in the elderly are endurance, flexibility, range of motion and balance control, all contributing to a delay in the age-induced impairment of personal mobility. Energy intake will inevitably go down as a result of a reduction of the energy requirement. Thus, the nutrition of elderly subjects needs more attention with regard to the essential nutrients than the nutrition of younger adults.     

Creating new neurons in old brains

The brains of aged rodents exhibit decreased neurogenesis as compared to those of young adult rodents. Basal neurogenesis has previously been shown to increase in the young adult rodent brain upon the administration of growth factors. However, it is unknown whether similar treatment can affect this process in the aging brain. A recent paper published in the June 2003 issue of the journal Aging Cell reveals that two growth factors can stimulate neurogenesis in aged mice. This result raises the possibility that similar treatments may be used in humans to help maintain normal brain function in old age.     

Health Status and Health Care Services Among Older Persons in India

Summary

India is characterized by significant rural-based living, population heterogeneity, financial constraints, and reverse sex ratio. Traditions of joint families, life-long physical activity, vegetarianism, and social and spiritual enrichment, all known to promote healthy aging, are widely prevalent. With the increasing pace of population aging, the health of older persons in India has been the focus of recent attention. Existing data indicate a significant morbidity among the aged, much of which may remain subclinical. Considerable variations in morbidity exist with respect to gender, place of residence (rural vs. urban), and socioeconomic status. Rapid demographic transition without a concomitant epidemiological transition is responsible for the dual load of infections and degenerative diseases in older persons, these being common causes of death. Most age-related morbidity is preventable. Health promotion and cost-effective interventions based on the primary health care approach over a lifelong course, especially at the village level, will greatly help towards achieving the goal of healthy aging. The rapidly changing socioeconomic scenario in India also calls for appropriate policy actions to achieve this goal.     

Neuropsychology and cognitive health in healthy older adults: a brief overview for psychiatric nurses

This article contains a brief synopsis on nonpathological aspects of the neuropsychology of aging and cognitive health. In nonpathological aging, normal subtle decline occurs in a number of cognitive domains such as executive functioning, speed of processing, memory, language, and psychomotor ability; however, some domains of cognitive functioning appear to increase with age, such as vocabulary and crystallized intelligence. In the neuropsychology and the cognitive aging literatures, several hypotheses for such age-related declines are proposed, including the diminished speed-of-processing hypothesis, the common cause hypothesis, and the frontal aging hypothesis. As these age-related changes diminish cognitive reserve, the decline in the related cognitive domains emerges. Ways to protect and improve cognitive health are suggested to encourage positive neuroplasticity and discourage negative neuroplasticity. Implications for nursing practice are provided.