Sarcopenia in Asia: consensus report of the Asian Working Group for Sarcopenia.

During the last decade, the GH axis has become the compelling focus of remarkably active and broad-ranging basic and clinical research. Molecular and genetic models, the discovery of human GHRH and its receptor, the cloning of the GHRP receptor, and the clinical availability of recombinant GH and IGF-I have allowed surprisingly rapid advances in our knowledge of the neuroregulation of the GH-IGF-I axis in many pathophysiological contexts. The complexity of the GHRH/somatostatin-GH-IGF-I axis thus commends itself to more formalized modeling (154, 155), since the multivalent feedback-control activities are difficult to assimilate fully on an intuitive scale. Understanding the dynamic neuroendocrine mechanisms that direct the pulsatile secretion of this fundamental growth-promoting and metabolic hormone remains a critical goal, the realization of which is challenged by the exponentially accumulating matrix of experimental and clinical data in this arena. To the above end, we review here the pathophysiology of the GHRH somatostatin-GH-IGF-I feedback axis consisting of corresponding key neurotransmitters, neuromodulators, and metabolic effectors, and their cloned receptors and signaling pathways. We propose that this system is best viewed as a multivalent feedback network that is exquisitely sensitive to an array of neuroregulators and environmental stressors and genetic restraints. Feedback and feedforward mechanisms acting within the intact somatotropic axis mediate homeostatic control throughout the human lifetime and are disrupted in disease. Novel effectors of the GH axis, such as GHRPs, also offer promise as investigative probes and possible therapeutic agents. Further understanding of the mechanisms of GH neuroregulation will likely allow development of progressively more specific molecular and clinical tools for the diagnosis and treatment of various conditions in which GH secretion is regulated abnormally. Thus, we predict that unexpected and enriching insights in the domain of the neuroendocrine pathophysiology of the GH axis are likely be achieved in the succeeding decades of basic and clinical research.

Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human

Most aging individuals die from atherosclerosis, cancer, or dementia; but in the oldest old, loss of muscle strength resulting in frailty is the limiting factor for an individual's chances of living an independent life until death. Three hormonal systems show decreasing circulating hormone concentrations during normal aging: (i) estrogen (in menopause) and testosterone (in andropause), (ii) dehydroepiandrosterone and its sulphate (in adrenopause), and (iii) the growth hormone/insulin-like growth factor I axis (in somatopause). Physical changes during aging have been considered physiologic, but there is evidence that some of these changes are related to this decline in hormonal activity. Hormone replacement strategies have been developed, but many of their aspects remain controversial, and increasing blood hormone levels in aging individuals to those found during mid-adult life has not been uniformly proven to be safe and of benefit.

/pdf/the-endocrinology-of-aging-1tkdm0zmpp.pdf

The Endocrinology of Aging

Sarcopenia is a loss of muscle protein mass and loss of muscle function. It occurs with increasing age, being a major component in the development of frailty. Current knowledge on its assessment, etiology, pathogenesis, consequences and future perspectives are reported in the present review. On-going and future clinical trials on sarcopenia may radically change our preventive and therapeutic approaches of mobility disability in older people.

/pdf/sarcopenia-its-assessment-etiology-pathogenesis-consequences-44lsxabedh.pdf

Sarcopenia: Its assessment, etiology, pathogenesis, consequences and future perspectives

During the aging process, mammals lose up to a third of their skeletal muscle mass and strength. Although the mechanisms underlying this loss are not entirely understood, we attempted to moderate the loss by increasing the regenerative capacity of muscle. This involved the injection of a recombinant adeno-associated virus directing overexpression of insulin-like growth factor I (IGF-I) in differentiated muscle fibers. We demonstrate that the IGF-I expression promotes an average increase of 15% in muscle mass and a 14% increase in strength in young adult mice, and remarkably, prevents aging-related muscle changes in old adult mice, resulting in a 27% increase in strength as compared with uninjected old muscles. Muscle mass and fiber type distributions were maintained at levels similar to those in young adults. We propose that these effects are primarily due to stimulation of muscle regeneration via the activation of satellite cells by IGF-I. This supports the hypothesis that the primary cause of aging-related impairment of muscle function is a cumulative failure to repair damage sustained during muscle utilization. Our results suggest that gene transfer of IGF-I into muscle could form the basis of a human gene therapy for preventing the loss of muscle function associated with aging and may be of benefit in diseases where the rate of damage to skeletal muscle is accelerated.

http://www.pnas.org/content/95/26/15603.full.pdf

Viral mediated expression of insulin-like growth factor I blocks the aging-related loss of skeletal muscle function

Objective: To determine whether growth hormone replacement in older men improves functional ability. Design: Randomized, controlled, double-blind trial. Setting: General community. Patients: 52 hea...

Growth Hormone Replacement in Healthy Older Men Improves Body Composition but Not Functional Ability

The hypothesis that loss of tissue mass in the foot contributes to foot ulceration in diabetics has never been quantitated. We developed normal criteria for the thickness of the sole of the foot at the heel, and the five metatarsal heads of both feet, using high-resolution ultrasound (10 MHz). We studied 24 normal patients ranging in weight from 125 to 250 lbs. We examined the soles of the feet of 38 diabetics without foot ulcers and 11 diabetics with foot ulcers or a history of foot ulcers who were in the same weight range as the normals. Of statistical significance, the heel thickness in controls was greater than that of the diabetics, which in turn was greater than that of the diabetics with foot ulcers. The thickness of the sole over the first and second metatarsals was also greater in the controls compared with diabetics. We conclude that high-resolution ultrasound is an effective determinant of the thickness of the sole of the foot and that diabetics have variations from the norm in the heel and at the first and second metatarsal heads.

Sonography of the sole of the foot. Evidence for loss of foot pad thickness in diabetes and its relationship to ulceration of the foot.

Liquid crystal thermography (LCT) was used to determine temperature variations on the plantar surface of feet. The purpose was to identify thermal emission patterns associated with diabetic foot ulcers. Three population groups were screened: group I, 16 nondiabetic controls; group II, 21 diabetic patients with no history of pedal ulcers; and group III, 28 diabetic patients with active pedal ulceration or history of foot ulcerations. The results demonstrate a generalized increase in plantar foot temperature in group III compared with groups I and II. Temperature readings under metatarsal heads 1-5, great toe, heel, and lateral band were significantly increased (P less than .01) in group III. Additionally, the warm lateral surface displayed by group III patients was not significantly different in temperature from the medial arch of the foot. In groups I and II, the lateral band was significantly cooler (P less than .01) than the medial arch. In group III patients with active ulceration on only one foot, no significant difference in temperature was found between the foot with active ulceration compared with the contralateral nonulcerated foot. When patients with active pedal ulceration were compared with patients with a history of foot ulcers, no significant difference in temperature was seen at five of seven sites tested. A warm concentric color band surrounding active plantar ulcers was identified in group III. This pattern extended from the center of the ulcer to a distance of 8 mm. A significant change in temperature (P less than .01) was noted at 6- and 8-mm distances from the center of the ulcer. In addition, a mottled thermographic pattern was observed more frequently in group III patients than in groups I and II.(ABSTRACT TRUNCATED AT 250 WORDS)

Gretchen A. W. Gooding

Papers

Growth Hormone Replacement in Healthy Older Men Improves Body Composition but Not Functional Ability

Sonography of the sole of the foot. Evidence for loss of foot pad thickness in diabetes and its relationship to ulceration of the foot.

Use of Liquid Crystal Thermography in the Evaluation of the Diabetic Foot