Aging is very often associated with magnesium (Mg) deficit. Total plasma magnesium concentrations are remarkably constant in healthy subjects throughout life, while total body Mg and Mg in the intracellular compartment tend to decrease with age. Dietary Mg deficiencies are common in the elderly population. Other frequent causes of Mg deficits in the elderly include reduced Mg intestinal absorption, reduced Mg bone stores, and excess urinary loss. Secondary Mg deficit in aging may result from different conditions and diseases often observed in the elderly (i.e. insulin resistance and/or type 2 diabetes mellitus) and drugs (i.e. use of hypermagnesuric diuretics). Chronic Mg deficits have been linked to an increased risk of numerous preclinical and clinical outcomes, mostly observed in the elderly population, including hypertension, stroke, atherosclerosis, ischemic heart disease, cardiac arrhythmias, glucose intolerance, insulin resistance, type 2 diabetes mellitus, endothelial dysfunction, vascular remodeling, alterations in lipid metabolism, platelet aggregation/thrombosis, inflammation, oxidative stress, cardiovascular mortality, asthma, chronic fatigue, as well as depression and other neuropsychiatric disorders. Both aging and Mg deficiency have been associated to excessive production of oxygen-derived free radicals and lowgrade inflammation. Chronic inflammation and oxidative stress are also present in several age-related diseases, such as many vascular and metabolic conditions, as well as frailty, muscle loss and sarcopenia, and altered immune responses, among others. Mg deficit associated to aging may be at least one of the pathophysiological links that may help to explain the interactions between inflammation and oxidative stress with the aging process and many age-related diseases.

Magnesium deficiency is present in several chronic, age-related diseases, including cardiovascular, metabolic and neurodegenerative diseases. Alzheimer's disease (AD) is the most common cause of dementia. The aim of the present study was to study magnesium homeostasis in patients with mild to moderate AD. One hundred and one elderly (≥65 years) patients were consecutively recruited (mean age: 73.4±0.8 years; M/F: 42/59). In all patients, a comprehensive geriatric assessment was performed including cognitive and functional status. Admission criteria for the AD group (diagnosed according to the DSM-IV and the NINCDS-ADRDA criteria) included: mild to moderate cognitive impairment (MMSE score: 11-24/30, corrected for age and education). Blood samples were analyzed for serum total magnesium (Mg-tot) and serum ionized magnesium (Mg-ion). AD patients had significantly lower MMSE scores (20.5±0.7 vs 27.9±0.2; p<0.001), and for the physical function tests. Mg-ion was significantly lower in the AD group as compared to age-matched control adults without AD (0.50±0.01 mmol/L vs 0.53±0.01 mmol/L; p<0.01). No significant differences were found in Mg-tot between the two groups (1.91±0.03 mEq/L vs 1.95±0.03 mEq/L; p=NS). For all subjects, Mg-ion levels were significantly and directly related only to cognitive function (Mg-ion/MMSE r=0.24 p<0.05), while no significant correlations were found in this group of patients between magnesium and ADL or IADL. Our results show the presence of subclinical alterations in Mg-ion in patients with mild to moderate AD.

No abstract

Fragility fractures, a major public health concern, are expected to further increase due to aging of the world populations because age remains a cardinal, independent determinant of fracture risk. With aging the balance between bone formation and resorption during the remodeling process becomes negative, with increased resorption and reduced formation. Bisphosphonates (BPs) are widely prescribed anti-resorptive agents that inhibit osteoclasts attachment to bone matrix and enhance osteoclast apoptosis. BPs can be divided into nitrogen-containing (N-BPs) and non-nitrogen-containing BPs (non-N-BPs). Both classes induce apoptosis but they evoke it differently. Several studies have examined the molecular mechanisms underlying BPs' effects on osteoclasts and bone remodeling. N-BPs (alendronate, risedronate, zoledronate) inhibit the intracellular mevalonate pathway and protein isoprenylation, via the enzyme farnesyl pyrophosphate synthase. N-BPs act by competition, binding to the natural substrate-binding site of the enzyme. The less potent non-N-BPs (etidronate, clodronate), do not inhibit the mevalonate pathway and protein isoprenylation, but are metabolized intracellularly to metabolites, which are cytotoxic analogs of ATP. N-BPs represent the first choice treatment for diseases associated with excessive bone resorption, such as fragility fractures (due to postmenopausal-, male, glucocorticoid- and transplant-induced osteoporosis), Paget's disease of bone, and bone metastasis. Better understanding of BPs' effects on osteoblasts/osteocytes (e.g., preventing apoptosis) and differential distribution may further help explain anti-fracture benefit and bone quality effects. Lower affinity BPs (e.g., risedronate) may allow better access to osteocyte network. Effects of BPs on bone senescence, cancer cells apoptosis and prevention of cardiovascular calcifications may open new avenues for biogerontological research.

This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. IntroductionThere is compelling evidence suggesting that magnesium depletion may play a role in the pathophysiology of insulinresistance and/or altered glucose homeostasis in type 2 diabetes mellitus [1][2][3]. Magnesium is the second most abundant intracellular cation after potassium, and it is involved in a number of fundamental biochemical processes, comprising all ATP transferAbbreviations: ATP, adenosine triphosphate; BMI, body mass index; DBP, diastolic blood pressure; ESRD, end stage renal disease; FBG, fasting blood glucose; HbA1c, hemoglobin A1c; ISE, ion-selective electrode; NADPH, nicotinamide adenine dinucleotide phosphate-oxidase; NMR, nuclear magnetic resonance; Mg-tot, total serum magnesium; Mg-ion, extracellular free levels of magnesium; SBP, systolic blood pressure. ☆ None of the authors has any conflict of interest or financial support to disclose. ☆☆ There was no external funding for the study.