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by",editors:[{id:"87201",title:"Dr.",name:"Maurizio",surname:"Balestrino",slug:"maurizio-balestrino",fullName:"Maurizio Balestrino"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},onlineFirst:{chapter:{type:"chapter",id:"73735",title:"Mineral Deficiencies: A Root Cause for Reduced Longevity in Mammals",doi:"10.5772/intechopen.94276",slug:"mineral-deficiencies-a-root-cause-for-reduced-longevity-in-mammals",body:'A regulated diet with all the constituents consumed in appropriate way maintains cell homeostasis and keeps the body under physiological state that are essential for cellular demands. A number of factor contribute to body function such as biomolecules, vitamins, minerals, and hormones etc.….of these minerals gain utmost importance due to availability inside the cell is low but shows a major effects even small change in concentration. Minerals perform wide variety of functions, which are essential for existence of organism. Some of them form integral components, some as cofactors, and some as essential components of enzymes. The existence of these minerals as part of enzymes helps to play a role in metabolism of molecules consumed through diet and maintain cell homeostasis. Some of the minerals acts in concert with aid of hormones according to their need in specific organelle. Minerals either in part or in combination with vitamins shows major functions required for the cell and their deficiencies shows adverse side effects although not hereditary. Minerals classified according to the need includes major (phosphorous (P), potassium (K), calcium (Ca), magnesium (Mg), sulphur (S)), minor/trace/rare (Boron (B), chlorine (Cl), chromium (Cr), fluoride (F), iodine (I), iron (Fe), manganese (Mn), molybdenum (Mo), nickel (Ni), selenium (Se), sodium (Na), vanadium (V) and zinc (Zn)). In this chapter a detailed explanation of selected minerals about their importance as a source requirement, uptake and transport mechanism, toxicity and tolerance mechanism, taken as means of measurement for determining their beneficial effects to study in detail about the specific role in metabolism their mechanism of action and deficiency diseases associated with reduced life span had described.
Decline of physiological functions leading to senescence of cells with arrest at G1 phase is characteristic feature of ageing [1]. At cellular level senescence was caused due to several factors such as oxidative stress, mitochondrial dysfunction, inflammation, autophagy deregulation, telomere shortening [2, 3]. Cells senesce either due to continuous replication or due to stress induction thereby activating p16, p53 pathways and phosphorylation of Rb protein [4] leading to inflammatory condition with high lysosomal β-galactosidase activity [5, 6, 7]. As cells continuously, divide chromosomes containing telomere with repeated nucleotides region gets shortened [8] leads to replicative senescence [9] and result in ageing. In humans, the repeated sequence at telomere region is TTAGGG [10]. Cells capable of replicating continuously express telomerase for replication of telomere ends of chromosome, which had tendency to reverse ageing process and used as targeted approach [2]. Increased ROS production due to stress apart from normal cellular homeostasis as a compensatory mechanism aggravates ageing phenomenon. Free-radical theory proposes ROS leads to oxidative damage and contributes to plays a role in the ageing process [11]. First call to increased ROS levels inside the cells is activation of survival pathways, which further leads to apoptosis due to failure of antioxidant system to defence against ROS that ultimately leads to cell death [12, 13]. Several factors were responsible for production of ROS that disturbs balance between cell survival and cell death through increased redox potential towards pro-inflammatory state and connects oxidative stress, inflammation and ageing [14, 15, 16]. The release of pro-inflammatory agents inside the senescent cells include TNF-α, IL-6, IL-1β [17] regulated by transcription factors such as AP-1, NFκB [18]. The activation of AP-1, NFκB requires kinases such as ERK, JNK, p38MAPK, PI3K [19] and leads to expression of target proteins such as MMP9, ICAM-1, iNOS, COX-2 [20, 21, 22]. Mitochondria apart from playing a role in oxidative phosphorylation system it also plays a role in apoptosis, metabolism, innate immunity and ageing [23, 24, 25]. Mitochondrial regulation occurs through PGC-1 (α & β) that responds to NAD+ levels inside the cell [26, 27] and in response to SIRT1 regulation occurs by HIF-1α independent of PGC-1 [28]. In ageing NAD+ levels decreases without loss of SIRT1 but downregulates it [29]. One of the contributing factor for cell survival under stress conditions is autophagy [30]. Autophagy is downregulated under nutrient rich conditions through mTOR protein [31] and stimulated through AMPK by phosphorylating mTOR (inactivation) ultimately activating ULK-1 [32]. Reports reveal autophagy deregulates due to overexpression of mTOR [33, 34] in ageing. Several Genetic events (mTOR, TGFβ), Molecular events (oxidative stress, autophagy) also contribute to ageing phenomenon. A summary of factors responsible for cellular ageing were shown in Figure 1.
Factors responsible for aging: Different factors enhances process of aging includes autophagy, oxidative stress, shortening of telomere, caloric restriction, proteostasis, inflammation, mitochondrial dysfunction and DNA damage.
Phosphorous is mostly present in meat, fish, eggs, and milk and dietary intake is 0.8-1.0 g/day. Phosphorus is essential for the formation of healthy bones, part of buffer system and component of DNA and RNA. Functions of phosphorous include formation of high-energy phosphates, nucleic acids, nucleotide coenzymes. Activation of enzymes require phosphate moiety and found in cell walls. Phosphorus deficiency include rickets, osteomalacia observed mostly in cases of malnutrition, anorexic individuals, or alcoholics. Symptoms are poor appetite, anxiety, and irritability. Phosphate absorption occurs in jejunum calcitriol, low pH favours their absorption while phytate reduces its absorption. Serum phosphate level is about 3-4 mg/dl and reduced in renal rickets, vitamin D deficient rickets and in diabetes mellitus. Phosphate excreted by kidney in the form of urine. Phosphate is mainly involved in mineralisation of the bone from chondrocytes and osteoblast. The process of mineralisation begins with hydroxyapatite formation from calcium (Ca + 2) and inorganic phosphate. Calcium incorporated through annexin calcium channel here as inorganic phosphate from type III sodium inorganic phosphate transporter and from PHOSPHO1. Hydroxyapatite penetrate the matrix vesicle and elongate due to tissue non-specific alkaline phosphatase (TNAP) and deposit in collagen fibre spaces [35]. The role of phosphorous in bone mineralisation shown in Figure 2a. Osteomalacia resulting from hypophosphatemia occurs through fibroblast growth factor signalling (FGF) [36] that links with ageing process [37]. Reduced phosphate levels inside the cell leads to increased FGF 23 levels in the serum and acts by inhibiting calcitriol, PTH, 1α-hydroxylase and stimulating 24-hydroxylase [38]. The signalling pathway connecting phosphorous deficiency and ageing shown in Figure 3.
Role of mineral elements in disease prevention. a: Role of phosphorous in bone mineralisation, b: Potassium involvement in muscle contraction, c: Calcium in bone calcification, d: Magnesium in protection of neuron degeneration, e: Sulphur in prevention of muscle pains and joint pains, f: Fluorine in preventation of dental caries, g: Iodine in thyroid hormones, h: Iron in haemoglobin synthesis, i: Sodium in heart function, j: Zinc in immunity.
Deficiency disease leads to aging through disturbed signalling pathway. Mineral deficiencies were shown in parenthesis. Ca: Calcium, I: Iodine, Mg: Magnesium, P: Phosphorous, Na: Sodium, S: Sulphur, Zn: Zinc, F: Fluorine, K: potassium, Fe: Iron. TSH: Thyroid stimulating hormone, Nrf 2-nucleoid erythroid receptor factor 2. FGF-fibroblast growth factor, SIRT1; Sirtuins 1, mTORC1: mammalian target of rapamycin complex 1, NFκB: Natural factor kappa beta, IL-6: interleukin 6, TGF-tumor growth factor, MAPK-mitogen activated protein kinase, Wnt-Wingless-related integration site.
Potassium is principal intracellular cation required daily about 3-4 g that is present majorly in banana, orange, potato, chicken, and liver. It helps regulate fluid balance, nerve signals and muscle contractions and beneficial aspects include reduction in blood pressure, water retention; prevention of kidney stones, osteoporosis, and protection against strokes. It functions to maintain intracellular osmotic balance, regulation of acid–base balance, required for transmission of nerve impulse, and necessary for biosynthesis of proteins. Plasma levels are 3.4-5 mEq/L absorbed through intestine excreted in form of urine. Deficiency diseases include muscle weakness, mental confusion. Potassium ion present on the cells as potassium ion channels and various types of potassium ion channels include ATP-sensitive K channels (KATP), voltage-dependent K channels (Kv), Ca2+ − and voltage-dependent K channels (BKCa), inward rectifier K channels (Kir), and tandem two-pore K channels (K2P) their activity varies in different types of diseases [39]. Potassium as known to play a role in Na + -K+ ATPase for effective muscle contraction [40] and motor regulation is by ATP driven potassium channels [41]. ATP driven potassium channel deficiency affected resting tension of skeletal muscle [42] deficiency of potassium ions alters sodium potassium pump of skeletal muscle and augments its contraction in ageing [43]. According to previous reports, high potassium levels depolarizes smooth muscle cells that opens up voltage gated calcium channels resulting in entry of calcium ions inside the cells thereby leading to activation of smooth muscle contraction [44] The role of potassium in muscle contraction shown in Figure 2b. It had reported that activation of mTORC1 signalling correlated with decline in muscle mass [45, 46] activated mTORC1induces oxidative stress that leads to protein degradation, autophagy and necrosis showing an aged phenotype [47]. The signalling pathway connecting potassium deficiency and ageing shown in Figure 3.
Biological availability of calcium is green leafy vegetables, nuts, seafood, cereals etc. Cow’s milk is rich source of calcium and required daily about 0.8-1.0 g/day. Calcium plays an important role in development of bones, muscle contraction, blood coagulation, nerve transmission, membrane integrity, activation of enzymes, intracellular messenger, contact inhibition, nerve excitability, skeletal muscle integrity and maintenance, and cardiac tone. Factors promoting calcium absorption include low pH, parathyroid hormone, vitamin D, lactose. Most of blood calcium is in plasma and ranges about 9-11 mg/dl. Factors regulating plasma calcium include calcitriol, parathyroid hormone, and calcitonin. Calcium excreted mostly through intestine and partly by kidneys. Deficiency of calcium leads to hypocalcemia and shown signs such as fragility of bone, muscle cramping, and dry skin. Deficiency diseases include rickets osteomalacia, osteoporosis. Evidences reveal that calcium is involved in bone calcification where osteoblasts secrete collagen as ground substance and polymerises it then osteoblast entrap osteoid and calcium salts precipitates as non-crystalline amorphous substance. Reabsorption and reprecipitation of hydroxyapatite crystals makes bone calcified. Existing reports evidence that stimulation of PGC-1α signalling regulate osteoporosis and ageing [48]. The role of calcium in osteoblast calcification shown in Figure 2c. Recent reports reveal that Wnt, MAPK, oestrogen pathways are targets for osteoporosis and ageing, it had shown that Wnt pathway responsible for production of sclerotin is dysregulated and MAPK pathway altered in osteoporosis [49]. The signalling pathway connecting calcium deficiency and ageing shown in Figure 3.
Sources of this mineral include milk, meat, fruits, and cereals. Biochemical functions include formation of bone, teeth, neuromuscular irritability, and cofactor for enzymes (kinases). Daily intake is 300-350 mg, serum concentration is 2-3 mg/dl and deficiency leads to convulsions, neuromuscular irritation, uraemia, and rickets. Magnesium absorption occurs in intestine alcohol inhibits it whereas parathormone enhances it. Causes of magnesium deficiency include alcohol abuse, poorly controlled diabetes, excessive or chronic vomiting and/or diarrhoea. Research on neurodegenerative diseases reveal magnesium had neuroprotective role by inhibiting influx of amyloid β from blood and promote its clearance [50] furthermore it attenuates impairment in long-term potentiation and impaired recruitment of synaptic proteins through activation of PI3K/Akt and inhibition of GSK3 β thereby reducing neuronal damage [51]. To date several reports indicate that Nrf-2 an antioxidant responsive protein plays a role in protection of cells from oxidative stress and essential for optimal activity inside the cell [52]. The role of magnesium in neuro degeneration shown in Figure 2d. Dysregulated Nrf-2 activity in neurodegenerative diseases linked to ageing [53, 54]. The signalling pathway connecting magnesium deficiency and ageing shown in Figure 3.
2.5 Sulphur (S): Egg white, chicken, fish, beef are major sources of sulphur. Daily intake is 14 mg for healthy adult and distributed in nails, hair, and skin. Sulphur plays a role as antioxidant, anti-inflammation, metal transport, free radical scavenging, protein stabilisation, xenobiotic detoxification, metabolism of lipids. Sulphur resides inside the body in organic form as methionine, cysteine, and cysteine functions as part of vitamins such as thiamine, biotin, and coenzyme A and excreted through oxidised form as taurine and cholic acid. Deficiency diseases are almost unknown. Although reports revealed that, sulphur containing amino acids in the form of methionine and cysteine forms creatinine, carnitine and coenzyme. Sulphur in the form of methylsulfonylmethane (MSM) acts to prevent muscle pains and joint pains through reduction of pro-inflammatory cytokines (NFkB, IL-1, IL-6, IL-8, TNF-α) [55, 56, 57] and decreased infiltration of immune cells by reducing inflamed synovial membrane [58, 59]. The role of sulphur in muscle pains and joint pains shown in Figure 2e. An essential for muscle functioning and deficiency leads to muscle impairment and aged phenotype. Aged muscle has altered Redox signalling [60, 61, 62] and exercised individuals in their lifetime had preserved enough muscle fitness comparable to younger ones [63] whereas NAD+ treatment [28] reverse these effects. Strenuous exercise result in muscle damage [64] and dysregulated redox response within the muscle increase in transient ROS/RNS. This clearly explains redox mechanisms operate with ageing and contraction of skeletal muscle can activate a number of transcription factors thereby affecting gene expression of specific cellular pathways. The signalling pathway connecting sulphur deficiency and ageing shown in Figure 3.
It occurs mostly in soil and water; dietary sources include leafy vegetables, pineapple, dry fruits, lemon, nuts, and berries and daily intake is <20 mg. It is ingested through diet and found higher quantities in hair, nails, bone whereas fat tissue being low [65]. It is absorbed into the intestine through boric acid and stored in tissues. The toxic effects of boron include DNA damage and repair and has effect on protein folding and stability. In infants, excess of boron leads to anaemia, seizures, erythema, dermatitis, cardiac problems [66, 67, 68]. Chronic exposure leads to disorders of brain, kidney, and testis (88). Boron determination utilises spectrophotometry [69], spectrofluorimetry [70], potentiometry [71], inductive coupled plasma atomic emission spectroscopy [72], and inductive coupled plasma mass spectrometry techniques [73]. Beneficial effects include reduction in sterility, osteoporosis, inflammation, coagulation, and cancer. Its application widely relays on food and medicinal sector.
Fluoride levels abundantly found in barley, rice, cassava, canned fruits and least in food grain, breast milk, beverages and daily intake is about 2 ppm. Fluoride levels in the environment is taken up either by food, water or inhaled by air, drugs and reach the digestive tract for metabolism and distributed inside the body bone, soft tissue, milk, tooth. The factors that influence the fluoride metabolism inside the body include acid–base disorders, hormones, physical activity, cardiac rhythm, and diet. Fluorine functions as prevention of dental caries, necessary for development of bones. The mechanism of action of fluoride inside the body involves inhibition of demineralisation of enamel. A small amount may substantially contribute to health benefits that include dental caries, decreases acid production. High levels leads to alterations in cell architecture, abnormalities in hepatic and renal systems. Fluoride poisoning inside the cells diagnosed by contraction of muscle, stiffness of body, failure of respiratory and cardiac systems. The methods for removing excess of fluorine done using coagulation-precipitation, electro coagulation, adsorption etc. Excreted through faeces, urine. Deficiency diseases include dental caries, osteoporosis. Fluoride helps in remineralisation, crystallisation and Fluoroapatite formation through enhancement of tooth and improves against acid resistance thereby preventing dental caries [74]. The role of fluorine in dental caries shown in Figure 2f. Reports reveal that klotho/KLF4 protein is involved in secretion of saliva from salivary gland and attenuation of KLF4 pathway thereby inactivating mTOR, AMPK, cyclin D1 that leads to dental caries [75]. The signalling pathway connecting fluoride deficiency and ageing shown in Figure 3.
It is abundant in seafood, iodised salt and daily intake is about 150-200 ug. It is component of thyroid hormones stored in the form of thyroglobulin and toxicity symptoms include thyrotoxicosis, goitre. Iodine is mainly absorbed through small intestine but also occurs through skin and lungs. Plasma level is 4-10 mg/dl. Iodine mainly excreted through kidney but also through skin, milk saliva and bile. Deficiency causes cretinism, goitre, and myxoedema. It is evident from existing reports that iodine uptake by thyroid cells occurs with the help of sodium iodine symporter and translocates to apical membrane fuses with thyroglobulin with the help of thyroperoxidase to form monoiododthyronine (MIT), diiodothyronine (DIT) in thyroid follicle cells. Coupling of MIT & DIT results in triiodothyronine (T3) & tetra iodothyronine (T4) which is internalised through endocytosis that releases free T3, T4 into the blood stream. Iodine deficiency leads to uptake of more thyroid-stimulating hormone (TSH) into thyroid cells for production of thyroid hormones (T3 & T4) which results in enlargement of thyroid gland to form goitre [76]. Age associated abnormality of thyroid gland is not consequence of ageing but result of thyroid autoantibodies that leads to age associated diseases [77]. The role of iodine in goitre shown in Figure 2g. Disturbed TSH signalling found in ageing individuals due to reduced release of TRH and less production of TSH thereby lowering the thyroid gland response to TSH with concomitant release of T3 and T4 [78] and enhances Ras activity that leads to increase of thyroid gland cell proliferation [79]. The signalling pathway connecting iodine deficiency and ageing shown in Figure 3.
Iron (non-heme) abundantly found in cereals, pulses, fruits, vegetables whereas heme is from poultry, fish and daily requirement is about 10-15 mg. Iron present in the form of heme transports oxygen, involved in electron transport chain, required for phagocytosis in form of peroxidase. Iron is absorbed in stomach and duodenum low pH, vitamin C enhances its absorption whereas phytate and oxalate interfere its absorption. Enterocytes absorb iron through metal transporter 1 protein and gets metabolised (heme) through heme oxygenase-1 [80, 81]. Inhibitors of iron absorption includes phytic acid [82], polyphenols [83], and calcium [84] whereas ascorbic acid is enhancer [85]. Iron is transported inside the body through circulating proteins namely transferrin, lactoferrin, ferritin, heme proteins [86]. Iron regulation inside the cells occurs by 2 mechanisms one is by binding of iron responsive elements (IRE) [87] to iron responsive proteins (IRP) and other by Hepcidin. Gene mutations of transferrin receptor 2, haemochromatosis, haemochromatosis type 2, hepcidin antimicrobial peptide (HAMP) [88] for impaired expression had observed. Iron storage inside the body is by ferritin [89] in liver, spleen, bone marrow [90]. Bodily iron is mostly excreted in form of blood through menstrual release and other forms includes skin and gastro intestinal tract [91] but not through urine. Iron deficiency results in depletion of iron and primary cause is low bioavailability of iron. It also occurs through pregnancy, menstruation, and pathologic conditions [92, 93]. Anaemia is the sign of iron deficiency [94]. Iron deficiency overcome by improvement in iron uptake and bioavailability, supplementation of iron with food and its fortification. Deficiency diseases include hypochromic microcytic anaemia. Reports evidence that iron (Fe+2) is absorbed by duodenal cells and binds with apoferritin to form ferritin which then binds to heme carrier protein (HCP) to form ferroportion (FPN). Ferroprotein is either stored in liver or transported in the blood, combines with transferrin in blood and reach erythrocytes that then binds to transferrin receptor and internalised into the cell and gets dissociated with the help of divalent metal carrier transporter 1 and performs functions such as erythropoiesis, cell metabolism, myoglobin production in muscles. Heme combines with myoglobin to form haemoglobin [59]. Recent reports reveal that PR domain zinc finger protein 8 (PRDM8) gene had a role in premature ageing of haematopoietic cells through DNA methylation that leads from aplastic anaemia (AA) patients independent of telomere attrition a haemoglobin disorder [95]. The role of iron in haemoglobin synthesis shown in Figure 2h. Reports also state that anaemia resulting from erythropoiesis of haematopoietic ageing of intrinsic altered microenvironment had upregulated IL-6, TGF-β signalling [96]. The signalling pathway connecting iron deficiency and ageing shown in Figure 3.
The daily intake of molybdenum was 75-250 ug and toxicity characterised by gout and joint pains. Molybdenum is present as cofactor for nitrate reductase, Xanthine oxidase and sulphite oxidase enzymes. Molybdenum cofactor biosynthesis occurs in steps formation of precursor Z from GTP, synthesis of molybbdeoprotein from precursor Z, addition of adenyl group to molybdoprotein and its insertion [97]. Molybdenum uptake inside the cells occurs with the help of ATP binding cassette transporters [98]. Molybdenum deficiency results in improper functioning of enzymes responsible for specific metabolic pathways in which they were involved and leads to metabolic diseases such as Xanthinuria, Hyperuricemia, and neurodegeneration. Deficiency diseases are almost unknown but some reports reveal its deficiency leads to chrons disease.
Abundantly found in common salt and other sources include leafy vegetables, milk, eggs, and nuts and daily intake is about 5-10 g. Absorbed as sodium ions and circulates inside the body in plasma and plasma levels were 135-145 mEq/L. It is cheif extra cellular cation regulates acid–base balance and involved in osmotic pressure. It is involved in activation & transmission of nerve impulse, absorption of biomolecules and aldosterone. High levels were observed in cushions disease and low levels were observed in addisons disease. Excreted from kidney in the form of sodium chloride through urine or as phosphate and other routes is by sweat. Deficiency diseases are almost unknown but reports reveal that higher risk of cardiovascular disease with low sodium intake [99]. Sodium inside the cells were present as sodium channels as (sodium-potassium ATPase, sodium-proton antiporter) the role of sodium in heart function is mostly presented by stimuation of aldosterone which enhaces its influx into the cell and activates inositol 1,4,5 tri phosphate (IP3) [100, 101]. Activated IP3 releases stored calcium from endoplasmic reticulum and makes excitation coupled to contraction for effective heart function [102]. The role of sodium in heart function shown in Figure 2i. SIRT1, mTORC1 regulate cell balance between cell growth and survival. Activation of SIRT1 along with PGC-1α, AMPK and inhibition of mTORC1 along with Akt act to prolong cell longevity and retard cardiac ageing. Autophagy underlies the activation of SIRT1/PGC-1 α/AMPK and inhibition of Akt/mTORC1 responsible for cardiac ageing. Chronic heart failure involves deficient autophagy phenomenon through hyperactivation of Akt/mTORC1 and suppression of SIRT1/PGC-1 α/AMPK pathway that finally leads to cardiac ageing [103, 104]. The signalling pathway connecting sodium deficiency and ageing shown in Figure 3.
Zinc mostly found in meat, cabbage, dates, mushrooms etc. and daily intake is 10-15 mg. Exposure of zinc is mainly by three ways inhalation, dermal exposure, oral exposure [105] and excess zinc shows symptoms such as abdominal pain, nausea, anaemia, gastrointestinal effects. Zinc plays an essential role as structural, catalytic, mild deficiency causes oligospermia, hyperammonemia [106]. Zinc is absorbed in duodenum phytate inhibits absorption whereas amino acids enhances its absorption. Oral uptake of zinc absorbs through small intestine and distributed in serum by binding to albumin, α-microglobulin, and transferrin [107]. Zinc homeostasis occurs mainly with the help of transport proteins namely Zinc importer (ZIP) and zinc transporter (ZnT) [108] which then binds to metallothionin, and sequester to other cell organelle. Beneficial aspects of zinc were antioxidant [109], antidepressant, antidiabetic [110], delayed wound healing, and anticancer [111]. Toxic effects of zinc observed when it crosses more than 100-300 mg/day typical symptoms include reduction of HDL and cholesterol levels, vomiting, lethargy, and fatigue. Serum zinc levels is about 100 mg/dl. Excretion of zinc occurs mainly by kidney, skin, and intestine. The role of zinc as immune protector well studied as anti-inflammatory and performs its action through reducing intracellular ROS by activating superoxide dismutase (SOD), NADPH oxidoreductase (NOX), metallothionin (MT) thereby suppressing inflammatory pathway (NFkB) and reduces it [112]. The role of zinc in immunity shown in Figure 2j. Zinc deficiency induces oxidative stress activates transcription factors NFkB, AP 1 through NFkB signalling in ageing process [113, 114]. The signalling pathway connecting zinc deficiency and ageing shown in Figure 3.
Minerals play an important role in daily life ranging from nuts to leafy vegetables. Minerals mainly function as cofactors along with enzymes to show their metabolic effect. Minerals form holoenzymes in metabolism of biomolecules and help in cellular vital process for cell survival. In their absence, the show some deficient metabolic effects and required in small amounts to function effectively. Intake varies from infants to adults, gender excess amounts shows hyper forms, and low amounts leads to hypo effects. Mineral deficiencies mostly show aged phenotype and age related diseases have mineral deficiencies. In their absence cell, survival pathways are mostly non-functional and leads to decreased metabolic function that is characterised by aged phenotype. Minerals classified mostly upon their requirement as major (phosphorous (P), potassium (K), calcium (Ca), magnesium (Mg), sulphur (S)), minor/trace/rare (Boron (B), chlorine (Cl), chromium (Cr), fluoride (F), iodine (I), iron (Fe), manganese (Mn), molybdenum (Mo), nickel (Ni), selenium (Se), sodium (Na), vanadium (V) and zinc (Zn)). A selected mineral with their function importance in mammals have been described in detail in which Phosphorous (P), Potassium (K), Calcium (Ca), Magnesium (Mg), Sulphur (S), Fluoride (F−), Iodide (I−), Iron (Fe), Sodium (Na), Zinc (Zn) along with mechanism of action and its diseased mechanism associated with ageing. Phosphorous is involved in bone mineralisation from osteocyte through hydroxyl apatite formation and deficiency leads to osteomalacia that related to ageing through increased fibroblast growth factor signalling. Potassium is involved in muscle contraction and its deficiency leads to muscle weakness and shows aged phenotype through enhanced mTORC1 signalling. Calcium is involved in bone calcification through hydroxyl apatite crystals its deficiency leads to bone disorders shows aged phenotype through dysregulated Wnt, MAPK pathway. Magnesium is involved in protection of neuron from degeneration through inhibition of GSK3β signalling and hyper activation of PI3K, Akt signalling and shows aged phenotype through dysregulated Nrf 2 pathway. Sulphur is involved in prevention of muscle pains and joint pains by reducing inflammation by scavenging free radicals its deficiency leads to muscle fatigue shows aged phenotype through reduced redox signalling. Fluorine is involved protection of enamel layer by remineralisation, crystallisation of dentine and enhancement in acid resistance its deficiency leads to dental caries which is also an aged phenotype due to disturbed KLF4pathway. Iodine is necessary for thyroid gland for production of thyroid hormones deficiency of it leads to goitre that is characterised by thyroid gland enlargement seen mostly in aged people or people taking iodine deficient diets that occurs through reduced TSH signalling. Iron is necessary for body for haemoglobin synthesis for oxygen transport and its deficiency leads to anaemia an aged phenotype occurs through enhancement in IL-6, TGFβ signalling. Sodium shows its effect by action of aldosterone on muscle cells and helps in heart function deficiency leads to heart diseases an aged phenotype occurs through increased SIRT1, mTORC1 signalling. Zinc well known for immune defence through inhibition of NFκB signalling deficiency leads to reduced immunity through enhancement of this signalling. A summary of different minerals and their mechanism of action along with their associated signalling pathway with ageing had described in Table 1.
Mineral | Physiological function | Mechanism of action | Deficiency disease | Signalling pathway associated with ageing |
---|---|---|---|---|
Phosphorous (P) | Formation of high energy phosphates, nucleic acids, nucleotide coenzymes | Bone mineralisation through hydroxyapatite formation [35] | Osteomalacia | FGF signalling [36, 37] |
Potassium (K) | Chief cation of intracellular fluid, osmotic balance, muscle function | Contraction of smooth muscle cell [44] | Muscle weakness, mental retardation | mTORC1 signalling [47] |
Calcium (Ca) | Development of bones, muscle contraction, blood coagulation, nerve transmission, intracellular messenger etc. | Bone calcification through formation of hydroxyl apatite crystals | Rickets, Osteoporosis, Osteopetrosis (marble bone disease) | Wnt, MAPK pathway [49] |
Magnesium (Mg) | Constituent of bones, cofactor for kinases | Protects neuronal cell death by activating PI3K/Akt signalling [51] | Neuromuscular weakness, muscle irritation | Nrf 2 pathway [53, 54] |
Sulphur (S) | Constituent of vitamins, heparin, chondroitin sulphate | Reduces muscle pain and body pain [55, 56, 57] | Muscle fatigue, convulsions | Redox signalling [60, 61, 62] |
Fluorine (F) | Formation of bones and teeth | Prevents dental caries by remineralisation of enamel and improving acid resistance [74] | Dental caries | KLF 4 pathway [75] |
Iodine (I) | Constituent of thyroxine, triiodothyronine | Prevents thyroid enlargement through T3 &T4 [76] | Goitre, Myxoedema | TSH signalling [78] |
Iron (Fe) | Transports oxygen in constituent of heme | Haemoglobin formation through erythropoiesis [59] | Hypochromic microcytic anaemia | TGF-β signalling [96] |
Sodium (Na) | Chief cation of extracellular fluid, osmotic balance, acid–base balance, nerve function | Regulates heart function through IP3signaling by aldosterone [100, 101, 102] | Heart disease | SIRT1, mTORC1 signalling [103, 104] |
Zinc (Zn) | Cofactor for alcohol dehydrogenase, carbonic anhydrase, lactate dehydrogenase | Reduces intracellular ROS by activating SOD, NOX, MT [112] | Growth retardation, hypogonadism, decreased immunity | NFkB signalling [113, 114] |
Summary of mineral elements mechanism of action and association with longevity.
Abbreviations: FGF-fibroblast growth factor, SOD-superoxide dismutase, NOX-NADPH oxidase, MT-metallothionin, T3-tri iodothyronine, T4-tetra iodothyronine, PI3K-Phosphatidyl inositol 3 kinase, MAPK-mitogen activated protein kinase, Wnt-Wingless-related integration site, Nrf 2-nucleoid erythroid receptor factor 2, TSH-thyroid stimulating hormone, TGF-tumour growth factor, SIRT 1-sirutin1, mTORC1-mammalian target of rapamycin complex 1, NFkB-natural factor kappa beta.
calcium iodine magnesium phosphorous sodium sulphur zinc Fluorine potassium iron thyroid stimulating hormone nucleoid erythroid receptor factor fibroblast growth factor sirtuins mammalian target of rapamycin complex natural factor kappa beta interleukin tumour growth factor mitogen activated protein kinase Wingless-related integration site fibroblast growth factor superoxide dismutase NADPH oxidase metallothionin tri iodothyronine tetra iodothyronine phosphatidyl inositol 3 kinase zinc importer zinc transporter glycogen synthase kinase 3β reactive oxygen species reactive nitrogen species high density lipoprotein peroxisome proliferator-activated receptor gamma coactivator inositol 1,4,5 tri phosphate adenosine tri phosphatase guanosine triphosphate PR domain zinc finger protein 8 aplastic anaemia heme carrier protein ferroportion iron responsive proteins iron responsive elements hepcidin antimicrobial peptide monoiododthyronine diiodothyronine thyroid-stimulating hormone adenosine monophosphate kinase deoxyribose nucleic acid ribose nucleic acid nicotinamide adenosine dinucleotide tumour necrosis factor methylsulfonylmethane fibroblast growth factor signalling parathormone tissue non-specific alkaline phosphatase Unc-51 like autophagy activating kinase (ULK1/2) matrix metallo proteinase inter cellular adhesion molecule induced nitric oxide synthase cyclooxygenase recommended dietary allowance
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\n\nMy order has not arrived, what do I do?
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At this point, we relied on the firstly discovered ability of the DNA base mispairs to tautomerize via the sequential intrapair proton transfer and highly stable, highly polar, zwitterionic transition states, accompanied by a significant shifting of the base mispairs toward DNA minor or major grooves. These tautomeric transitions are characterized by a change in geometry—from wobble to Watson-Crick and vice versa—of the purine·pyrimidine (A·T, G·C, G·T and A·C), purine·purine (A·A, A·G and G·G) and pyrimidine·pyrimidine (С·С, С·T and Т·Т) DNA base mispairs. Reported results allow us to explain, on one side, the origin of the mutagenic tautomers at the separation of the DNA strands before replication and, on the other side, how DNA base mispairs adapt to enzymatically competent size in the tight recognition pocket of the high-fidelity DNA polymerase.",book:{id:"6684",slug:"mitochondrial-dna-new-insights",title:"Mitochondrial DNA",fullTitle:"Mitochondrial DNA - New Insights"},signatures:"Ol’ha O. Brovarets’ and Dmytro M. 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The primary mechanism responsible for DOX’s cardiospecific toxicity remains unidentified so far; however, mitochondrial dysfunction induced by DOX is now considered one of the leading reasons for DOX’s toxicities and undesired side effects. Mitochondrial reactive oxygen production in the heart is a significant contributor to developing mitochondrial dysfunction-exposed DOX based on a variety of evidence. The objective of this review chapter is to critically evaluate and highlight the role of mitochondria in the development of DOX-induced cardiotoxicity.",book:{id:"6060",slug:"mitochondrial-diseases",title:"Mitochondrial Diseases",fullTitle:"Mitochondrial Diseases"},signatures:"Celal Guven, Yusuf Sevgiler and Eylem Taskin",authors:[{id:"192567",title:"Prof.",name:"Eylem",middleName:null,surname:"Taskin",slug:"eylem-taskin",fullName:"Eylem Taskin"},{id:"195229",title:"Dr.",name:"Celal",middleName:null,surname:"Guven",slug:"celal-guven",fullName:"Celal Guven"},{id:"206996",title:"Prof.",name:"Yusuf",middleName:null,surname:"Sevgiler",slug:"yusuf-sevgiler",fullName:"Yusuf Sevgiler"}]},{id:"63421",doi:"10.5772/intechopen.80871",title:"Directed Mutations Recode Mitochondrial Genes: From Regular to Stopless Genetic Codes",slug:"directed-mutations-recode-mitochondrial-genes-from-regular-to-stopless-genetic-codes",totalDownloads:919,totalCrossrefCites:7,totalDimensionsCites:10,abstract:"Mitochondrial genetic codes evolve as side effects of stop codon ambiguity: suppressor tRNAs with anticodons translating stops transform genetic codes to stopless genetic codes. This produces peptides from frames other than regular ORFs, potentially increasing protein numbers coded by single sequences. Previous descriptions of marine turtle Olive Ridley mitogenomes imply directed stop-depletion of noncoding +1 gene frames, stop-creation recodes regular ORFs to stopless genetic codes. In this analysis, directed stop codon depletion in usually noncoding gene frames of the spiraling whitefly Aleurodicus dispersusʼ mitogenome produces new ORFs, introduces stops in regular ORFs, and apparently increases coding redundancy between different gene frames. Directed stop codon mutations switch between peptides coded by regular and stopless genetic codes. This process seems opposite to directed stop creation in HIV ORFs within genomes of immunized elite HIV controllers. Unknown DNA replication/edition mechanisms probably direct stop creation/depletion beyond natural selection on stops. Switches between genetic codes regulate translation of different gene frames.",book:{id:"6684",slug:"mitochondrial-dna-new-insights",title:"Mitochondrial DNA",fullTitle:"Mitochondrial DNA - New Insights"},signatures:"Hervé Seligmann",authors:[{id:"118814",title:"Dr.",name:"Herve",middleName:null,surname:"Seligmann",slug:"herve-seligmann",fullName:"Herve Seligmann"}]},{id:"68488",doi:"10.5772/intechopen.88445",title:"Mitochondrial Dysfunction as a Key Event during Aging: From Synaptic Failure to Memory Loss",slug:"mitochondrial-dysfunction-as-a-key-event-during-aging-from-synaptic-failure-to-memory-loss",totalDownloads:1204,totalCrossrefCites:6,totalDimensionsCites:10,abstract:"Mitochondria are important cellular organelles with key regulatory functions in energy production, oxidative balance, and calcium homeostasis. This is especially important in the brain, since neurons require a large number of functional mitochondria to supply their high energy requirement, mainly for synaptic processes. A decrease in the activity and quality of mitochondria in the brain, particularly in the hippocampus, is associated with normal aging and a large number of neurodegenerative diseases compromising memory function. Although synaptic and cognitive dysfunction is multifactorial, growing evidence demonstrates that mitochondria play a key role in these processes and suggests that maintaining mitochondrial function could prevent these age-dependent alterations. In this chapter, we will discuss the hippocampal mitochondrial dysfunction present in aging and how these defects promote age-associated synaptic damage and cognitive impairment. We will summarize evidence that shows how neurodegeneration can be accelerated or attenuated during aging by modulating mitochondrial function.",book:{id:"7850",slug:"mitochondria-and-brain-disorders",title:"Mitochondria and Brain Disorders",fullTitle:"Mitochondria and Brain Disorders"},signatures:"Claudia Jara, Angie K. Torres, Margrethe A. Olesen and Cheril Tapia-Rojas",authors:[{id:"183873",title:"Dr.",name:"Claudia",middleName:null,surname:"Jara",slug:"claudia-jara",fullName:"Claudia Jara"},{id:"299224",title:"Dr.",name:"Cheril",middleName:null,surname:"Tapia-Rojas",slug:"cheril-tapia-rojas",fullName:"Cheril Tapia-Rojas"},{id:"299227",title:"Ms.",name:"Angie K.",middleName:null,surname:"Torres",slug:"angie-k.-torres",fullName:"Angie K. Torres"},{id:"299230",title:"Ms.",name:"Margrethe",middleName:null,surname:"A. Olesen",slug:"margrethe-a.-olesen",fullName:"Margrethe A. Olesen"}]},{id:"63439",doi:"10.5772/intechopen.80805",title:"Swinger RNAs in the Human Mitochondrial Transcriptome",slug:"swinger-rnas-in-the-human-mitochondrial-transcriptome",totalDownloads:848,totalCrossrefCites:3,totalDimensionsCites:8,abstract:"Transcriptomes include coding and non-coding RNAs and RNA fragments with no apparent homology to parent genomes. Non-canonical transcriptions systematically transforming template DNA sequences along precise rules explain some transcripts. Among these systematic transformations, 23 systematic exchanges between nucleotides, i.e. 9 symmetric (X ↔ Y, e.g. C ↔ T) and 14 asymmetric (X → Y → Z → X, e.g. A → T → G → A) exchanges. Here, comparisons between mitochondrial swinger RNAs previously detected in a complete human transcriptome dataset (including cytosolic RNAs) and swinger RNAs detected in purified mitochondrial transcriptomic data (not including cytosolic RNAs) show high reproducibility and exclude cytosolic contaminations. These results based on next-generation sequencing Illumina technology confirm detections of mitochondrial swinger RNAs in GenBank’s EST database sequenced by the classical Sanger method, assessing the existence of swinger polymerizations.",book:{id:"6684",slug:"mitochondrial-dna-new-insights",title:"Mitochondrial DNA",fullTitle:"Mitochondrial DNA - New Insights"},signatures:"Ganesh Warthi and Hervé Seligmann",authors:[{id:"230498",title:"Dr.",name:"Ganesh",middleName:null,surname:"Warthi",slug:"ganesh-warthi",fullName:"Ganesh Warthi"},{id:"239210",title:"Prof.",name:"Hervé",middleName:null,surname:"Seligmann",slug:"herve-seligmann",fullName:"Hervé Seligmann"}]}],mostDownloadedChaptersLast30Days:[{id:"63034",title:"Mitochondrial Dysfunction Associated with Doxorubicin",slug:"mitochondrial-dysfunction-associated-with-doxorubicin",totalDownloads:1638,totalCrossrefCites:6,totalDimensionsCites:13,abstract:"Cancer prevalence is scaling up each year. Anthracycline groups are still the best chemotherapeutic agent. The most popular anticancer drug in the group is doxorubicin (DOX). Unfortunately, DOX has potent toxicity on noncancerous tissues, e.g., heart, kidneys, etc. However, it is well documented that the severest toxicity of the drug affects heart tissue. Of course, some reasons have been suggested why and/or how the heart is so vulnerable to toxicity. The primary mechanism responsible for DOX’s cardiospecific toxicity remains unidentified so far; however, mitochondrial dysfunction induced by DOX is now considered one of the leading reasons for DOX’s toxicities and undesired side effects. Mitochondrial reactive oxygen production in the heart is a significant contributor to developing mitochondrial dysfunction-exposed DOX based on a variety of evidence. The objective of this review chapter is to critically evaluate and highlight the role of mitochondria in the development of DOX-induced cardiotoxicity.",book:{id:"6060",slug:"mitochondrial-diseases",title:"Mitochondrial Diseases",fullTitle:"Mitochondrial Diseases"},signatures:"Celal Guven, Yusuf Sevgiler and Eylem Taskin",authors:[{id:"192567",title:"Prof.",name:"Eylem",middleName:null,surname:"Taskin",slug:"eylem-taskin",fullName:"Eylem Taskin"},{id:"195229",title:"Dr.",name:"Celal",middleName:null,surname:"Guven",slug:"celal-guven",fullName:"Celal Guven"},{id:"206996",title:"Prof.",name:"Yusuf",middleName:null,surname:"Sevgiler",slug:"yusuf-sevgiler",fullName:"Yusuf Sevgiler"}]},{id:"68488",title:"Mitochondrial Dysfunction as a Key Event during Aging: From Synaptic Failure to Memory Loss",slug:"mitochondrial-dysfunction-as-a-key-event-during-aging-from-synaptic-failure-to-memory-loss",totalDownloads:1204,totalCrossrefCites:6,totalDimensionsCites:10,abstract:"Mitochondria are important cellular organelles with key regulatory functions in energy production, oxidative balance, and calcium homeostasis. This is especially important in the brain, since neurons require a large number of functional mitochondria to supply their high energy requirement, mainly for synaptic processes. A decrease in the activity and quality of mitochondria in the brain, particularly in the hippocampus, is associated with normal aging and a large number of neurodegenerative diseases compromising memory function. Although synaptic and cognitive dysfunction is multifactorial, growing evidence demonstrates that mitochondria play a key role in these processes and suggests that maintaining mitochondrial function could prevent these age-dependent alterations. In this chapter, we will discuss the hippocampal mitochondrial dysfunction present in aging and how these defects promote age-associated synaptic damage and cognitive impairment. We will summarize evidence that shows how neurodegeneration can be accelerated or attenuated during aging by modulating mitochondrial function.",book:{id:"7850",slug:"mitochondria-and-brain-disorders",title:"Mitochondria and Brain Disorders",fullTitle:"Mitochondria and Brain Disorders"},signatures:"Claudia Jara, Angie K. Torres, Margrethe A. Olesen and Cheril Tapia-Rojas",authors:[{id:"183873",title:"Dr.",name:"Claudia",middleName:null,surname:"Jara",slug:"claudia-jara",fullName:"Claudia Jara"},{id:"299224",title:"Dr.",name:"Cheril",middleName:null,surname:"Tapia-Rojas",slug:"cheril-tapia-rojas",fullName:"Cheril Tapia-Rojas"},{id:"299227",title:"Ms.",name:"Angie K.",middleName:null,surname:"Torres",slug:"angie-k.-torres",fullName:"Angie K. Torres"},{id:"299230",title:"Ms.",name:"Margrethe",middleName:null,surname:"A. Olesen",slug:"margrethe-a.-olesen",fullName:"Margrethe A. Olesen"}]},{id:"62948",title:"Pyrethroid Insecticides as the Mitochondrial Dysfunction Inducers",slug:"pyrethroid-insecticides-as-the-mitochondrial-dysfunction-inducers",totalDownloads:1434,totalCrossrefCites:3,totalDimensionsCites:7,abstract:"Pyrethroids are used to decrease vector-based health concerns and to increase field yield against agricultural pests. Their metabolism is a concern to disrupt a cell’s homeostatic machinery via reactive oxygen species (ROS) production. They interact with lipid membranes to damage the fine balance between membrane lipids and membrane proteins, especially mitochondrial substrate transporters and electron carriers. Pyrethroids cause a shift in the metabolic energy production strategy, resulting in ROS production and intracellular lipid deposition. The change of open/closed conformation of some mitochondrial membrane proteins increases the vulnerability of mitochondria to Ca2+ ions. Membrane lipid fluidity change is also a concern because of permeability to the substrates and ions to produce energy and other substrates necessary for the cell. Pyrethroids can change the Ca2+ signaling and its interaction with ROS signals via disruption of the fine balance between endoplasmic reticulum and mitochondria. They can disrupt the mitochondrial DNA (mtDNA) via their hydrophobic nature or their ROS production capacity. In conclusion, mitochondria are the center of pyrethroid toxicity, and dysfunction of this organelle via pyrethroid toxicity plays an important role in the fate of cell. Their lipophilic and pro-oxidative nature together with Ca2+ homeostasis plays a synergistic role in this mitochondrial effect.",book:{id:"6060",slug:"mitochondrial-diseases",title:"Mitochondrial Diseases",fullTitle:"Mitochondrial Diseases"},signatures:"Celal Guven, Yusuf Sevgiler and Eylem Taskin",authors:[{id:"192567",title:"Prof.",name:"Eylem",middleName:null,surname:"Taskin",slug:"eylem-taskin",fullName:"Eylem Taskin"}]},{id:"58177",title:"Mitochondria and Heart Disease",slug:"mitochondria-and-heart-disease",totalDownloads:1265,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Mitochondria play a key role in the normal functioning of the heart and in the pathogenesis and development of various types of heart disease. In addition, specific mitochondrial cardiomyopathies due to mutations in mitochondrial DNA have been identified. Increasing studies demonstrate that mitochondrial function has emerged as a therapeutic target in heart disease. This chapter addresses the recent studies of the role and the mechanism of mitochondria in the development of heart disease, and the progress in clinical diagnosis and treatments on a mitochondrial basis. Consequently, the aim of this chapter is to outline current knowledge about mitochondria in the heart disease.",book:{id:"6060",slug:"mitochondrial-diseases",title:"Mitochondrial Diseases",fullTitle:"Mitochondrial Diseases"},signatures:"Shaunrick Stoll, Christiana Leimena and Hongyu Qiu",authors:[{id:"207057",title:"Dr.",name:"Hongyu",middleName:null,surname:"Qiu",slug:"hongyu-qiu",fullName:"Hongyu Qiu"},{id:"217395",title:"Mr.",name:"Shaunrick",middleName:null,surname:"Stoll",slug:"shaunrick-stoll",fullName:"Shaunrick Stoll"},{id:"217396",title:"Dr.",name:"Christiana",middleName:null,surname:"Leimena",slug:"christiana-leimena",fullName:"Christiana Leimena"}]},{id:"58886",title:"Modulation of Mitochondria During Viral Infections",slug:"modulation-of-mitochondria-during-viral-infections",totalDownloads:1741,totalCrossrefCites:5,totalDimensionsCites:6,abstract:"Mitochondria are organelles critical for cell survival because they produce ATP and modulate programmed cell death (PCD) pathways. PCD pathways are important in many clinical disorders, such as ischemia/reperfusion injuries, trauma, and toxic/metabolic syndromes, as well as in chronic neurodegenerative conditions, such as amyotrophic lateral sclerosis, Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Moreover, many viruses and other pathogens target the mitochondria. Viruses induce the production of various proteins in their hosts that have proapoptotic and anti-apoptotic activities, depending on the cellular environment. More specifically, many viruses that target mitochondria regulate the balance between the anti- and proapoptotic Bcl-2 family proteins and thereby increase their own survival within the host cell. Recent studies indicated that mitochondria centralize several critical innate immune responses based on the presence of several important signaling proteins within the mitochondria: mitochondrial antiviral signaling (MAVS), stimulation of interferon genes (STING), and NLR family member X1. Therefore, mitochondria are not only vital because they regulate cell survival and death but also they have broad roles in the control of cell functions following pathogen invasion. This chapter highlights the tight interplay between viral infection and mitochondria.",book:{id:"6060",slug:"mitochondrial-diseases",title:"Mitochondrial Diseases",fullTitle:"Mitochondrial Diseases"},signatures:"Latif Reshi, Hao-Ven Wang and Jiann-Ruey Hong",authors:[{id:"66487",title:"Prof.",name:"Jiann",middleName:"Ruey",surname:"Hong",slug:"jiann-hong",fullName:"Jiann Hong"},{id:"206951",title:"Dr.",name:"Lateef",middleName:null,surname:"Reshi",slug:"lateef-reshi",fullName:"Lateef Reshi"},{id:"213164",title:"Dr.",name:"Hao -Ven",middleName:null,surname:"Wang",slug:"hao-ven-wang",fullName:"Hao -Ven Wang"}]}],onlineFirstChaptersFilter:{topicId:"1049",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:287,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343",scope:"Biomedical Engineering is one of the fastest-growing interdisciplinary branches of science and industry. The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. Nowadays, all medical imaging devices, medical instruments, or new laboratory techniques result from the cooperation of specialists in various fields. The series of Biomedical Engineering books covers such areas of knowledge as chemistry, physics, electronics, medicine, and biology. This series is intended for doctors, engineers, and scientists involved in biomedical engineering or those wanting to start working in this field.",coverUrl:"https://cdn.intechopen.com/series/covers/7.jpg",latestPublicationDate:"May 13th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:12,editor:{id:"50150",title:"Prof.",name:"Robert",middleName:null,surname:"Koprowski",slug:"robert-koprowski",fullName:"Robert Koprowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTYNQA4/Profile_Picture_1630478535317",biography:"Robert Koprowski, MD (1997), PhD (2003), Habilitation (2015), is an employee of the University of Silesia, Poland, Institute of Computer Science, Department of Biomedical Computer Systems. For 20 years, he has studied the analysis and processing of biomedical images, emphasizing the full automation of measurement for a large inter-individual variability of patients. Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"7",title:"Bioinformatics and Medical Informatics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",isOpenForSubmission:!0,editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",slug:"slawomir-wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",biography:"Professor Sławomir Wilczyński, Head of the Chair of Department of Basic Biomedical Sciences, Faculty of Pharmaceutical Sciences, Medical University of Silesia in Katowice, Poland. His research interests are focused on modern imaging methods used in medicine and pharmacy, including in particular hyperspectral imaging, dynamic thermovision analysis, high-resolution ultrasound, as well as other techniques such as EPR, NMR and hemispheric directional reflectance. Author of over 100 scientific works, patents and industrial designs. Expert of the Polish National Center for Research and Development, Member of the Investment Committee in the Bridge Alfa NCBiR program, expert of the Polish Ministry of Funds and Regional Policy, Polish Medical Research Agency. Editor-in-chief of the journal in the field of aesthetic medicine and dermatology - Aesthetica.",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},{id:"8",title:"Bioinspired Technology and Biomechanics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",isOpenForSubmission:!0,editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",slug:"adriano-andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",biography:"Dr. Adriano de Oliveira Andrade graduated in Electrical Engineering at the Federal University of Goiás (Brazil) in 1997. He received his MSc and PhD in Biomedical Engineering respectively from the Federal University of Uberlândia (UFU, Brazil) in 2000 and from the University of Reading (UK) in 2005. He completed a one-year Post-Doctoral Fellowship awarded by the DFAIT (Foreign Affairs and International Trade Canada) at the Institute of Biomedical Engineering of the University of New Brunswick (Canada) in 2010. Currently, he is Professor in the Faculty of Electrical Engineering (UFU). He has authored and co-authored more than 200 peer-reviewed publications in Biomedical Engineering. He has been a researcher of The National Council for Scientific and Technological Development (CNPq-Brazil) since 2009. He has served as an ad-hoc consultant for CNPq, CAPES (Coordination for the Improvement of Higher Education Personnel), FINEP (Brazilian Innovation Agency), and other funding bodies on several occasions. He was the Secretary of the Brazilian Society of Biomedical Engineering (SBEB) from 2015 to 2016, President of SBEB (2017-2018) and Vice-President of SBEB (2019-2020). He was the head of the undergraduate program in Biomedical Engineering of the Federal University of Uberlândia (2015 - June/2019) and the head of the Centre for Innovation and Technology Assessment in Health (NIATS/UFU) since 2010. He is the head of the Postgraduate Program in Biomedical Engineering (UFU, July/2019 - to date). He was the secretary of the Parkinson's Disease Association of Uberlândia (2018-2019). Dr. Andrade's primary area of research is focused towards getting information from the neuromuscular system to understand its strategies of organization, adaptation and controlling in the context of motor neuron diseases. His research interests include Biomedical Signal Processing and Modelling, Assistive Technology, Rehabilitation Engineering, Neuroengineering and Parkinson's Disease.",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",isOpenForSubmission:!0,editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",slug:"luis-villarreal-gomez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",biography:"Dr. Luis Villarreal is a research professor from the Facultad de Ciencias de la Ingeniería y Tecnología, Universidad Autónoma de Baja California, Tijuana, Baja California, México. Dr. Villarreal is the editor in chief and founder of the Revista de Ciencias Tecnológicas (RECIT) (https://recit.uabc.mx/) and is a member of several editorial and reviewer boards for numerous international journals. He has published more than thirty international papers and reviewed more than ninety-two manuscripts. His research interests include biomaterials, nanomaterials, bioengineering, biosensors, drug delivery systems, and tissue engineering.",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:17,paginationItems:[{id:"81751",title:"NanoBioSensors: From Electrochemical Sensors Improvement to Theranostic Applications",doi:"10.5772/intechopen.102552",signatures:"Anielle C.A. Silva, Eliete A. Alvin, Lais S. de Jesus, Caio C.L. de França, Marílya P.G. da Silva, Samaysa L. Lins, Diógenes Meneses, Marcela R. Lemes, Rhanoica O. Guerra, Marcos V. da Silva, Carlo J.F. de Oliveira, Virmondes Rodrigues Junior, Renata M. Etchebehere, Fabiane C. de Abreu, Bruno G. Lucca, Sanívia A.L. Pereira, Rodrigo C. Rosa and Noelio O. Dantas",slug:"nanobiosensors-from-electrochemical-sensors-improvement-to-theranostic-applications",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Biosignal Processing",coverURL:"https://cdn.intechopen.com/books/images_new/11153.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"81766",title:"Evolution of Organoids in Oncology",doi:"10.5772/intechopen.104251",signatures:"Allen Thayakumar Basanthakumar, Janitha Chandrasekhar Darlybai and Jyothsna Ganesh",slug:"evolution-of-organoids-in-oncology",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Organoids",coverURL:"https://cdn.intechopen.com/books/images_new/11430.jpg",subseries:null}},{id:"81678",title:"Developmental Studies on Practical Enzymatic Phosphate Ion Biosensors and Microbial BOD Biosensors, and New Insights into the Future Perspectives of These Biosensor Fields",doi:"10.5772/intechopen.104377",signatures:"Hideaki Nakamura",slug:"developmental-studies-on-practical-enzymatic-phosphate-ion-biosensors-and-microbial-bod-biosensors-a",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:[{name:"Hideaki",surname:"Nakamura"}],book:{title:"Biosignal Processing",coverURL:"https://cdn.intechopen.com/books/images_new/11153.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"81547",title:"Organoids and Commercialization",doi:"10.5772/intechopen.104706",signatures:"Anubhab Mukherjee, Aprajita Sinha, Maheshree Maibam, Bharti Bisht and Manash K. Paul",slug:"organoids-and-commercialization",totalDownloads:32,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Organoids",coverURL:"https://cdn.intechopen.com/books/images_new/11430.jpg",subseries:null}}]},overviewPagePublishedBooks:{paginationCount:12,paginationItems:[{type:"book",id:"6692",title:"Medical and Biological Image Analysis",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6692.jpg",slug:"medical-and-biological-image-analysis",publishedDate:"July 4th 2018",editedByType:"Edited by",bookSignature:"Robert Koprowski",hash:"e75f234a0fc1988d9816a94e4c724deb",volumeInSeries:1,fullTitle:"Medical and Biological Image Analysis",editors:[{id:"50150",title:"Prof.",name:"Robert",middleName:null,surname:"Koprowski",slug:"robert-koprowski",fullName:"Robert Koprowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTYNQA4/Profile_Picture_1630478535317",biography:"Robert Koprowski, MD (1997), PhD (2003), Habilitation (2015), is an employee of the University of Silesia, Poland, Institute of Computer Science, Department of Biomedical Computer Systems. For 20 years, he has studied the analysis and processing of biomedical images, emphasizing the full automation of measurement for a large inter-individual variability of patients. Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}}]},{type:"book",id:"7218",title:"OCT",subtitle:"Applications in Ophthalmology",coverURL:"https://cdn.intechopen.com/books/images_new/7218.jpg",slug:"oct-applications-in-ophthalmology",publishedDate:"September 19th 2018",editedByType:"Edited by",bookSignature:"Michele Lanza",hash:"e3a3430cdfd6999caccac933e4613885",volumeInSeries:2,fullTitle:"OCT - Applications in Ophthalmology",editors:[{id:"240088",title:"Prof.",name:"Michele",middleName:null,surname:"Lanza",slug:"michele-lanza",fullName:"Michele Lanza",profilePictureURL:"https://mts.intechopen.com/storage/users/240088/images/system/240088.png",biography:"Michele Lanza is Associate Professor of Ophthalmology at Università della Campania, Luigi Vanvitelli, Napoli, Italy. His fields of interest are anterior segment disease, keratoconus, glaucoma, corneal dystrophies, and cataracts. His research topics include\nintraocular lens power calculation, eye modification induced by refractive surgery, glaucoma progression, and validation of new diagnostic devices in ophthalmology. \nHe has published more than 100 papers in international and Italian scientific journals, more than 60 in journals with impact factors, and chapters in international and Italian books. 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