Magnesium in Aging, Health and Diseases

nutrients Review Magnesium in Aging, Health and Diseases Mario Barbagallo * , Nicola Veronese and Ligia J. Dominguez Geriatric Unit, Department of Medicine, University of Palermo, 90127 Palermo, Italy; [email protected] (N.V.); [email protected] (L.J.D.) * Correspondence: [email protected]; Tel.: +39-091-655-4828; Fax: +39-091-655-2952 Abstract: Several changes of magnesium (Mg) metabolism have been reported with aging, including diminished Mg intake, impaired intestinal Mg absorption and renal Mg wasting. Mild Mg deficits are generally asymptomatic and clinical signs are usually non-specific or absent. Asthenia, sleep disorders, hyperemotionality, and cognitive disorders are common in the elderly with mild Mg deficit, and may be often confused with age-related symptoms. Chronic Mg deficits increase the production of free radicals which have been implicated in the development of several chronic age- related disorders. Numerous human diseases have been associated with Mg deficits, including cardiovascular diseases, hypertension and stroke, cardio-metabolic syndrome and type 2 diabetes mellitus, airways constrictive syndromes and asthma, depression, stress-related conditions and psychiatric disorders, Alzheimer’s disease (AD) and other dementia syndromes, muscular diseases (muscle pain, chronic fatigue, and fibromyalgia), bone fragility, and cancer. Dietary Mg and/or Mg consumed in drinking water (generally more bioavailable than Mg contained in food) or in alternative Mg supplements should be taken into consideration in the correction of Mg deficits. Maintaining an optimal Mg balance all through life may help in the prevention of oxidative stress and chronic conditions associated with aging. This needs to be demonstrated by future studies. Keywords: magnesium; oxidative stress; diseases; dementia; diabetes; osteoporosis; aging; hypertension; health; longevity Citation: Barbagallo, M.; Veronese, N.; Dominguez, L.J. Magnesium in Aging, Health and Diseases. Nutrients 2021, 13, 463. 1. Introduction https://doi.org/10.3390/nu13020463 Magnesium ion (Mg) is the divalent intracellular cation most present in the human cell and the second cation after potassium (K). Mg atomic weight is 24.305 g/mol, and Academic Editor: Lutz Schomburg its atomic number is 12 (Table1). Mg has a crucial role in numerous biological processes, Received: 31 December 2020 including oxidative phosphorylation, energy production, glycolysis, protein and nucleic Accepted: 28 January 2021 Published: 30 January 2021 acid synthesis [1]. Mg plays a role in the mitochondrial synthesis of adenosine triphosphate (ATP) to form MgATP [2]. Cell signaling needs MgATP for protein phosphorylation and activation of cyclic adenosine monophosphate (cAMP), which is involved in a number Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in of biochemical processes [3]. Mg ions participate in the transport of other ions through published maps and institutional affil- cell membranes, in muscle contraction, and in controlling neuron excitability. Cellular Mg iations. homeostasis is linked to the cellular metabolism of other ions, i.e., K, sodium (Na), calcium (Ca), via Na+/K+/ATPase, Ca++ activated K channels, and other mechanisms [4]. Table 1. Characteristics of Ionic Mg. Copyright: © 2021 by the authors. • Element category: alkaline earth metal Licensee MDPI, Basel, Switzerland. • Atomic number: 12 This article is an open access article • Atomic weight: 24.305 g/mol distributed under the terms and • Valence: 2 conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ Mg has a key role for cellular homeostasis and organ functioning. Thus, Mg has a 4.0/). physiological role in controlling various key cellular activities and metabolic pathways, Nutrients 2021, 13, 463. https://doi.org/10.3390/nu13020463 https://www.mdpi.com/journal/nutrients Nutrients 2021, 13, x FOR PEER REVIEW 2 of 20 Nutrients 2021, 13, 463 2 of 20 Element category: alkaline earth metal Atomicincluding number: enzyme 12 substrate, structural and membrane functions [2,5]. Mg is a cofactor in Atomicover 600 weight: enzymatic 24.305 reactions g/mol and is required for the activity of protein kinases, glycolytic Valence:enzymes, 2 for all phosphorylation processes, and for all reactions that implicate ATP [2,5]. Mg ion has a mild Ca antagonist action and is involved in a number of structural functions In(multi-enzyme the last decades, complexes, the pathophysiological i.e., G-proteins, proteinsand clinical and importance nucleic acids of synthesis, Mg has been N-methyl- acknowledged,D-aspartic as acid well (NMDA) as the possible receptors, effects mitochondria, of Mg deficits polyribosomes, on several human etc.). diseases. In the last decades, the pathophysiological and clinical importance of Mg has been 2. Mg acknowledged,Metabolism and as R wellequirement as the possible effects of Mg deficits on several human diseases. The2. MgMg Metabolismcontent in the and human Requirement body is around 24–29 g of Mg, of which near 2/3 are deposited inThe bone Mg and content 1/3 in in the the cells. human Only body <1% is of around the total 24–29 Mg is g extracellular. of Mg, of which Mg near levels 2/3 are in the depositedserum range in bone between and 1/30.75 in and the 0.95 cells. mmol/L. Only <1% Serum of the Mg total levels Mg isin extracellular.healthy subjects Mg levels are veryin theconstant serum and range tightly between preserved 0.75 and within 0.95 this mmol/L. narrow Serum range Mg by levelsa dynamic in healthy balance subjects amongare Mg very intake, constant its intestinal and tightly absorption, preserved kidney within excretion, this narrow the bone range storage by a and dynamic the Mg balance requirementamong of Mg different intake, itstissues. intestinal Mg absorption absorption, is kidney increased excretion, under theconditions bone storage of Mg and lim- the Mg ited assumption.requirement If of Mg different deprivation tissues. persists, Mg absorption bone storages is increased would under help conditionsto preserve of serum Mg limited Mg levelsassumption. by replacing If Mg part deprivation of its content persists, in the bone extracellular storages wouldcompartment help to preserve[6] (Figure serum 1). Mg Serumlevels Mg levels by replacing are considered part of its low content if inferior in the than extracellular 0.75 mmol/L, compartment while frank [6] (Figurehypomag-1). Serum nesemiaMg is levels generally are considered considered low as ifserum inferior Mg than level 0.75 lower mmol/L, than 0.7 while mmol/L frank [1,2,7] hypomagnesemia. Total serumis Mg generally levels (MgT) considered are not as a serum sufficiently Mg level precise lower measure than 0.7 of mmol/L the body [ 1Mg,2,7 status;]. Total MgT serum Mg levels levelsare more (MgT) useful are notin epidemiological a sufficiently precise studies, measure but are of not the enough body Mg accurate status; MgTto detect levels are subclinicalmore Mg useful deficits in epidemiological on a single subject studies, [8]. This but is are because not enough serum accurate total Mg to levels detect do subclinical not accuratelyMg deficits mirror onintracellular a single subject concentrations, [8]. This is and because low serumintracellular total Mg Mg levels levels do generally not accurately precedemirror alterations intracellular of serum concentrations, Mg. It is thus andpossible low to intracellular have intracellular Mg levels and generally storage Mg precede depletionalterations with still of normal serum Mg. total It serum is thus Mg possible values to [6] have. intracellular and storage Mg depletion with still normal total serum Mg values [6]. Figure 1. Mg balance (arrows show most common sites of Mg depletion with aging), including daily amount of Mg intake and excretion. Total human body content of Mg is 24 to 29 g. In order to Figure 1. Mg balance (arrows show most common sites of Mg depletion with aging), including maintain Mg balance, a healthy person needs to consume around 5–7 mg/kg/day. Daily intestinal daily amount of Mg intake and excretion. Total human body content of Mg is 24 to 29 g. In order to maintainabsorption Mg balance, varies a from healthy 25 to person 60% of needs Mg intake. to consume In the around kidney, 5 80%–7 mg/kg/day. of circulating Daily Mg intesti- is filtered and nal absorptionabout 60% varies is reabsorbed from 25 to along 60% theof Mg kidney intake. tubule. In the This kidney results, 80% in aof net circulating excretion Mg of about is filtered 5 mmol/day. and aboutFecal 60% excretion is reabsorbed is about along 7.5 mmol/day. the kidney The tubule. intracellular This results compartment in a net excretion provides of theabout most 5 important mmol/day.Mg stores. Fecal excretion is about 7.5 mmol/day. The intracellular compartment provides the most important Mg stores. Optimal Mg requirement with food is considered to be 320 mg/day for women and Optimal420 mg/day Mg requirement for men, according with food to the is considered 2015–2020 Dietary to be 320 Guidelines mg/day for Americanswomen and [9 ], but 420 mg/higherday for requirements men, according may to be the needed 2015–2020 in some Dietary physiologic Guidelines conditions for Americans such as[9] pregnancy,, but higheraging, requirements or during may exercise be needed and in in some some ph pathologicalysiologic conditions conditions such (i.e., as infections,pregnancy, type 2 aging,diabetes or during mellitus exercise (T2DM), and in some etc.). pathological conditions (i.e., infections, type 2 diabetes mellitusMany (T2DM factors), etc.). may alter Mg balance: a high content in the diet of Na, Ca, protein, alcohol or caffeine, or the use of certain drugs (diuretics, e.g., furosemide; proton-pump inhibitors, e.g., Nutrients 2021, 13, 463 3 of 20 omeprazole, etc.). Mg absorption mainly occurs in the small intestine [10]. To maintain the balance, a healthy person needs to consume around 5–7 mg/kg/day (Table2).

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