L. Dominguez

Magnesium and aging.

Over the past decades, the clinical relevance and biological significance of magnesium (Mg) have been documented. Deficiency in Mg, aside from having a negative impact on the energy production pathway required by mitochondria to generate ATP, also reduces the threshold antioxidant capacity of the aging organism and its resistance to free-radical damage. Mg also acts as an antioxidant against free radical damage of the mitochondria. Chronic inflammation and oxidative stress have both been identified as pathogenic factors in aging and in several age-related diseases. Chronic Mg deficiency results in excessive production of oxygen-derived free radicals and low grade inflammation. Aging is very often associated with Mg inadequacy and with increased incidence of many chronic diseases, with muscle loss and sarcopenia, altered immune responses, and vascular and metabolic conditions, such as atherosclerosis, diabetes and the cardiometabolic syndrome. The most common cause of Mg deficit in the elderly population is dietary Mg deficiency, although secondary Mg deficit in aging may also results from many different mechanisms. The aim of the present manuscript is to discuss the mechanisms and consequences of the modifications of Mg metabolism with age, the difficulties in the measurement of Mg status, and to review the current evidences suggesting that age-related chronic Mg deficits may be proposed as one of the physiopathological links that may help to explain the interactions between inflammation, oxidative stress with the aging process and many age-related diseases.

Senile anorexia in acute-ward and rehabilitations settings.

The most common pathological change in eating behaviour among older persons is anorexia, which accounts for a large percent of undernutrition in older adults. The main research aims are to determine, in a sample of acute and rehabilitation elderly subjects, the prevalence of anorexia of aging and the causes most impacting on senile anorexia.Methods: four different Units cooperated to this research study. Patients were recruited from geriatric acute and rehabilitation wards in Italy. Each Research Unit, for the estimation of the prevalence of anorexia in elderly subjects evaluated all the patients aged over 65 recruited from April 2006 to June 2007. Nutritional status, depression, social, functional and cognitive status, quality of life, health status, chewing, swallowing, sensorial functions were evaluated in anorexic patients and in a sample of “normal eating” elderly subjects.Results: 96 anorexic subjects were selected in acute and rehabilitation wards (66 women; 81.5±7 years; 30 men: 81.8±8 years. The prevalence of anorexia in the sample was 33.3% in women and 26.7% in men. Anorexic subjects were older and more frequently needed help for shopping and cooking. A higher (although not statistically significant) level of comorbidity was present in anorexic subjects. These subjects reported constipation and epigastrium pain more frequently. Nutritional status parameters (MNA, anthropometry, blood parameters) were significantly worst in anorexic subjects whereas CRP was higher. Chewing and swallowing efficiencies were significantly impaired and eating patterns were different for anorexic subjects with a significant reduction of protein rich foods.Conclusions: consequences of anorexia can be extremely serious and deeply affect both patient’s mobility, mortality and quality of life. Therefore, it is of utmost importance to perform a special evaluation of the nutritional risk, to constantly evaluate the nutritional status and feeding intake of older patients, to identify and treat the underlying disease when possible, to institute environmental and behavioural modifications, to organise staff better in order to produce higher quality feeding assistance during mealtimes, to plan early nutrition rehabilitation and nutritional education programs for caregivers. There is also the necessity to develop diagnostic procedures easy to perform, able to identify the pathogenesis of anorexia and, therefore, treatment strategies exactly fitting the patients’ needs.

Bisphosphonates and atherosclerosis: why?

The increasing knowledge on bone calcification processes has revealed some similarities with vascular tissue, where calcifications of arteries and cardiac valves contribute to several cardiovascular problems, such as heart failure, systolic hypertension, and myocardial and peripheral ischemic disease. Bisphosphonates have been used extensively for over two decades for the treatment of diseases associated with excessive bone resorption, i.e., osteoporosis, osteolytic bone metastasis, hypercalcemia and Paget’s disease, by blocking osteoclastic function. Etidronate, pamidronate and clodronate has been shown to inhibit the development of experimental atherosclerosis, and proposed mechanisms for this action include inhibition of arterial calcification and lipid accumulation, degradation of atherogenic LDL-cholesterol and reduced foam cell formation. Bisphosphonates inhibit various enzymes involved in cholesterol biosynthesis and suppress macrophages in atheromatous lesions. The possibility of pharmacological agents that effectively treat both osteoporosis and atherosclerosis is attractive, however, current evidence is not conclusive and further research is necessary to confirm these actions in the clinical setting.

Magnesium and anabolic hormones in older men

Optimal nutritional and hormonal statuses are determinants of successful ageing. The age associated decline in anabolic hormones such as testosterone and insulin-like growth factor 1 (IGF-1) is a strong predictor of metabolic syndrome, diabetes and mortality in older men. Studies have shown that magnesium intake affects the secretion of total IGF-1 and increase testosterone bioactivity. This observation suggests that magnesium can be a modulator of the anabolic/catabolic equilibrium disrupted in the elderly people. However, the relationship between magnesium and anabolic hormones in men has not been investigated. We evaluated 399 ≥65-year-old men of CHIANTI in a study population representative of two municipalities of Tuscany (Italy) with complete data on testosterone, total IGF-1, sex hormone binding globulin (SHBG), dehydroepiandrosterone sulphate (DHEAS) and serum magnesium levels. Linear regression models were used to test the relationship between magnesium and testosterone and IGF-1. Mean age of the population was 74.18 ± 6.43 (years ± SD, age range 65.2-92.4). After adjusting for age, magnesium was positively associated with total testosterone (β ± SE, 34.9 ± 10.3; p = 0.001) and with total IGF-1 (β ± SE, 15.9 ± 4.8; p = 0.001). After further adjustment for body mass index (BMI), log (IL-6), log (DHEAS), log (SHBG), log (insulin), total IGF-1, grip strength, Parkinsons disease and chronic heart failure, the relationship between magnesium and total testosterone remained strong and highly significant (β ± SE, 48.72 ± 12.61; p = 0.001). In the multivariate analysis adjusted for age, BMI, log (IL-6), liver function, energy intake, log (insulin), log (DHEAS), selenium, magnesium levels were also still significantly associated with IGF-1 (β ± SE, 16.43 ± 4.90; p = 0.001) and remained significant after adjusting for total testosterone (β ± SE, 14.4 ± 4.9; p = 0.01). In a cohort of older men, magnesium levels are strongly and independently associated with the anabolic hormones testosterone and IGF-1.

The Interplay between Magnesium and Testosterone in Modulating Physical Function in Men

The role of nutritional status as key factor of successful aging is very well recognized. Among the different mechanisms by which nutrients may exert their beneficial effects is the modulation of the hormonal anabolic milieu, which is significantly reduced with aging. Undernutrition and anabolic hormonal deficiency frequently coexist in older individuals determining an increased risk of mobility impairment and other adverse outcomes. Mineral assessment has received attention as an important determinant of physical performance. In particular, there is evidence that magnesium exerts a positive influence on anabolic hormonal status, including Testosterone, in men. In this review we summarize data from observational and intervention studies about the role of magnesium in Testosterone bioactivity and the potential underlying mechanisms of this relationship in male subjects. If larger studies will confirm these pivotal data, the combination of hormonal and mineral replacements might be adopted to prevent or delay the onset of disability in the elderly.